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Wolfe, K. H. & Shields, D. C. Molecular evidence for an ancient duplication of the entire yeast genome. Nature 387, 708-713
Abstract
Gene duplication is an important source of evolutionary novelty. Most duplications are of just a single gene, but Ohno proposed that whole-genome duplication (polyploidy) is an important evolutionary mechanism. Many duplicate genes have been found in Saccharomyces cerevisiae, and these often seem to be phenotypically redundant. Here we show that the arrangement of duplicated genes in the S. cerevisiae genome is consistent with Ohno's hypothesis. We propose a model in which this species is a degenerate tetraploid resulting from a whole-genome duplication that occurred after the divergence of Saccharomyces from Kluyveromyces. Only a small fraction of the genes were subsequently retained in duplicate (most were deleted), and gene order was rearranged by many reciprocal translocations between chromosomes. Protein pairs derived from this duplication event make up 13% of all yeast proteins, and include pairs of transcription factors, protein kinases, myosins, cyclins and pheromones. Tetraploidy may have facilitated the evolution of anaerobic fermentation in Saccharomyces.
... Analysis of YFL041W-A shows that is has similarity to the C-terminal end of YLR070C (XYL2). In S. paradoxus strains N44 and CBS432, YFL041W-A is a full-length paralog of YLR070C (XYL2), and they are a WGD pair of genes (Philippsen et al. 1997, Wolfe andShields 1997). Both dubious hypothetical gene 610-snap_masked-2999-BGP_1 and dubious gene YFL041W-A overlap the S. paradoxus gene, but in different reading frames. ...
... While in most cases one gene was lost from pairs of genes resulting from the whole genome duplication (Philippsen et al. 1997, Wolfe andShields 1997), some 600 pairs of duplicate genes remain from that event in the ancestry of S. cerevisiae. ...
Examination of the genome sequence of Saccharomyces cerevisiae strain S288c and 93 additional diverse strains allows identification of the 5873 genes that make up the core set of genes in this species and gives a better sense of the organization and plasticity of this genome. S. cerevisiae strains each contain dozens to hundreds of strain specific genes. In addition to a variable content of retrotransposons, some strains contain a novel transposable element, Ty7. Examination further shows that some annotated putative protein coding genes are likely artifacts. We propose altering approximately 5% of the current annotations in the widely used reference strain S288c. Potential null alleles are common and found in all 94 strains examined, with these potential null alleles typically containing a single stop codon or frameshift. There are also gene remnants, pseudogenes, and variable arrays of genes. Among the core genes there are now only 373 protein coding genes of unknown function, classified as uncharacterized in the Saccharomyces Genome Database. This work suggests that there is a role for carefully edited and annotated genome sequences in understanding the genome organization and content of a species. We propose that gene remnants be added to the repertoire of features found in the S. cerevisiae genome, and likely other fungal species.
... Additionally, when compared with both S. cerevisiae strains (S288C and EC1118) K. aerobia shared more orthologous gene clusters than K. servazzii (Figs 3b and 4b). Lastly, K. aerobia exhibited the highest diversity of orthologous gene clusters out of the three species, which could be explained as the result of genetic divergence and domestication events [22,72] (Figs 3b and 4b). ...
... The presence of two genes in Saccharomyces (sensu stricto) species and only one in closely and distantly related species (noted above) may be the result of WGD during the evolution of ascomycete yeasts. The genus Kazachstania, along with several genera in the family Saccharomycetaceae (Saccharomyces, Nakaseomyces and Tetrapisispora) went through a WGD event (known as the post-WGD clade), which resulted in differential gene loss and gene duplications (the latter being referred to as ohnologues) [72,75,76]. Though ATF1 and ATF2 have similar functions, it is expected that only one orthologue is in pre-WGD species (L. ...
Kazachstania aerobia and Kazachstania servazzii can affect wine aroma by increasing acetate ester concentrations, most remarkably phenylethyl acetate and isoamyl acetate. The genetic basis of this is unknown, there being little to no sequence data available on the genome architecture. We report for the first time the near-complete genome sequence of the two species using long-read (PacBio) sequencing (K. aerobia 20 contigs, one scaffold; and K. servazzii 22 contigs, one scaffold). The annotated genomes of K. aerobia (12.5 Mb) and K. servazzii (12.3 Mb) were compared to Saccharomyces cerevisiae genomes (laboratory strain S288C and wine strain EC1118). Whilst a comparison of the two Kazachstania spp. genomes revealed few differences between them, divergence was evident in relation to the genes involved in ester biosynthesis, for which gene duplications or absences were apparent. The annotations of these genomes are valuable resources for future research into the evolutionary biology of Kazachstania and other yeast species (comparative genomics) as well as understanding the metabolic processes associated with alcoholic fermentation and the production of secondary 'aromatic' metabolites (transcriptomics, proteomics and metabolomics).
... The lineage that gave rise to S. cerevisiae underwent a whole genome duplication (WGD) event-a rare phenomenon whereby the entire genetic content of an ancestral cell was effectively doubled sometime after the split from the Kluyveromyces lineage, which took place approximately 150 million years ago [61,62]. This WGD was followed by the loss of most of the duplicates and evolutionary divergence between many of those that were retained. ...
... This WGD was followed by the loss of most of the duplicates and evolutionary divergence between many of those that were retained. The number of protein-coding open reading frames retained revealed that 13% of the duplicated genes from this event had been maintained, while the rest were lost [61]. An analysis of the effects of the WGD on the prevalence of functionally clustered metabolic genes within the ribosomal protein and RRB genes in S. cerevisiae determined that this genetic event had a negligible effect on the formation of functional clusters within these gene families [55]. ...
Transcriptional regulation is vital for organismal survival, with many layers and mechanisms collaborating to balance gene expression. One layer of this regulation is genome organization, specifically the clustering of functionally related, co-expressed genes along the chromosomes. Spatial organization allows for position effects to stabilize RNA expression and balance transcription, which can be advantageous for a number of reasons, including reductions in stochastic influences between the gene products. The organization of co-regulated gene families into functional clusters occurs extensively in Ascomycota fungi. However, this is less characterized within the related Basidiomycota fungi despite the many uses and applications for the species within this clade. This review will provide insight into the prevalence, purpose, and significance of the clustering of functionally related genes across Dikarya, including foundational studies from Ascomycetes and the current state of our understanding throughout representative Basidiomycete species.
... While mammalian cells harbor one mTOR protein that assembles into either complex, S. cerevisiae have two, Tor1 and Tor2 (76). This is likely due to whole genome duplication, a significant evolutionary event that led to the generation of multiple copies of preexisting proteins (80). While Tor1 assembles into TORC1, Tor2 may assemble into both TORC1 and TORC2 (76,81). ...
Saccharomyces cerevisiae respond to mating pheromone through the GPCRs Ste2 and Ste3, which promote growth of a mating projection in response to ligand binding. This commitment to mating is nutritionally and energetically taxing, and so we hypothesized that the cell may suppress mating signaling during starvation. We set out to investigate negative regulators of the mating pathway in nutritionally depleted environments. Here, we report that nutrient deprivation led to loss of Ste2 from the plasma membrane. Recapitulating this effect with nitrogen starvation led us to hypothesize that it was due to TORC1 signaling. Rapamycin inhibition of TORC1 impacted membrane levels of all yeast GPCRs. Inhibition of TORC1 also dampened mating pathway output. Deletion analysis revealed that TORC1 repression leads to α-arrestin-directed CME through TORC2-Ypk1 signaling. We then set out to determine whether major downstream effectors of the TOR complexes also downregulate pathway output during mating. We found that autophagy contributes to pathway downregulation through analysis of strains lacking ATG8 . We also show that Ypk1 significantly reduced pathway output. Thus, both autophagy machinery and TORC2-Ypk1 signaling serve as attenuators of pheromone signaling during mating. Altogether, we demonstrate that the stress-responsive TOR complexes coordinate GPCR endocytosis and reduce the magnitude of pheromone signaling, in ligand-independent and ligand-dependent contexts.
One Sentence Summary
TOR signaling regulates the localization of all Saccharomyces cerevisiae GPCRs during starvation and suppress the mating pathway in the presence and absence of ligand.
... Although the sample size is small, the strength of the Spo11-DSBs signal within ohnologous syntenic intergenic regions also shows some conservation (r = 0.37, p = 0.021, 95%CI [0.06, 0.62]). These results extend the evolutionary scale at which the strength of the Spo11-DSB hotspots that do not rely on sequence-specific elements is conserved, the divergence between the Lachancea and Saccharomyces lineages being older than the 100 million years old Saccharomyces lineage-specific whole-genome duplication (81). ...
Meiotic recombination shows broad variations across species and along chromosomes and is often suppressed at and around genomic regions determining sexual compatibility such as mating type loci in fungi. Here, we show that the absence of Spo11-DSBs and meiotic recombination on Lakl0C-left, the chromosome arm containing the sex locus of the Lachancea kluyveri budding yeast, results from the absence of recruitment of the two chromosome axis proteins Red1 and Hop1, essential for proper Spo11-DSBs formation. Furthermore, cytological observation of spread pachytene meiotic chromosomes reveals that Lakl0C-left does not undergo synapsis. However, we show that the behavior of Lakl0C-left is independent of its particularly early replication timing and is not accompanied by any peculiar chromosome structure as detectable by Hi-C in this yet poorly studied yeast. Finally, we observed an accumulation of heterozygous mutations on Lakl0C-left and a sexual dimorphism of the haploid meiotic offspring, supporting a direct effect of this absence of meiotic recombination on L. kluyveri genome evolution and fitness. Because suppression of meiotic recombination on sex chromosomes is widely observed across eukaryotes, the mechanism for recombination suppression described here may apply to other species, with the potential to impact sex chromosome evolution.
... Our experimental system comprises a pair of duplicated motor proteins involved in endocytosis (Myo3 and Myo5), called type-1 myosins, in the model organism Saccharomyces cerevisiae. These paralogous genes originated from an ancient whole genome duplication event in ascomycetes 33 . Type-I myosins are crucial for cellular viability, with their C-terminal SH3 domains playing critical roles in protein localization and actin polymerization [34][35][36][37][38] . ...
Paralogous genes are often redundant for long periods of time before they diverge in function. While their functions are preserved, paralogous proteins can accumulate mutations that, through epistasis, could impact their fate in the future. By quantifying the impact of all single-amino acid substitutions on the binding of two myosin proteins to their interaction partners, we find that the future evolution of these proteins is highly contingent on their regulatory divergence and the mutations that have silently accumulated in their protein binding domains. Differences in the promoter strength of the two paralogs amplify the impact of mutations on binding in the lowly expressed one. While some mutations would be sufficient to non-functionalize one paralog, they would have minimal impact on the other. Our results reveal how functionally equivalent protein domains could be destined to specific fates by regulatory and cryptic coding sequence changes that currently have little to no functional impact.
... WDGs potentially enabled the successful domestication of plants [7] and are important in the fight against famine [8]. Many traces and evidence of whole genome duplications can be found in the genomes of yeast and other fungal species [5,9]. From the perspective of single cell evolution studies, WGDs are prevalent in cancer progression [10] and can lead us to the prognosis of advanced cancer stages [11] or the creation of strategies for targeted therapy [12]. ...
We present a novel problem, called MetaEC, which aims to infer gene-species assignments in a collection of partially leaf-labeled gene trees labels by minimizing the size of duplication episode clustering (EC). This problem is particularly relevant in metagenomics, where incomplete data often poses a challenge in the accurate reconstruction of gene histories. To solve MetaEC, we propose a polynomial time dynamic programming (DP) formulation that verifies the existence of a set of duplication episodes from a predefined set of episode candidates. In addition, we design a method to infer distributions of gene-species mappings. We then demonstrate how to use DP to design an algorithm that solves MetaEC. Although the algorithm is exponential in the worst case, we introduce a heuristic modification of the algorithm that provides a solution with the knowledge that it is exact. To evaluate our method, we perform two computational experiments on simulated and empirical data containing whole genome duplication events, showing that our algorithm is able to accurately infer the corresponding events.
... These patterns are commonly referred to as gene synteny. They were critical in identifying the first ancient polyploidy found in a eukaryotic genome 115 and have been used in many subsequent analyses of polyploid genomes. [116][117][118] Figure 2 illustrates the principle that a WGD, in contrast to SSDs, produces duplicate genes that preserve the gene order present in the unduplicated ancestor. ...
Gene content in genomes changes through several different processes, with gene duplication being an important contributor to such changes. Gene duplication occurs over a range of scales from individual genes to whole genomes, and the dynamics of this process can be context dependent. Still, there are rules by which genes are retained or lost from genomes after duplication, and probabilistic modeling has enabled characterization of these rules, including their context-dependence. Here, we describe the biology and corresponding mathematical models that are used to understand duplicate gene retention and its contribution to the set of biochemical functions encoded in a genome.
... In the present study, we focused on MLG1, a paralogue of PSI1. It is very likely that following an ancestral whole duplication of the genome [41][42][43], the MLG1 and PSI1 genes are present (with about 10 genes) in a conserved chromosomal environment and positioned on chromosomes IV and II, respectively [44]. In agreement, in Candida albicans, a pre-whole genome duplication yeast [45], only one protein, encoded from the C6_01300W locus, shows strong similarities to Mlg1p and Psi1p. ...
In cells, phospholipids contain acyl chains of variable lengths and saturation, features that affect their functions. Their de novo synthesis in the endoplasmic reticulum takes place via the cytidine diphosphate diacylglycerol (CDP-DAG) and Kennedy pathways, which are conserved in eukaryotes. PA is a key intermediate for all phospholipids (PI, PIPs, PS, PE, PC,
PG and CL). The de novo synthesis of PA occurs by acylation of glycerophosphate leading to the synthesis of 1-acyl lysoPA and subsequent acylation of 1-acyl lysoPA at the sn-2 position. Using membranes from Escherichia coli overexpressing MLG1, we showed that the yeast gene MLG1 encodes an acyltransferase, leading specifically to the synthesis of PA from 1-acyl lysoPA. Moreover, after their de novo synthesis, phospholipids can be remodelled by acyl exchange with one and/or two acyl chains
exchanged at the sn-1 and/or sn-2 position. Based on shotgun lipidomics of the reference and mlg1D strains, as well as biochemical assays for acyltransferase activities, we identified an additional remodelling activity for Mlg1p, namely, incorporation of palmitic acid into the sn-1 position of PS and PE. By using confocal microscopy and subcellular fractionation, we
also found that this acyltransferase is located in ER membranes associated with mitochondria, a finding that highlights the importance of these organelles in the global cellular metabolism of lipids.
... ) is a phylogenetic tree of the species from which the orthologous IDRs were taken. The star indicates a whole genome hybridization (WGH) event that occurred ∼100 million years ago ( 44 ). Two IDRs, corresponding to Msn2 and its paralog Msn4, were e xamined if present. ...
Intrinsically disordered regions (IDRs) are abundant in eukaryotic proteins, but their sequence-function relationship remains poorly understood. IDRs of transcription factors (TFs) can direct promoter selection and recruit coactivators, as shown for the budding yeast TF Msn2. To examine how IDRs encode both these functions, we compared genomic binding specificity, coactivator recruitment, and gene induction amongst a large set of designed Msn2-IDR mutants. We find that both functions depend on multiple regions across the > 600AA IDR. Yet, transcription activity was readily disrupted by mutations that showed no effect on the Msn2 binding specificity. Our data attribute this differential sensitivity to the integration of a relaxed, composition-based code directing binding specificity with a more stringent, motif-based code controlling the recruitment of coactivators and transcription activity. Therefore, Msn2 utilizes interwoven sequence grammars for encoding multiple functions, suggesting a new IDR design paradigm of potentially general use.
... Nevertheless, from an evolutionary point of view, this species represents an outlier since it is more linked to S. cerevisiae than to other Candida species. These two species in fact belong to the same Saccharomycetaceae clade which is characterized using the classic genetic code (Mühlhausen & Kollmar, 2014)-in contrast to the Candida CTG clade, in which CUG encodes the amino acid serine instead of leucine (Santos et al., 2011) and both have a duplicated genome as a result of the inheritance of an ancient common ancestor (Wolfe & Shields, 1997). Along with C. glabrata, C. krusei is the other clinically isolated species not included in the CTG clade, but little is known about the virulence mechanisms of this species, although the number of nosocomial infections has increased in recent years (G omez-Gaviria & Mora-Montes, 2020). ...
Fungi are the cause of more than a billion infections in humans every year, although their interactions with the host are still neglected compared to bacteria. Major systemic fungal infections are very unusual in the healthy population, due to the long history of coevolution with the human host. Humans are routinely exposed to environmental fungi and can host a commensal mycobiota, which is increasingly considered as a key player in health and disease. Here, we review the current knowledge on host‐fungi coevolution and the factors that regulate their interaction. On one hand, fungi have learned to survive and inhabit the host organisms as a natural ecosystem, on the other hand, the host immune system finely tunes the response toward fungi. In turn, recognition of fungi as commensals or pathogens regulates the host immune balance in health and disease. In the human gut ecosystem, yeasts provide a fingerprint of the transient microbiota. Their status as passengers or colonizers is related to the integrity of the gut barrier and the risk of multiple disorders. Thus, the study of this less known component of the microbiota could unravel the rules of the transition from passengers to colonizers and invaders, as well as their dependence on the innate component of the host's immune response.
This article is categorized under: Infectious Diseases > Environmental Factors
Immune System Diseases > Environmental Factors
Infectious Diseases > Molecular and Cellular Physiology
... In yeast, since WGD occurred around the time of the emergence of fruiting plants (Wolfe and Shields 1997), changes to the metabolic milieu may have exerted selective pressures for paralog retention. To account for such effects, carrying out the screening under different environmental conditions would be necessary to reveal environment-specific paralog responses. ...
Gene duplication is common across the tree of life, including yeast and humans, and contributes to genomic robustness. In this study, we examined changes in the subcellular localization and abundance of proteins in response to the deletion of their paralogs originating from the whole-genome duplication event, which is a largely unexplored mechanism of functional divergence. We performed a systematic single-cell imaging analysis of protein dynamics and screened subcellular redistribution of proteins, capturing their localization and abundance changes, providing insight into forces determining paralog retention. Paralogs showed dependency, whereby proteins required their paralog to maintain their native abundance or localization, more often than compensation. Network feature analysis suggested the importance of functional redundancy and rewiring of protein and genetic interactions underlying redistribution response of paralogs. Translation of non-canonical protein isoform emerged as a novel compensatory mechanism. This study provides new insights into paralog retention and evolutionary forces that shape genomes.
... WDGs potentially enabled the successful domestication of plants [7] and are important in the őght against famine [8]. Many traces and evidence of whole genome duplications can be found in the genomes of yeast and other fungal species [5,9]. From the perspective of single cell evolution studies, WGDs are prevalent in cancer progression [10] and can lead us to the prognosis of advanced cancer stages [11] or the creation of strategies for targeted therapy [12]. ...
We present a novel problem, called MetaEC, which aims to infer gene-species assignments in a collection of gene trees with missing labels by minimizing the size of duplication episode clustering (EC). This problem is particularly relevant in metagenomics, where incomplete data often poses a challenge in the accurate reconstruction of gene histories. To solve MetaEC, we propose a polynomial time dynamic programming (DP) formulation that verifies the existence of a set of duplication episodes from a predefined set of episode candidates. In addition, we design a method to infer distributions of gene-species mappings. We then demonstrate how to use DP to design an algorithm that solves MetaEC. Although the algorithm is exponential in the worst case, we introduce a heuristic modification of the algorithm that provides a solution with the knowledge that it is exact. To evaluate our method, we perform two computational experiments on simulated and empirical data containing whole genome duplication events, showing that our algorithm is able to accurately infer the corresponding events.
... Gene duplication is a major evolutionary mechanism that provides raw material for generating genes with novel or modified physiological roles [1,2]. Phylogenomic studies have shown that in the ancestry of a clade of Saccharomycotina, including Saccharomyces cerevisiae and other related yeasts (post-whole genome duplication species, WGD), the occurrence of an interspecies hybridization event resulted in genome duplication [3,4]. Selective retention and sub-functionalization of gene pairs derived from the hybrid ancestor have led to the functional divergence of two paralogous copies [5][6][7][8] or to the neo-functionalization of one of the copies. ...
In Saccharomyces cerevisiae, the transcriptional repressor Nrg1(Negative Regulator of Glucose-repressed genes) and the β-Ziptranscription factor Rtg3 (ReTroGrade regulation) mediate glucose repression and signaling from the mitochondria to the nucleus, respectively. Here, we show a novel function of these, two proteins, in which alanine promotes the formation of a chimeric Nrg1/Rtg3 regulator that represses the ALT2 gene (encoding an alanine transaminase paralog of unknown function). An NRG1/NRG2 paralogous pair, resulting from a post-wide genome small-scale duplication event, ispresent in the Saccharomyces genus. Neo-functionalization of only one paralog resulted in the ability of Nrg1 to interact with Rtg3. Both nrg1Δ and rtg3Δ single mutant strains were unable to use ethanol and showed a typical petite (small) phenotype on glucose. Neither of the wild-type genes complemented the petite phenotype, suggesting irreversible mitochondrial DNA damage in these mutants. Neither nrg1Δ nor rtg3Δ mutant strains expressed genes encoded by any of the five polycistronic units transcribed from mitochondrial DNA in S. cerevisiae. This, and the direct measurement of the mitochondrial DNA gene complement, confirmed that irreversible damage of the mitochondrial DNA occurred in both mutant strains, which is consistent with the essential role of the chimeric Nrg1/Rtg3 regulator in mitochondrial DNA maintenance.
... These patterns are commonly referred to as gene synteny. They were critical in identifying the first ancient polyploidy found in a eukaryotic genome 113 and have been used in many subsequent analyses of polyploid genomes. [114][115][116] Figure 2 illustrates the principle that a genome duplication, in contrast to single-gene duplications, produces duplicated genes that preserve the gene order present in the unduplicated ancestor. ...
Gene content in genomes changes through several different processes, with gene duplication being an important contributor to such changes. Gene duplication occurs over a range of scales from individual genes to whole genomes, and the dynamics of this process can be context dependent. Still, there are rules by which genes are retained or lost from genomes after duplication, and probabilistic modeling has enabled characterization of these rules, including their context-dependence. Here, we describe the biology and corresponding mathematical models that are used to understand duplicate gene retention and its contribution to the set of biochemical functions encoded in a genome.
... A common problem is the existence of reads that map to multiple locations in the genome during the alignment step of these workflows 16 . These duplicated regions might result from a variety of events, such as whole genome duplication 17,18 , recombination 19 , retro-transposition 20 and gene duplication 21 . Multi-mapping reads must be addressed with caution during genomics and transcriptomics analysis, as they can confound gene quantification and make genome annotation more difficult. ...
There has been a dramatic increase in the identification of non-conical translation and a significant expansion of the protein-coding genome and proteome. Among the strategies used to identify novel small ORFs (smORFs), Ribosome profiling (Ribo-Seq) is the gold standard for the annotation of novel coding sequences by reporting on smORF translation. In Ribo-Seq, ribosome-protected footprints (RPFs) that map to multiple sites in the genome are computationally removed since they cannot unambiguously be assigned to a specific genomic location, or to a specific transcript in the case of multiple isoforms. Furthermore, RPFs necessarily result in short (25-34 nucleotides) reads, increasing the chance of ambiguous and multi-mapping alignments, such that smORFs that reside in these regions cannot be identified by Ribo-Seq. Here, we show that the inclusion of proteogenomics to create a Ribosome Profiling and Proteogenomics Pipeline (RP3) bypasses this limitation to identify a group of microprotein-encoding smORFs that are missed by current Ribo-Seq pipelines. Moreover, we show that the microproteins identified by RP3 have different sequence compositions from Ribo-Seq only pipelines, which can affect proteomics identification. In aggregate, the creation of RP3 maximizes the detection and confidence of protein-encoding smORFs and microproteins.
... In this study, two foxl2 paralogs, foxl2 and foxl2l, were firstly identified and named in the spotted knifejaw genome. In vertebrates, transcription factors, ribosomal proteins, cyclins, and kinases are more frequently duplicated during the WGD process [43,44]. As shown in Figure 1, foxl2 and foxl2l clustered into one clade, while foxl1 and foxl3 clustered into another clade, indicating that the duplicated transcription factor, foxl2l, may originated from the WGD, but not from the other evolutionary events. ...
As a member of the forkhead box L gene family, foxl2 plays a significant role in gonadal development and the regulation of reproduction. During the evolution of deuterostome, whole genome duplication (WGD)-enriched lineage diversifications and regulation mechanisms occurs. However, only limited research exists on foxl2 duplication in teleost or other vertebrate species. In this study, two foxl2 paralogs, foxl2 and foxl2l, were identified in the transcriptome of spotted knifejaw (Oplegnathus punctatus), which had varying expressions in the gonads. The foxl2 was expressed higher in the ovary, while foxl2l was expressed higher in the testis. Phylogenetic reconstruction, synteny analysis, and the molecular evolution test confirmed that foxl2 and foxl2l likely originated from the first two WGD. The expression patterns test using qRT-PCR and ISH as well as motif scan analysis revealed evidence of potentially functional divergence between the foxl2 and foxl2l paralogs in spotted knifejaw. Our results indicate that foxl2 and foxl2l may originate from the first two WGD, be active in transcription, and have undergone functional divergence. These results shed new light on the evolutionary trajectories of foxl2 and foxl2l and highlights the need for further detailed functional analysis of these two duplicated paralogs.
... While some hypothesized ancient whole-genome duplications are controversial (e.g., Abbasi 2010), it is clear that taxonomically important lineages including angiosperms, teleosts, and yeast experienced them (e.g., Wolfe and Shields 1997; Van de Peer et al. 2009, 2010Vanneste et al. 2014). For these lineages, genes that are now single copy may have had ancestral paralogs. ...
Following a duplication, the resulting paralogs tend to diverge. While mutation and natural selection can accelerate this process, they can also slow it. Here, we quantify the paralog homogenization that is caused by point mutations and interlocus gene conversion. Among 164 duplicated teleost genes, the median percentage of post-duplication codon substitutions that arise from interlocus gene conversion rather than point mutation is estimated to be between 7% and 8%. By differentiating between the nonsynonymous codon substitutions that homogenize the protein sequences of paralogs and the non-homogenizing nonsynonymous substitutions, we estimate the homogenizing nonsynonymous rates to be higher for 163 of the 164 teleost data sets as well as for all 14 data sets of duplicated yeast ribosomal protein-coding genes that we consider. For all 14 yeast data sets, the estimated homogenizing nonsynonymous rates exceed the synonymous rates.
... These genera identified as consistent facultative anaerobes comprise the post-whole genome duplication lineage of the Saccharomycetaceae (Kellis et al., 2004;Marcet-Houben & Gabaldón, 2015;Shen et al., 2018;Wolfe & Shields, 1997). ...
Humans rely on the ability of budding yeasts to grow without oxygen in industrial scale fermentations that produce beverages, foods, and biofuels. Oxygen is deeply woven into the energy metabolism and biosynthetic capabilities of budding yeasts. While diverse ecological habitats may provide wide varieties of different carbon and nitrogen sources for yeasts to utilize, there is no direct substitute for molecular oxygen, only a range of availability. Understanding how a small subset of budding yeasts evolved the ability to grow without oxygen could expand the set of useful species in industrial scale fermentations as well as provide insight into the cryptic field of yeast ecology. However, we still do not yet appreciate the full breadth of species that can growth without oxygen, what genes underlie this adaptation, and how these genes have evolved.
... For instance, vertebrates have experienced two rounds of WGD early in their evolution (Dehal and Boore 2005;Van de Peer et al. 2010;Nakatani et al. 2021), with an additional WGD event shared by all teleosts (Amores et al. 1998;Taylor et al. 2003). The genomes of several yeasts have also undergone ancient WGD events (Wolfe and Shields 1997). However, WGD events have been most abundant in plants, and they are thought to have contributed to the radiation of important plant families (Schranz et al. 2012;Tank et al. 2015;Landis et al. 2018), to increased diversity (Ren et al. 2018), and to survival in stressful times ; Van de Peer et al. 2021). ...
Angiosperms have a complex history of whole-genome duplications (WGDs), with varying numbers and ages of WGD events across clades. These WGDs have greatly affected the composition of plant genomes due to the biased retention of genes belonging to certain functional categories following their duplication. In particular, regulatory genes and genes encoding proteins that act in multiprotein complexes have been retained in excess following WGD. Here, we inferred protein-protein interaction (PPI) networks and gene regulatory networks (GRNs) for seven well-characterized angiosperm species and explored the impact of both WGD and small-scale duplications (SSDs) in network topology by analyzing changes in frequency of network motifs. We found that PPI networks are enriched in WGD-derived genes associated with dosage-sensitive intricate systems, and strong selection pressures constrain the divergence of WGD-derived genes at the sequence and PPI levels. WGD-derived genes in network motifs are mostly associated with dosage-sensitive processes, such as regulation of transcription and cell cycle, translation, photosynthesis, and carbon metabolism, whereas SSD-derived genes in motifs are associated with response to biotic and abiotic stress. Recent polyploids have higher motif frequencies than ancient polyploids, whereas WGD-derived network motifs tend to be disrupted on the longer term. Our findings demonstrate that both WGD and SSD have contributed to the evolution of angiosperm GRNs, but in different ways, with WGD events likely having a more significant impact on the short-term evolution of polyploids.
... Gene duplication is an evolutionary process in which genetic diversity and new functions are generated via whole-genome duplication (WGD) events or smaller-scale, single-gene or single-base duplications [1,2], the occurrence of which in a gene results in two genes that cannot be functionally distinguished from each other. In the evolutionary history of plants, animals, and fungi, gene duplication events have occurred ubiquitously across kingdoms [3][4][5][6]. In comparison with other eukaryotic genomes, plants typically have a higher rate of evolution, which entails continuous increases in their genomic diversity [7,8]. ...
Gene duplication is a universal biological phenomenon that drives genomic variation and diversity, plays a crucial role in plant evolution, and contributes to innovations in genetic engineering and crop development. Duplicated genes participate in the emergence of novel functionality, such as adaptability to new or more severe abiotic stress resistance. Future crop research will benefit from advanced, mechanistic understanding of the effects of gene duplication, especially in the development and deployment of high-performance, stress-resistant, elite wheat lines. In this review, we summarize the current knowledge of gene duplication in wheat, including the principle of gene duplication and its effects on gene function, the diversity of duplicated genes, and how they have functionally diverged. Then, we discuss how duplicated genes contribute to abiotic stress response and the mechanisms of duplication. Finally, we have a future prospects section that discusses the direction of future efforts in the short term regarding the elucidation of replication and retention mechanisms of repetitive genes related to abiotic stress response in wheat, excellent gene function research, and practical applications.
... Polyploidization and hybridization are closely interrelated processes (Albertin and Marullo 2012) and the polyploidy in fungi could evoke the WGD that occurred in Saccharomyces lineage about 100 Mya ago (Wolfe and Shields 1997). As confirmed above, the cell fusion or hybridization of two different genomes from the different ancestors of A. melanogenum caused the WGD in the TN3-1 strain. ...
Aureobasidium melanogenum TN3-1 strain and A. melanogenum P16 strain were isolated from the natural honey and the mangrove ecosystem, respectively. The former can produce much higher pullulan from high concentration of glucose than the latter. In order to know what happened to their genomes, the PacBio sequencing and Hi-C technologies were used to create the first high-quality chromosome-level reference genome assembly of A. melanogenum TN3-1 (51.61 Mb) and A. melanogenum P16 (25.82 Mb) with the contig N50 of 2.19 Mb and 2.26 Mb, respectively. Based on the Hi-C results, a total of 93.33% contigs in the TN3-1 strain and 92.31% contigs in the P16 strain were anchored onto 24 and 12 haploid chromosomes, respectively. The genomes of the TN3-1 strain had two subgenomes A and B. Synteny analysis showed that the genomic contents of the two subgenomes were asymmetric with many structural variations. Intriguingly, the TN3-1 strain was revealed as a recent hybrid/fusion between the ancestor of A. melanogenum CBS105.22/CBS110374 and the ancestor of another unidentified strain of A. melanogenum similar to P16 strain. We estimated that the two ancient progenitors diverged around 18.38 Mya and merged around 10.66–9.98 Mya. It was found that in the TN3-1 strain, telomeres of each chromosome contained high level of long interspersed nuclear elements (LINEs), but had low level of the telomerase encoding gene. Meanwhile, there were high level of transposable elements (TEs) inserted in the chromosomes of the TN3-1 strain. In addition, the positively selected genes of the TN3-1 strain were mainly enriched in the metabolic processes related to harsh environmental adaptability. Most of the stress-related genes were found to be related to the adjacent LTRs, and the glucose derepression was caused by the mutation of the Glc7-2 in the Snf-Mig1 system. All of these could contribute to its genetic instability, genome evolution, high stress resistance, and high pullulan production from glucose.
... It is possible that in bench-top trials, the reduction in sugar concentration was enough to trigger a metabolic shift in non-Saccharomyces species that favored sugar respiration, which would explain the higher biomass yield and the lower ethanol production we observed. Furthermore, S. cerevisiae is a post-WGD (Whole Genome Duplication) yeast, unlike H. vineae and M. pulcherrima (Wolfe and Shields, 1997;Shen et al., 2016). The increased glycolytic enzyme content in post-WGD yeasts favors sugar fermentation, since the increase in pyruvate concentration promotes its flux to acetaldehyde via pyruvate decarboxylase (Conant and Wolfe, 2007). ...
The use of non- Saccharomyces yeasts as starters in winemaking has increased exponentially in the last years. For instance, non-conventional yeasts have proven useful for the improvement of the organoleptic profile and biocontrol. Active dry yeast starter production has been optimized for Saccharomyces cerevisiae , which may entail problems for the propagation of non- Saccharomyces yeasts. This work shows that the poor growth of Hanseniaspora vineae and Metschnikowia pulcherrima in molasses is related to a deficient sucrose consumption, linked to their low invertase activity. In order to address this issue, simple modifications to the cultivation media based hydrolysis and the reduction of sucrose concentration were performed. We performed biomass propagation simulations at a bench-top and bioreactor scale. The results show that cultivation in a hexose-based media improved biomass production in both species, as it solves their low invertase activity. The reduction in sugar concentration promoted a metabolic shift to a respiratory metabolism, which allowed a higher biomass yield, but did not improve total biomass production, due to the lower sugar availability. To evaluate the technological performance of these adaptations, we performed mixed grape juice fermentations with biomass produced in such conditions of M. pulcherrima and S. cerevisiae. The analysis of wines produced revealed that the different treatments we have tested did not have any negative impact on wine quality, further proving their applicability at an industrial level for the improvement of biomass production.
... However, we cannot rule out the possibility of loss in this species. Loss of one of the copies due to accumulation of random mutations is a common fate among duplicated genes (Ohno 1970;Wolfe and Shields 1997;Inoue et al. 2015). Moreover, in D. melanogaster, the knockdown of this duplicate has no effect on the individual's viability Cheng et al. 2012). ...
Odysseus (OdsH) was the first gene described in Drosophila related to speciation and hybrid sterility. This gene was first described in the melanogaster subgroup and more specifically in the sterile hybrids from crosses between D. mauritiana and D. simulans. Its origin is attributed to the duplication of the gene unc-4, which would have occurred in the ancestor of the subgenus Sophophora. By using a much larger sample of Drosophila species, we showed that contrary to what has been previously proposed, OdsH origin occurred approximately 62 million years ago (Mya). Then, OdsH have experienced rapid neofunctionalization in male reproductive tracts, evidenced by its evolutionary rates, expression and transcription factor binding sites. Furthermore, the analysis of the OdsH peptide sequence allowed the identification of mutations in the DNA- and protein-binding domains of D. mauritiana that could result in incompatibility with genomes from other species. We then explored the expression of OdsH in the spermatocytes of D. arizonae and D. mojavensis, a pair of recently diverged sister species with incomplete reproductive isolation and expected to find the involvement of OdsH in hybrid sterility. Our data indicated that OdsH expression is not atypical in male-sterile hybrids from these species. In conclusion, we have demonstrated that the origin of OdsH occurred earlier than previously proposed and that its neofunctionalization in male sexual functions occurred rapidly after its origin. Our results also suggested that its role as a speciation gene, as in the melanogaster subgroup of species, may be restricted to this specific taxon.
... Ancient WGD events have occurred across the tree of life and are especially well studied in plants [1][2][3][4] , yeast 5,6 , and vertebrates [7][8][9][10][11][12][13][14][15][16][17][18] . These events are often hypothesised to have facilitated evolutionary success through provision of the raw genetic materials for phenotypic innovation and species diversification 1,[19][20][21][22][23] . ...
Whole genome duplication (WGD) is a dramatic evolutionary event generating many new genes and which may play a role in survival through mass extinctions. Paddlefish and sturgeon are sister lineages that both show genomic evidence for ancient WGD. Until now this has been interpreted as two independent WGD events due to a preponderance of duplicate genes with independent histories. Here we show that although there is indeed a plurality of apparently independent gene duplications, these derive from a shared genome duplication event occurring well over 200 million years ago, likely close to the Permian-Triassic mass extinction period. This was followed by a prolonged process of reversion to stable diploid inheritance (rediploidization), that may have promoted survival during the Triassic-Jurassic mass extinction. We show that the sharing of this WGD is masked by the fact that paddlefish and sturgeon lineage divergence occurred before rediploidization had proceeded even half-way. Thus, for most genes the resolution to diploidy was lineage-specific. Because genes are only truly duplicated once diploid inheritance is established, the paddlefish and sturgeon genomes are thus a mosaic of shared and non-shared gene duplications resulting from a shared genome duplication event.
... While WGD events are relatively common in plants, such as Arabidopsis, and have also been observed in the yeast Saccharomyces [158,159], identifying WGD pairs or quartets in vertebrates is more difficult. It is by now widely accepted that two rounds of WGD happened at the origin of the vertebrate lineage about 500-550 millions of years ago [160,161] (Figure 2). ...
The integrity of the genome is crucial for the survival of all living organisms. However, genomes need to adapt to survive certain pressures and for this propose use several mechanisms to diversify. Chromosomal instability (CIN) is one of the main mechanism leading to the creation of genomic heterogeneity by altering the number of chromosomes as well as changing their structures. In this review we will discuss the different chromosomal patterns and changes observed in speciation, in evolutional biology as well as during tumor progression. By nature, human genome shows induction of diversity during gametogenesis but as well during tumorigenesis that can conclude in drastic changes such as whole genome doubling to more discrete changes as indels as well as the recent discovered complex chromosomal rearrangement chromothripsis. More importantly, changes observed during speciation are strikingly similar to the genomic evolution observed during tumor progression and resistance to therapy. The different origins of CIN will be treated as the importance of double strand breaks (DSB) or the consequences of micronuclei. We will also explain the mechanisms behind the controlled DSBs and recombination of homologous chromosomes observed during meiosis, to explain how errors lead to similar pattern observed during tumorigenesis. Then, we will also list several diseases associated to CIN resulting in fertility issue, miscarriage, genetic rare diseases and cancer. Understanding better chromosomal instability as a whole is primordial for the understanding of mechanisms leading to tumor progression.
... While WGD events are relatively common in plants, such as Arabidopsis, and have also been observed in the yeast Saccharomyces [217,218], identifying WGD pairs or quartets in vertebrates is more difficult. It is now widely accepted that two rounds of WGD happened at the origin of the vertebrate lineage about 500-550 million years ago [219,220] (Figure 2). ...
Simple Summary
The experimental/pathological observation of genome chaos (including massive and large-scale translocations, chromothripsis, and polyploidy cancer cells) highlighted the importance of genome reorganization in evolution. Recent advances in sequencing and bioinformatic analysis have highlighted such chromosomal diversity. The evolution of the genome has been studied in the field of macroevolution and speciation as well as in the context of cancer and tumor progression. Evolution is inherent to adaptation to the environment and preparing for future pressure to initiate survival. Human cells are plastic, and several mechanisms are involved in sporadic timing in view of generating genomic diversity under normal conditions, such as during gametogenesis or during pathology like cancer. Interestingly, patterns of chromosomal instability are strikingly similar in evolution and in cancer. Here we will discuss some events leading to several varieties of chromosomal patterns, from cancer to speciation, and discuss the disease associated with chromosomal instability.
Abstract
The integrity of the genome is crucial for the survival of all living organisms. However, genomes need to adapt to survive certain pressures, and for this purpose use several mechanisms to diversify. Chromosomal instability (CIN) is one of the main mechanisms leading to the creation of genomic heterogeneity by altering the number of chromosomes and changing their structures. In this review, we will discuss the different chromosomal patterns and changes observed in speciation, in evolutional biology as well as during tumor progression. By nature, the human genome shows an induction of diversity during gametogenesis but as well during tumorigenesis that can conclude in drastic changes such as the whole genome doubling to more discrete changes as the complex chromosomal rearrangement chromothripsis. More importantly, changes observed during speciation are strikingly similar to the genomic evolution observed during tumor progression and resistance to therapy. The different origins of CIN will be treated as the importance of double-strand breaks (DSBs) or the consequences of micronuclei. We will also explain the mechanisms behind the controlled DSBs, and recombination of homologous chromosomes observed during meiosis, to explain how errors lead to similar patterns observed during tumorigenesis. Then, we will also list several diseases associated with CIN, resulting in fertility issues, miscarriage, rare genetic diseases, and cancer. Understanding better chromosomal instability as a whole is primordial for the understanding of mechanisms leading to tumor progression.
... These results suggest that the preservation of specific subfamilies may vary among species with different evolutionary histories. Several genomic evolutionary models have been proposed in model species on the basis of comparative genomic analysis (Wolfe and Shields, 1997;Moore and Purugganan, 2003;Hurley et al., 2005). If duplicated genes are retained, they tend to diverge in their regulatory and coding regions, and differences in coding regions, especially those that alter gene function, may cause amino acid changes or substitutions or changes in exon/intron structure (Xu et al., 2012). ...
Background:
Pineapple is the only commercially grown fruit crop in the Bromeliaceae family and has significant agricultural, industrial, economic, and ornamental value. GRF (growth-regulating factor) proteins are important transcription factors that have evolved in seed plants (embryophytes). They contain two conserved domains, QLQ (Gln, Leu, Gln) and WRC (Trp, Arg, Cys), and regulate multiple aspects of plant growth and stress response, including floral organ development, leaf growth, and hormone responses. The GRF family has been characterized in a number of plant species, but little is known about this family in pineapple and other bromeliads.
Main discoveries:
We identified eight GRF transcription factor genes in pineapple, and phylogenetic analysis placed them into five subfamilies (I, III, IV, V, VI). Segmental duplication appeared to be the major contributor to expansion of the AcGRF family, and the family has undergone strong purifying selection during evolution. Relative to that of other gene families, the gene structure of the GRF family showed less conservation. Analysis of promoter cis-elements suggested that AcGRF genes are widely involved in plant growth and development. Transcriptome data and qRT-PCR results showed that, with the exception of AcGRF5, the AcGRFs were preferentially expressed in the early stage of floral organ development and AcGRF2 was strongly expressed in ovules. Gibberellin treatment significantly induced AcGRF7/8 expression, suggesting that these two genes may be involved in the molecular regulatory pathway by which gibberellin promotes pineapple fruit expansion.
Conclusion:
AcGRF proteins appear to play a role in the regulation of floral organ development and the response to gibberellin. The information reported here provides a foundation for further study of the functions of AcGRF genes and the traits they regulate.
... Because POInT provides high quality orthology inferences that are not dependent on gene trees inferred from the sequences involved, the orthology that is evident from the gene order can be contrasted with gene trees inferred from the sequences. In our case, we could show that paralogous ribosomal proteins showed evidence for very strong and recent gene conversion, such that those paralogs, created by the ancient genome duplication about one hundred million years ago [33], were more similar to each other than either was to its orthologous gene in a closely related yeast species, despite the much more recent split (a few million years) of those orthologs [31]. ...
We describe POInT browse , a web portal that gives access to the orthology inferences made for polyploid genomes with POInT, the Polyploidy Orthology Inference Tool. Ancient, or paleo-, polyploidy events are widely distributed across the eukaryotic phylogeny, and the combination of duplicated and lost duplicated genes that these polyploidies produce can confound the identification of orthologous genes between genomes. POInT uses conserved synteny and phylogenetic models to infer ortholo-gous genes between genomes with a shared polyploidy. It also gives confidence estimates for those orthology inferences. POInT browse gives both graphical and query-based access to these inferences from 12 different polyploidy events, allowing users to visualize genomic regions produced by polyploidies and perform batch queries for each polyploidy event, downloading genes trees and coding sequences for ortholo-gous genes meeting user-specified criteria. POInT browse and the associated data are online at https:// wgd. statg en. ncsu. edu.
The interplay between ribosomal protein composition and mitochondrial function is essential for sustaining energy homeostasis. Precise stoichiometric production of ribosomal proteins is crucial to maximize protein synthesis efficiency while reducing the energy costs to the cell. However, the impact of this balance on mitochondrial ATP generation, morphology and function remains unclear. Particularly, the loss of a single copy ribosomal protein gene is observed in Mendelian disorders like Diamond Blackfan Anemia and is common in somatic tumors, yet the implications of this imbalance on mitochondrial function and energy dynamics are still unclear. In this study, we investigated the impact of haploinsufficiency for four ribosomal protein genes implicated in ribosomopathy disorders ( rps-10, rpl-5, rpl-33, rps-23 ) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells. Our findings uncover significant, albeit variably penetrant, mitochondrial morphological differences across these mutants, alongside an upregulation of glutathione transferases, and SKN-1 dependent increase in oxidative stress resistance, indicative of increased ROS production. Specifically, loss of a single copy of rps-10 in C. elegans led to decreased mitochondrial activity, characterized by lower energy levels and reduced oxygen consumption. A similar reduction in mitochondrial activity and energy levels was observed in human leukemia cells with a 50% reduction in RPS10 transcript levels. Importantly, we also observed alterations in the translation efficiency of nuclear and mitochondrial electron transport chain components in response to reductions in ribosomal protein genes’ expression in both C. elegans and human cells. This suggests a conserved mechanism whereby the synthesis of components vital for mitochondrial function are adjusted in the face of compromised ribosomal machinery. Finally, mitochondrial membrane and cytosolic ribosomal components exhibited significant covariation at the RNA and translation efficiency level in lymphoblastoid cells across a diverse group of individuals, emphasizing the interplay between the protein synthesis machinery and mitochondrial energy production. By uncovering the impact of ribosomal protein haploinsufficiency on the translation efficiency of electron transport chain components, mitochondrial physiology, and the adaptive stress responses, we provide evidence for an evolutionarily conserved strategy to safeguard cellular functionality under genetic stress.
Introgression allows polyploid species to acquire new genomic content from diploid progenitors or from other unrelated diploid or polyploid lineages, contributing to genetic diversity and facilitating adaptive allele discovery. In some cases, high levels of introgression elicit the replacement of large numbers of alleles inherited from the polyploid's ancestral species, profoundly reshaping the polyploid's genomic composition. In such complex polyploids it is often difficult to determine which taxa were the progenitor species and which taxa provided additional introgressive blocks through subsequent hybridization. Here, we use population-level genomic data to reconstruct the phylogenetic history of Betula pubescens (downy birch), a tetraploid species often assumed to be of allopolyploid origin and which is known to hybridize with at least four other birch species. This was achieved by modeling of polyploidization and introgression events under the multispecies coalescent and then using an approximate Bayesian computation (ABC) rejection algorithm to evaluate and compare competing polyploidization models. We provide evidence that B. pubescens is the outcome of an autoploid genome doubling event in the common ancestor of B. pendula and its extant sister species, B. platyphylla, that took place approximately 178,000-188,000 generations ago. Extensive hybridization with B. pendula, B. nana, and B. humilis followed in the aftermath of autopolyploidization, with the relative contribution of each of these species to the B. pubescens genome varying markedly across the species' range. Functional analysis of B. pubescens loci containing alleles introgressed from B. nana identified multiple genes involved in climate adaptation, while loci containing alleles derived from B. humilis revealed several genes involved in the regulation of meiotic stability and pollen viability in plant species.
Endosomal coats incorporate membrane-binding subunits such as sorting nexin (SNX) proteins. The Saccharomyces cerevisiae SNX-BAR paralogs Vin1 and Vps5 are respective subunits of the endosomal VINE and retromer complexes whose dimerizing BAR domains are required for complex assembly and membrane association. However, a degree of promiscuity is predicted for yeast BAR-BAR pairings, and recent work has implicated the unstructured N-terminal domains of Vin1 and Vps5 in coat formation. Here, we map N-terminal signals in both SNX-BAR paralogs that contribute to the assembly and function of two distinct endosomal coats in vivo. Whereas Vin1 leverages a polybasic region and adjacent hydrophobic motif to bind Vrl1 and form VINE, the N-terminus of Vps5 interacts with the retromer subunit Vps29 at two sites, including a conserved hydrophobic pocket in Vps29 that engages other accessory proteins in humans. We also examined the sole isoform of Vps5 from the milk yeast Kluyveromyces lactis and found that ancestral yeasts may have used a nested N-terminal signal to form both VINE and retromer. Our results suggest that the specific assembly of Vps5-family SNX-BAR coats depends on inputs from unique N-terminal sequence features in addition to BAR domain coupling, expanding our understanding of endosomal coat biology.
Interspecies hybridization is prevalent in various eukaryotic lineages and plays important roles in phenotypic diversification, adaption, and speciation. To better understand the changes that occurred in the different subgenomes of a hybrid species and how they facilitated adaptation, we completed chromosome-level de novo assemblies of all 16 pairs chromosomes for a recently formed hybrid yeast, Saccharomyces bayanus strain CBS380 (IFO11022), using Nanopore MinION long-read sequencing. Characterization of S. bayanus subgenomes and comparative analysis with the genomes of its parent species, S. uvarum and S. eubayanus, provide several new insights into understanding genome evolution after a relatively recent hybridization. For instance, multiple recombination events between the two subgenomes have been observed in each chromosome, followed by loss of heterozygosity (LOH) in most chromosomes in nine chromosome pairs. In addition to maintaining nearly all gene content and synteny from its parental genomes, S. bayanus has acquired many genes from other yeast species, primarily through the introgression of S. cerevisiae, such as those involved in the maltose metabolism. In addition, the patterns of recombination and LOH suggest an allotetraploid origin of S. bayanus. The gene acquisition and rapid LOH in the hybrid genome probably facilitated its adaption to maltose brewing environments and mitigated the maladaptive effect of hybridization.
Saccharomyces cerevisiae finds an important place in industrial setup for synthesizing molecules with nutraceuticals and pharmaceuticals properties thereby serving as cellular factories. Its biomolecular pathways work on Crabtree effect and adopt “make-accumulate-consume” mechanism. Biomolecules of industrial importance derived from it is in demand and its genome editing through various RNA- and DNA-based strategies are topped to raise a capita. Among various strategies utilization of CRISPR, CRISPR-associated (Cas) systems along with SpCas9 and dCAS9 are used for designing productive and tolerant-engineered phenotypes for the enhanced production of industrially important free fatty acid, sesquiterpene lactone, kauniolide, 2 3-Butanediol, 3-hydroxypropionic acid, β-carotene, β-amyrin, santalene, ethanol, furfural etc.. Many engineered phenotypes are produced by editing through SpCas9 for the escalated synthesis of muconic acid, free fatty acids, hydrocortisone, cellobiose utilization or designed for ethanol tolerance, canavanine resistance using sgRNA components while dCAS9 is used to design phenotypes for the production of 2 3-butanediol, isoprenoids, triacylglycerols, glycerol, 3-dehydroshikimate, xylose, and violacein.
Ticks, hematophagous acari, pose a significant threat by transmitting various pathogens to their vertebrate hosts during feeding. Despite advances in tick genomics, high-quality genomes were lacking until recently, particularly in the genus Ixodes , which includes the main vectors of Lyme disease. Here, we present the complete genome sequences of four tick species, derived from a single female individual, with a particular focus on the European species Ixodes ricinus , achieving a chromosome-level assembly. Additionally, draft assemblies were generated for the three other Ixodes species, I. persulcatus, I. pacificus and I. hexagonus . The quality of the four genomes and extensive annotation of several important gene families have allowed us to study the evolution of gene repertoires at the level of the genus Ixodes and of the tick group. We have determined gene families that have undergone major amplifications during the evolution of ticks, while an expression atlas obtained for I. ricinus reveals striking patterns of specialization both between and within gene families. Notably, several gene family amplifications are associated with a proliferation of single-exon genes. The integration of our data with existing genomes establishes a solid framework for the study of gene evolution, improving our understanding of tick biology. In addition, our work lays the foundations for applied research and innovative control targeting these organisms.
Gene and genome duplications are major evolutionary forces that shape the diversity and complexity of life. However, different duplication modes have distinct impacts on gene function, expression, and regulation. Existing tools for identifying and classifying duplicated genes are either outdated or not user-friendly. Here, we present doubletrouble, an R/Bioconductor package that provides a comprehensive and robust framework for analyzing duplicated genes from genomic data. doubletrouble can detect and classify gene pairs as derived from six duplication modes (segmental, tandem, proximal, retrotransposon-derived, DNA transposon-derived, and dispersed duplications), calculate substitution rates, detect signatures of putative whole-genome duplication events, and visualize results as publication-ready figures. We applied doubletrouble to classify the duplicated gene repertoire in 822 eukaryotic genomes, which we made available through a user-friendly web interface (available at https://almeidasilvaf.github.io/doubletroubledb). doubletrouble is freely accessible from Bioconductor (https://bioconductor.org/packages/doubletrouble), and it provides a valuable resource to study the evolutionary consequences of gene and genome duplications.
Keywords: molecular evolution, comparative genomics, paralogous genes, polyploidy.
Whole genome duplications (WGDs) can be a key event in evolution, playing a role in both adaptation and speciation. While WGDs are common throughout the history of plants, only a few examples have been proposed in metazoans. Among these, recent proposals of WGD events in Chelicerates, the group of Arthropods that includes horseshoe crabs, ticks, scorpions, and spiders, include several rounds in the history of horseshoe crabs, with an additional WGD proposed in the ancestor of spiders and scorpions. However, many of these inferences are based on evidence from only a small portion of the genome (in particular, the Hox gene cluster); therefore, genome-wide inferences with broader species sampling may give a clearer picture of WGDs in this clade. Here, we investigate signals of WGD in Chelicerates using whole genomes from 17 species. We employ multiple methods to look for these signals, including gene tree analysis of thousands of gene families, comparisons of synteny, and signals of divergence among within-species paralogs. We test several scenarios of WGD in Chelicerates using multiple species trees as a backbone for all hypotheses. While we do find support for at least one WGD in the ancestral horseshoe crab lineage, we find no evidence for a WGD in the history of spiders and scorpions using any genome-scale method. This study not only sheds light on genome evolution and phylogenetics within Chelicerates, but also demonstrates how a combination of comparative methods can be used to investigate signals of ancient WGDs.
Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans . Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites revealed that the acetylation status of Isw1 K97 coordinates with its ubiquitination processes at Isw1 K113 and Isw1 K441 through modulating the interaction between Isw1 and Cdc4, an E3 ligase. Additionally, clinical isolates of C. neoformans overexpressing the degradation-resistant ISW1 K97Q allele showed impaired drug-resistant phenotypes. Collectively, our studies revealed a sophisticated acetylation-Isw1-ubiquitination regulation axis that controls multidrug resistance in C. neoformans . .
Odysseus (OdsH) was the first speciation gene described in Drosophila related to hybrid sterility in offspring of mating between D. mauritiana and D. simulans. Its origin is attributed to the duplication of the gene unc-4 in the subgenus Sophophora. By using a much larger sample of Drosophilidae species, we showed that contrary to what has been previously proposed, OdsH origin occurred 62 million years ago. Evolutionary rates, expression and transcription factor binding sites of OdsH evidence that it may have rapidly experienced neofunctionalization in male sexual functions. Furthermore, the analysis of the OdsH peptide allowed the identification of mutations of D. mauritiana that could result in incompatibility in hybrids. In order to find if OdsH could be related to hybrid sterility, beyond Sophophora, we explored the expression of OdsH in D. arizonae and D. mojavensis, a pair of sister species with incomplete reproductive isolation. Our data indicated that OdsH expression is not atypical in their male-sterile hybrids. In conclusion, we have proposed that the origin of OdsH occurred earlier than previously proposed, followed by neofunctionalization. Our results also suggested that its role as a speciation gene might be restricted to D. mauritiana and D. simulans.
Genomic instability is a hallmark of cancer, resulting in tumor genomes having large numbers of genetic aberrations, including homozygous deletions of protein coding genes. That tumor cells remain viable in the presence of such gene loss suggests high robustness to genetic perturbation. In model organisms and cancer cell lines, paralogs have been shown to contribute substantially to genetic robustness—they are generally more dispensable for growth than singletons. Here, by analyzing copy number profiles of > 10,000 tumors, we test the hypothesis that the increased dispensability of paralogs shapes tumor genome evolution. We find that genes with paralogs are more likely to be homozygously deleted and that this cannot be explained by other factors known to influence copy number variation. Furthermore, features that influence paralog dispensability in cancer cell lines correlate with paralog deletion frequency in tumors. Finally, paralogs that are broadly essential in cancer cell lines are less frequently deleted in tumors than non‐essential paralogs. Overall, our results suggest that homozygous deletions of paralogs are more frequently observed in tumor genomes because paralogs are more dispensable.
Protein-protein interactions drive many cellular processes. Some interactions are directed by Src homology 3 (SH3) domains that bind proline-rich motifs on other proteins. The evolution of the binding specificity of SH3 domains is not completely understood, particularly following gene duplication. Paralogous genes accumulate mutations that can modify protein functions and, for SH3 domains, their binding preferences. Here, we examined how the binding of the SH3 domains of two paralogous yeast type I myosins, Myo3 and Myo5, evolved following duplication. We found that the paralogs have subtly different SH3-dependent interaction profiles. However, by swapping SH3 domains between the paralogs and characterizing the SH3 domains freed from their protein context, we find that very few of the differences in interactions, if any, depend on the SH3 domains themselves. We used ancestral sequence reconstruction to resurrect the pre-duplication SH3 domains and examined, moving back in time, how the binding preference changed. Although the closest ancestor of the two domains had a very similar binding preference as the extant ones, older ancestral domains displayed a gradual loss of interaction with the modern interaction partners when inserted in the extant paralogs. Molecular docking and experimental characterization of the free ancestral domains showed that their affinity with the proline motifs is likely not the cause for this loss of binding. Taken together, our results suggest that the SH3 and its host protein could create intramolecular or allosteric interactions essential for the SH3-dependent PPIs, making domains not functionally equivalent even when they have the same binding specificity.
Variation in the chromosome numbers can arise from the erroneous mitosis or fusion and fission of chromosomes. While the mitotic errors lead to an increase or decrease in the overall chromosomal substance in the daughter cells, fission and fusion keep this conserved. Variations in chromosome numbers are assumed to be a crucial driver of speciation. For example, the members of the muntjac species are known to have very different karyotypes with the chromosome numbers varying from 2n=70+3B in the brown brocket deer to 2n=46 in the Chinese muntjac and 2n=6/7 in the Indian muntjac. The chromosomal content in the nucleus of these closely related mammals is roughly the same and various chromosome fusion and fission pathways have been suggested as the evolution process of these karyotypes. Similar trends can also be found in lepidoptera and yeast species which show a wide variation of chromosome numbers. The effect of chromosome number variation on the spindle assembly time and accuracy is still not properly addressed. We computationally investigate the effect of conservation of the total chromosomal substance on the spindle assembly during prometaphase. Our results suggest that chromosomal fusion pathways aid the microtubule-driven search and capture of the kinetochore in cells with monocentric chromosomes. We further report a comparative analysis of the site and percentage of amphitelic captures, dependence on cell shape, and position of the kinetochore in respect to chromosomal volume partitioning.
Meiotic recombination shows broad variations across species and along chromosomes, and is often suppressed at and around genomic regions determining sexual compatibility such as mating type loci in fungi. Here we show that the absence of Spo11-DSBs and meiotic recombination on Lakl0C-left, the chromosome arm containing the sex locus of the Lachancea kluyveri budding yeast, results from the absence of recruitment of the two chromosome axis proteins Red1 and Hop1, essential for proper Spo11-DSBs formation. Furthermore, cytological observation of spread pachytene meiotic chromosomes reveals that Lakl0C-left does not undergo synapsis. However, we show that the behavior of Lakl0C-left is independent of its particularly early replication timing and is not accompanied by any peculiar chromosome structure as detectable by Hi-C in this yet poorly studied yeast. Finally, we observed an accumulation of heterozygous mutations on Lakl0C-left and a sexual dimorphism of the haploid meiotic offspring, supporting a direct effect of this absence of meiotic recombination on L. kluyveri genome evolution and fitness. Because suppression of meiotic recombination on sex chromosomes is widely observed across eukaryotes, the novel mechanism for recombination suppression described here may apply to other species, with the potential to impact sex chromosome evolution.
Introgression allows polyploid species to acquire new genomic content from diploid progenitors or from other unrelated diploid or polyploid lineages, contributing to genetic diversity and facilitating adaptive allele discovery. In some cases, high levels of introgression elicit the replacement of large numbers of alleles inherited from the polyploid's ancestral species, profoundly reshaping the polyploid's genomic composition. In such complex polyploids it is often difficult to determine which taxa were the progenitor species and which taxa provided additional introgressive blocks through subsequent hybridization. Here, we use population-level genomic data to reconstruct the phylogenetic history of Betula pubescens (downy birch), a tetraploid species often assumed to be of allopolyploid origin and which is known to hybridize with at least four other birch species. This was achieved by modeling of polyploidization and introgression events under the multispecies coalescent and then using an approximate Bayesian computation (ABC) rejection algorithm to evaluate and compare competing polyploidization models. We provide evidence that B. pubescens is the outcome of an autoploid genome doubling event in the common ancestor of B. pendula and its extant sister species, B. platyphylla , that took place approximately 178,000-188,000 generations ago. Extensive hybridization with B. pendula , B. nana , and B. humilis followed in the aftermath of autopolyploidization, with the relative contribution of each of these species to the B. pubescens genome varying markedly across the species' range. Functional analysis of B. pubescens loci containing alleles introgressed from B. nana identified multiple genes involved in climate adaptation, while loci containing alleles derived from B. humilis revealed several genes involved in the regulation of meiotic stability and pollen viability in plant species.
Yeast mitochondrial genes are expressed as polycistronic transcription units that contain RNAs from different classes and show great evolutionary variability. The promoters are simple, and transcriptional control is rudimentary. Posttranscriptional mechanisms involving RNA maturation, stability, and degradation are thus the main force shaping the transcriptome and determining the expression levels of individual genes. Primary transcripts are fragmented by tRNA excision by RNase P and tRNase Z, additional processing events occur at the dodecamer site at the 3' end of protein-coding sequences. groups I and II introns are excised in a self-splicing reaction that is supported by protein splicing factors encoded by the nuclear genes, or by the introns themselves. The 3'-to-5' exoribonucleolytic complex called mtEXO is the main RNA degradation activity involved in RNA turnover and processing, supported by an auxiliary 5'-to-3' exoribonuclease Pet127p. tRNAs and, to a lesser extent, rRNAs undergo several different base modifications. This complex gene expression system relies on the coordinated action of mitochondrial and nuclear genes and undergoes rapid evolution, contributing to speciation events. Moving beyond the classical model yeast Saccharomyces cerevisiae to other budding yeasts should provide important insights into the coevolution of both genomes that constitute the eukaryotic genetic system.
Translation initiation factor 4G (eIF4G) is an integral component of the eIF4F complex which is key to translation initiation for most eukaryotic mRNAs. Many eIF4G isoforms have been described in diverse eukaryotic organisms but we currently have a poor understanding of their functional roles and whether they regulate translation in an mRNA specific manner. The yeast Saccharomyces cerevisiae expresses two eIF4G isoforms, eIF4G1 and eIF4G2, that have previously been considered as functionally redundant with any phenotypic differences arising due to alteration in eIF4G expression levels. Using homogenic strains that express eIF4G1 or eIF4G2 as the sole eIF4G isoforms at comparable expression levels to total eIF4G, we show that eIF4G1 is specifically required to mediate the translational response to oxidative stress. eIF4G1 binds the mRNA cap and remains associated with actively translating ribosomes during oxidative stress conditions and we use quantitative proteomics to show that eIF4G1 promotes oxidative stress-specific proteome changes. eIF4G1, but not eIF4G2, binds the Slf1 LARP protein which appears to mediate the eIF4G1-dependent translational response to oxidative stress. We show similar isoform specific roles for eIF4G in human cells suggesting convergent evolution of multiple eIF4G isoforms offers significant advantages especially where translation must continue under stress conditions.
This article considers scientific evidence relevant to 4 claims that are often made about the findings of research that has compared the sexes. These claims are that the sex-related differences demonstrated by empirical research are small, unusually unstable across studies, very often artifactual, and inconsistent with the content of gender stereotypes. The empirical status of these claims has been seriously weakened by the findings of numerous quantitative syntheses of research that have compared female and male behavior. This weakening of the evidence has jeopardized the feminist political agenda of using empirical research to disconfirm gender stereotypes to raise women's status. Consequently, comparing the sexes has become increasingly controversial among psychologists. To deal responsibly with the issues that have been raised, psychologists should consider the role that their research plays in discourse on the status of women in society. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Two independent pathways of transcriptional regulation that show functional homology have been identified in yeast. It has been demonstrated previously that SWI5 encodes a zinc finger DNA-binding protein whose transcription and cellular localization both are cell cycle regulated. We show that ACE2, whose zinc finger region is nearly identical to that of SWI5, shows patterns of cell cycle-regulated transcription and nuclear localization similar to those seen previously for SWI5. Despite their similarities, SWI5 and ACE2 function in separate pathways of transcriptional regulation. SWI5 is a transcriptional activator of the HO endonuclease gene, whereas ACE2 is not. In contrast, ACE2 is a transcriptional activator of the CTS1 gene (which encodes chitinase), whereas SWI5 is not. An additional parallel between the SWI5/HO pathway and the ACE2/CTS1 pathway is that HO and CTS1 both are cell cycle regulated in the same way, and HO and CTS1 both require the SWI4 and SWI6 transcriptional activators. Overproduction of either SWI5 or ACE2 permits transcriptional activation of the target gene from the other pathway, suggesting that the DNA-binding proteins are capable of binding in vivo to promoters that they do not usually activate. Chimeric SWI5/ACE2 protein fusion experiments suggest that promoter specificity resides in a domain distinct from the zinc finger domain.
A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.
Preferential paternal X-inactivation in the extra-embryonic tissues of the female mouse embryo is correlated with imprinted expression of the paternal allele of the Xist gene in pre-implantation development. Here we examine 11 CpG sites in Xist to determine whether differential methylation might be the molecular basis for imprinting. We find that three sites in the promoter region are methylated in eggs but not in sperm and that this differential methylation is maintained to the blastocyst stage when the paternal X-inactivation occurs. This is the first example of a primary gametic methylation imprint governing differential expression of parental alleles in pre-implantation embryos.
Genetic linkage maps have been constructed for the rice and maize genomes on the basis of orthologous loci detected with a common set of cDNA clones. Conserved linkage groups could be identified, which together account for more than two-thirds of both genomes. In some instances, entire chromosomes or chromosome arms are nearly identical with respect to gene order and gene content. The results also reveal that most of the genes (> 72%) duplicated during ancient polyploidization are still present in the maize genome in duplicate copy. The comparative maps of rice and maize provide a basis for interpreting molecular, genetic, and breeding information between these two important species and establish a framework for ultimately connecting the genetics of all grass species.
The nucleotide sequences of five of the six centromeres of the yeast Kluyveromyces lactis were determined. Mutual comparison of these sequences led to the following consensus: a short highly conserved box (5′-ATCACGTGA-3′) flanked by an AT-rich (±90%) stretch of ± 160 by followed by another conserved box (5′-TNNTTTATGTTTCCGAAAATTAATAT-3′).
These three elements were named K1CDEI, K1CDEII, and K1CDEIII respectively, by analogy with the situation in Saccharomyces cerevisiae. In addition, a second 100 by AT-rich (±90%) element, named K1CDE0, was found ± 150 by upstream of K1CDEI. The sequences of both K1CDEI and K1CDEIII are highly conserved between K. lactis and S. cerevisiae; however, centromeres of K. lactis do not function in S. cerevisiae and vice versa. The most obvious differences between the centromeres of the two yeast species are the length of the AT-rich CDEII, which is 161–164 by in K. lactis versus 78–86 by in S. cerevisiae and the presence in K. lactis of K1CDEO, which is not found in S. cerevisiae.
Based on the tenets of parental investment theory, the authors postulate that there was greater pressure to inhibit potentially maladaptive emotional, social, and sexual responses on prehistoric women than men in some contexts, resulting in enhanced inhibitory abilities in women in some domains. They reviewed studies whose researchers examined gender differences on social, behavioral, and cognitive tasks involving inhibition and found gender differences favoring female humans most consistent for social tasks (e.g., control of emotions), somewhat less pronounced for behavioral tasks (e.g., delay of gratification), and weak and inconsistent for cognitive tasks (e.g., conceptual tempo). This pattern was interrupted as being consistent with the position that gender differences in inhibition are relatively domain specific in nature, with women demonstrating greater abilities on tasks related to reproduction and childrearing, which is consistent with parental investment theory.
The genome of the yeast Saccharomyces cerevisiae has been completely sequenced through a worldwide collaboration. The sequence of 12,068 kilobases defines 5885 potential
protein-encoding genes, approximately 140 genes specifying ribosomal RNA, 40 genes for small nuclear RNA molecules, and 275
transfer RNA genes. In addition, the complete sequence provides information about the higher order organization of yeast's
16 chromosomes and allows some insight into their evolutionary history. The genome shows a considerable amount of apparent
genetic redundancy, and one of the major problems to be tackled during the next stage of the yeast genome project is to elucidate
the biological functions of all of these genes.
The primary structure of the small ribosomal subunit RNA (srRNA) molecule of the type strains of the ascosporogenous yeasts Debaryomyces hansenii, Pichia anomala (synonym: Hansenula anomala), Pichia membranaefaciens, Schizosaccharomyces pombe, Zygosaccharomyces rouxii and Dekkera bruxellensis was determined. The srRNA sequences were aligned with previously published sequences from fungi, including those of 5 Candida species, and an evolutionary tree was inferred.
The srRNA results were compared with chemotaxonomic criteria, e. g. the coenzyme Q system. The heterogeneity of the genera Candida and Pichia is clearly reflected by the srRNA analysis.
The first paperback edition of the book published in hardback in 1987 examines the consequences of the dramatic radiation of the angiosperms that took place towards the end of the Early Cretaceous upon plant communities, exploring such questions as how the early angiosperms were pollinated, and their impact on the diversity of terrestrial herbivores (both dinosaurs and mammals). Following an introductory chapter, the 9 other contributions (each abstracted seaparately) examine: a cladistic approach to the origin of the angiosperms; global palaeogeography and palaeoclimate of the Late Cretaceous and Early Tertiary; Mid-Cretaceous to Early Tertiary vegetation and climate - evidence from fossil leaves and wood, vegetational consequences of angiosperm diversification; time of appearance of floral features; evolution of insect pollination; interactions of angiosperms and herbivorous tetrapods; dinosaurs and land plants; and vegetational and mammalian faunal changes in the Early Tertiary of S England. -P.J.Jarvis
In this review we describe the various types of chromosomal abnormalities found in the distal short arm of the human X chromosome
and the most common clinical features associated with each type, emphasizing the underlying molecular mechanisms. The study
of these patients has significant implications for identifying the disease genes involved.
The transcription of the majority of the ribosomal protein (rp) genes of Saccharmoyces cerevisiae is activated by cis-acting elements, designated RPG boxes, which specifically bind the multifunctional protein RAPI in vitro.
To investigate to what extent this global system of tanscription regulation has been conserved, we have isolated a number of rp genes of the related yeast species Kluyveromyces lactis and Kluyveromyces marxianus, whose counterparts in Saccharomyces are controlled by RAPI. The coding regions of these genes showed a sequence similarity of about 90% when compared to their Saccharomyces counterparts. In contrast, little or no sequence similarity was found between the upstream regions and the intervening sequences of Kluyveromyces and Saccharomyces homologs. However, the occurrence and the position of the introns is conserved. The sequence data also show that the physical linkage that exists in S. cerevisiae between the rp genes encoding RP59 (CRY1), S24 and L46 is conserved in Kluyveromyces. Northern analysis demonstrated that each of the isolated Kluyveromyces genes is transcriptionally active.
By sequence comparison we idetified a number of conseerved sequences in the upstream region of each of the Kluyveromyces rp genes, which we designated the X, Z and RPGK boxes. The last one is highly similar, though not identical, to the S. cerevisiae RPG box.
Functional analysis of the intergenic region between the genes encoding Kluyveromyces ribosomal proteins S24 and L46 showed that the RPGK box (+Z box) functions as a transcriptional activator, while the X box acts as a trascriptional repressor. Band-shift assays confirmed the existence of a RAP1-like protein in Kluyveromyces that binds to the RPGK box but not to the S. cerevisiae RPG box. In contrast, S. cerevisiae RAP1 did recognize the RPGK box.
The present report summarizes molecular studies of parental origin and sex chromosome mosaicism in forty-one 45,X conceptuses, consisting of 29 spontaneous abortions and 12 liveborn individuals with Turner syndrome. Our studies indicate that most 45,X conceptuses have a single, maternally derived X chromosome, regardless of whether the conceptus is liveborn or spontaneously aborted. In studies of mosaicism, our identification of X- and Y-chromosome mosaics among 45,X spontaneous abortions indicates that mosaicism does not ensure survival to term of 45,X fetuses. However, the incidence of sex chromosome mosaicism is substantially higher in liveborn than in aborted 45,X conceptuses, indicating that the presence of a second cell line increases the likelihood of survival to term.
The results of a cytogenetic and molecular reinvestigation of a series of 52 patients with Turner's syndrome are reported. No evidence of Y chromosome material was found among the patients with a 45,X constitution but two patients were found to have a cell line with a r(Y) chromosome which was previously thought to be a r(X). The parental origin of the single X in the 45,X patients was maternal in 69% and paternal in 31%, a similar ratio to that seen among spontaneously aborted 45,X conceptuses. This suggests that X-chromosome imprinting is not responsible for the two grossly different phenotypes associated with a 45,X chromosome constitution. Approximately half of the structurally abnormal X chromosomes were maternal in origin and half paternal. This observation is consistent with either a meiotic or post-zygotic mitotic origin and at variance with the predominantly paternal origin reported for autosome structural abnormalities.
The TRP1 gene of the yeast Kluyveromyces lactis has been cloned from a genomic library by complementation of the Saccharomyces cerevisiae trp1-289 mutation. The gene was located within the clone by transposon mutagenesis and the coding region identified by DNA sequencing. This has indicated that K. lactis TRP1 encodes a 210-amino acid polypeptide which shows 53% identity to the homologous S. cerevisiae protein. The K. lactis TRP1 gene has been disrupted by substituting the S. cerevisiae URA3 gene for a large part of the TRP1 coding sequence. Replacement of the chromosomal TRP1 locus with this construction has enabled the production of non-reverting trp1- strains of K. lactis, while a genetic analysis of the disrupted allele confirmed that the TRP1 gene had been cloned. DNA sequencing has also shown that the K. lactis TRP1 sequence is flanked by genes encoding inorganic pyrophosphatase and histone H3, which we have designated IPP and HHT1 respectively. Hybridization studies have shown that in common with S. cerevisiae, K. lactis has two copies of the histone H3 gene. Each H3 gene is closely linked to a gene encoding histone H4 and in both yeast species the IPP gene is tightly linked to one of the histone gene pairs.
The core histone genes of Saccharomyces cerevisiae are arranged as duplicate nonallelic sets of specifically paired genes. The identity of structural organization between the duplicated gene pairs would have its simplest evolutionary origin in the duplication of a complete locus in a single event. In such a case, the time since the duplication of one of the genes should be identical to that since duplication of the gene adjacent to it on the chromosome. A calculation of the evolutionary distances between the coding DNA sequences of the histone genes leads to a duplication paradox: The extents of sequence divergence in the silent component of third-base positions for adjacent pairs of genes are not identical. Estimates of the evolutionary distance between the two H3-H4 noncoding intergene DNA sequences are large; the divergence between the two separate sequences is indistinguishable from the divergence between either of the regions and a randomly generated permutation of itself. These results suggest that the duplication event may have occurred much earlier than previously estimated. The potential age of the duplication, and the attractive simplicity of the duplication of both the H3-H4 and the H2A-H2B gene pairs having taken place in a single event, leads to the hypothesis that modern haploid S. cerevisiae may have evolved by diploidization or fusion of two ancient fungi.
Individuals with sex chromosomal anomalies are known to be at increased risk for learning problems and in some cases social or behavioral problems. Girls with an absent or structurally abnormal second sex chromosome (the Turner syndrome) have been found to have cognitive problem solving deficits and immature, inadequate social relationships. The present study attempted to link cognitive and social problems by assessing the girls' ability to process affective cues. 17 girls with karyotypes consistent with a diagnosis of Turner syndrome were compared to a group of 16 short-stature girls of comparable age, verbal intelligence scores, height, and family socioeconomic status on the Affective Discrimination Task, which required interpretation of affective intention from facial expression. The results revealed that the Turner syndrome girls were less accurate at inferring facial affect than the short-stature controls. Analyses revealed that the Turner syndrome girls performed more poorly on spatial, attentional, and short-term memory cognitive tasks and had more psychosocial problems than the short-stature controls. Ability to discriminate facial affect may be another area of cognitive weakness for girls with the Turner syndrome and may underlie the psychosocial problems found in this sample.
Numerous studies have demonstrated a significant depression in performance IQ (PIQ) in Turner Syndrome (TS) females, but the neuropsychological interpretation of this finding remains unclear. The present study addressed the following questions regarding the neuropsychological phenotype in TS: Are TS women neuropsychologically impaired? Is the impairment lateralized and How consistent is the neuropsychological phenotype across TS individuals? Unlike previous studies, the present study utilized both normal and brain damaged female controls. All subjects were given an extended Halstead-Reitan neuropsychological battery. The TS females were significantly worse than normals but not significantly different from brain damaged females in their overall level of neuropsychological functioning. However, their impairment was not lateralized. Their pattern of lateralizing findings was similar to that found in the Diffuse and Normal groups, but significantly different from either the right or left unilateral lesion groups. Fairly consistent deficits were found on tests of visuospatial skills and long term memory, but there was considerable variability in all the other test findings among TS individuals. The results are discussed in relation to the recent findings (Inglis and Lawson, 1981) that verbal-performance IQ discrepancies may be unreliable indicators of lateralized cerebral dysfunction in females. Hence the depressed PIQ in TS appears not to indicate predominantly right hemisphere dysfunction and may not even indicate a consistent underlying neuropsychological phenotype.
A method based on mutation distances as estimated from cytochrome c sequences is of general applicability.
Three experiments were conducted with the Tower of Hanoi task to assess problem solving ability in 6-, 7-, 8-, and 10-year-old nonretarded children and mentally retarded young adults of varying maturational ages. In Experiment 1 we gradually reduced the number of moves required for solution until subjects could solve the 3-disk tower-ending problem. Although all groups experienced difficulty with the standard 7-move problem, all but the trainable retarded group readily solved the 6-move problem. The trainable group did not reach a comparable level of success until the 4-move problem. On the 7-move problem the retarded groups performed at the level of nonretarded groups that were maturationally to 3 years younger. An analysis of first moves indicated that subject groups differed in the strategies they used to solve the problems. In Experiment 2, practice effects were ruled out as a source of the superior performance on the 6- than on the 7-move problem. In Experiment 3, 7- and 10-year-old nonretarded children and mentally retarded young adults did not differ on 5-move problems in which configuration of the goal states was varied. A comparison of all 5-move problems judged to have the same depth of search requirements indicated that the tower-ending problems were significantly easier to solve than the partial-tower-ending problems, which in turn were easier than the flat-ending problems. A limited depth of search capacity sets boundaries on the use of sophisticated strategies and, to a large extent, accounts for the retarded groups' maturational lag.
Although both Ras1 and Ras2 activate adenylyl cyclase in yeast, a number of differences can be observed regarding their function in the cAMP pathway. To explore the relative contribution of conserved and variable domains in determining these differences, chimeric RAS1-RAS2 or RAS2-RAS1 genes were constructed by swapping the sequences encoding the variable C-terminal domains. These constructs were expressed in a cdc25ts ras1 ras2 strain. Biochemical data show that the difference in efficacy of adenylyl cyclase activation between the two Ras proteins resides in the highly conserved N-terminal domain. This finding is supported by the observation that Ras2 delta, in which the C-terminal domain of Ras2 has been deleted, is a more potent activator of the yeast adenylyl cyclase than Ras1 delta, in which the C-terminal domain of Ras1 has been deleted. These observations suggest that amino acid residues other than the highly conserved residues of the effector domain within the N terminus may determine the efficiency of functional interaction with adenylyl cyclase. Similar levels of intracellular cAMP were found in Ras1, Ras1-Ras2, Ras1 delta, Ras2, and Ras2-Ras1 strains throughout the growth curve. This was found to result from the higher expression of Ras1 and Ras1-Ras2, which compensate for their lower efficacy in activating adenylyl cyclase. These results suggest that the difference between the Ras1 and the Ras2 phenotype is not due to their different efficacy in activating the cAMP pathway and that the divergent C-terminal domains are responsible for these differences, through interaction with other regulatory elements.
Embryonic development in mammals is distinct from that in other vertebrates because it depends on a small number of imprinted
genes that are specifically expressed from either the maternal or paternal genome. Why mammals are uniquely dependent on sexual
reproduction and how this dependency is dictated at a molecular level are questions that have been intensively investigated
during the past 2 years. Gene inactivation experiments have confirmed predictions that imprinted genes regulate embryonic
and placental growth and that DNA methylation is part of the imprinting mechanism. Despite these considerable achievements,
the reason why imprinted hemizygosity is used as a mechanism to regulate the intrauterine growth of mammalian embryos remains
elusive.
This paper presents results from a study of task performance on a variety of spatial tasks in 9-11 year-old children with Turner's Syndrome (T.S.), divided into those with genotype 45XO and those with Mixed genotypes, including isochromosomes of X and mosaicism. There was a significant overall effect of group reflecting impaired spatial cognition in T.S. with greater decrement in the 45XO group. Further investigation of the significant group by task interaction indicated that the group effects appeared on a visuo-perceptual task and on three visuo-constructional tasks but that there were no specific deficits in the T.S. groups on visuo-spatial or tactile-spatial tasks. In T.S., visuo-perceptual and visuo-constructive sub-systems of spatial skill may be more vulnerable than other components of spatial cognition, to the neuro-biological influences which contribute to the disorder. Such dissociation supports theories of modularity in the development of spatial skill. The spatial tasks which create difficulty overlap only partially with those for which there are sex differences amongst normal children and do not represent a simple exaggeration of normal male-female differences.
Genes that escape X inactivation have been recently found in human and in mouse. Although many of these genes have homologues on the Y chromosome that may compensate for expression from both X alleles in females, some have no Y homologues, and this presumably results in dosage differences between the sexes. Comparisons between human and mouse have revealed that the X-inactivation status of some genes differs significantly between the two species, suggesting continuous evolutionary changes in the sex chromosomes. Questions about the mechanisms of 'escape' are relevant to the understanding of gene regulation by X inactivation.
Saccharomyces cerevisiae RAP1 (Sc RAP1) is an essential protein which interacts with diverse genetic loci within the cell. RAP1 binds site-specifically to the consensus sequence, 5'-AYCYRTRCAYYW (UASRPG, where R = A or G, W = A or T, Y = C or T). In Kluyveromyces lactis (Kl) ribosomal protein-encoding genes (rp) retain functional RAP1-binding elements, suggesting the presence of a RAP1-like factor. Kl extracts display an activity capable of specifically binding to rp fragments bearing UASRPG. We subsequently isolated the Kl RAP1-encoding gene by homology to a subfragment which encodes the N terminus of the DNA-binding domain of Sc RAP1. The predicted amino acid (aa) sequence of Kl RAP1 indicates it is smaller than Sc RAP1 (666 vs. 827 aa) with the N terminus being truncated. The DNA-binding domain is virtually identical between the two RAP1 proteins, while the RIF1 domain is moderately conserved. The region between these two domains and the N-termini are highly divergent. Two potential UASRPG were identified in the 5' flanking region, suggesting an autoregulatory role for RAP1. Despite the similarities between the two proteins, KI RAP1 is unable to complement Sc rap1ts mutants, suggesting that domains essential for function in Sc are absent from the Kl protein.
A widely cited model of the evolution of functionally novel proteins (here called the model of mutation during non-functionality (MDN model)) holds that, after gene duplication, one gene copy is redundant and free to accumulate substitutions at random. By chance, some of these substitutions may suit the protein encoded by such a non-functional gene to a new function, which it can subsequently assume. Several lines of evidence contradict this hypothesis: (i) comparison of expressed duplicate genes from the tetraploid frog Xenopus laevis suggests that such genes are subject to purifying selection and are thus not free to accumulate substitutions at random; (ii) in a number of multi-gene families, there is now evidence that functionally distinct proteins have arisen not as a result of chance fixation of neutral variants but rather as a result of positive Darwinian selection; and (iii) the phenomenon of gene sharing, in which a single gene encodes a protein having two distinct functions, shows that gene duplication is not a necessary prerequisite to the evolution of a new protein function. A model for the evolution of new protein is proposed under which a period of gene sharing ordinarily precedes the evolution of functionally distinct proteins. Gene duplication then allows each daughter gene to specialize for one of the functions of the ancestral gene.(ABSTRACT TRUNCATED AT 250 WORDS)
The yeast Saccharomyces cerevisiae contains two clusters of eight genes each on chromosome 10 and 5, denoted, respectively, the COR and ARC regions. The genes in the COR region include TRS1 (a tRNA(Ser) gene), ANB1, CYC1, UTR1, UTR3, OSM1, tRNA(Gly) and RAD7 whereas the genes in the ARC region include TRS2 (a tRNA(Ser) gene), TIF51A, UTR5, ANP1, RAD23, UTR4, CYC7 and UTR2. We have performed a physical analysis of the ARC region, including determining DNA sequence of the 7529 nucleotides; the open reading frames; the size and orientation of the transcripts; and the phenotypes resulting from deletions or gene disruptions. The ARC region was systematically compared to the COR region which was previously described. The gene pairs CYC1-CYC7 and ANB1-TIF51A were previously shown to be, respectively, approximately 80% and 90% identical. tRNA(Ser) genes, TRS1 and TRS2, are located in both clusters 953 nt and 344 nt downstream of ANB1 and TIF51A, respectively. Some of the other gene pairs of these clusters are related in function and share only short segments of similarity distributed within the regions. The best alignment based on amino acid and nucleotide sequences indicates that the ARC and COR regions are ancestrally related by a duplication, a transposition, and a single rearrangement, followed by extensive divergence. These comparisons allowed an evaluation of distantly related sequences not obviously revealed by standard computer analysis. Surprisingly, the alignment suggested that a translated region of the ARC ANP1 gene and the COR tRNA(Gly) gene are ancestrally related. Also translated regions of the COR gene RAD7 share similarities with both of the two adjacent ARC genes, ANP1 and RAD23. Five examples of simple repeated amino acid and DNA sequences occurred in the ARC region but none in the COR region. We suggest that these repeated sequences played a role in the divergence of ARC genes.
Uniparental disomy (UPD) in humans is caused primarily by meiotic nondisjunction events, followed by trisomy or monosomy 'rescue'. The majority of cases appear to be associated with advanced maternal age, and may be initially detected as mosaic trisomies during routine prenatal diagnosis by chorionic villus sampling or amniocentesis. In addition, structural abnormalities including Robertsonian translocations, reciprocal translocations and supernumerary marker chromosomes appear to be associated with an increased risk of UPD. Predicting the phenotypic effects of UPD is complex, as three independent factors are involved: (i) effects of trisomy on the placenta or the fetus; (ii) autosomal recessive disease due to reduction to homozygosity; and (iii) imprinted gene effects for some chromosomes. To date, UPD in humans has been reported for 25 of the 47 possible uniparental types. Imprinting effects have been established with certainty for four human chromosomes that have homology to mouse chromosomes which have been shown to have significant phenotypic effects in uniparental animals. A normal phenotype has been reported for 14 other UPD types. Thus, collection of data on UPD cases in humans is providing an imprinting map analogous to the experimentally derived imprinting map in mouse. This human imprinting map has important clinical implications, particularly in the area of prenatal diagnosis.
To test the centromere misdivision model of isochromosome formation, we have defined the breakpoints of cytogenetically monocentric and dicentric Xq isochromosomes (i(Xq)) from Turner syndrome probands, using FISH with cosmids and YACs derived from a contig spanning proximal Xp. Seven different pericentromeric breakpoints were identified, with 10 of 11 of the i(Xq)s containing varying amounts of material from Xp. Only one of the eight cytogenetically monocentric i(Xq)s demonstrated a single alpha-satellite (DXZ1) signal, consistent with classical models involving centromere misdivision. The remaining seven were inconsistent with such a model and had breakpoints that spanned proximal Xp11.21: one was between DXZ1 and the most proximal marker, ZXDA; one occurred between the duplicated genes, ZXDA and ZXDB; two were approximately 2 Mb from DXZ1; two were adjacent to ALAS2 located 3.5 Mb from DXZ1; and the largest had a breakpoint just distal to DXS1013E, indicating the inclusion of 8 Mb of Xp DNA between centromeres. The three cytologically dicentric i(Xq)s had breakpoints distal to DXS423E in Xp11.22 and therefore contained > or = 12 Mb of DNA between centromeres. These data demonstrate that the majority of breakpoints resulting in i(Xq) formation are in band Xp11.2 and not in the centromere itself. Therefore, we hypothesize that the predominant mechanism of i(Xq) formation involves sequences in the proximal short arm that are prone to breakage and reunion events between sister chromatids or homologous X chromosomes.
Certain cell types give rise to progeny that adopt different patterns of gene expression in the absence of any differences in their environment. Cells of budding yeast give birth to mother and daughter cells that differ in that only mother cells express the HO endonuclease gene and thereby switch mating types. We describe the identification of five genes, called SHE1-SHE5, that encode cytoplasmic proteins required for mother-specific HO expression. She1p, which is identical to the minimyosin Myo4p, and She3p are not, however, mother-specific proteins. On the contrary, they accumulate in growing buds. She proteins might be required for the transport of factors that promote HO repression from the mother cell into its bud. In an accompanying paper, we show that SHE genes are needed for the accumulation in daughter nuclei of Ash1p, a repressor of HO.
Autism constitutes one of the best validated child psychiatric disorders. Empirical research has succeeded in delineating the key clinical phenomena, in demonstrating strong genetic influences on the underlying liability, and in identifying basic cognitive deficits. A range of neurobiological abnormalities has also been found, although the replicability of specific findings has not been high. An understanding of the causal processes leading to autism, and accounting for the marked variability in its manifestations, requires an integration across these different levels of enquiry. Although this is not yet possible, a partial integration provides a useful strategy for identifying key research questions, the limitations of existing hypotheses, and future research directions that are likely to prove fruitful. The research findings for each research level are critically reviewed in order to consider how to move towards an integration across levels.
In this paper, we consider the domain of executive functions (EFs) and their possible role in developmental psychopathologies. We first consider general theoretical and measurement issues involved in studying EFs and then review studies of EFs in four developmental psychopathologies: attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), autism, and Tourette syndrome (TS).
Our review reveals that EF deficits are consistently found in both ADHD and autism but not in CD (without ADHD) or in TS. Moreover, both the severity and profile of EF deficits appears to differ across ADHD and autism. Molar EF deficits are more severe in the latter than the former. In the few studies of more specific EF tasks, there are impairments in motor inhibition in ADHD but not in autism, whereas there are impairments in verbal working memory in autism but not ADHD. We close with a discussion of implications for future research.
Genomic comparison of two sibling yeast species, Saccharomyces bayanus and Saccharomyces cerevisiae, was performed by Southern blot analysis with various S. cerevisiae gene probes following electrophoretic karyotyping. Fifteen genes on chromosome IV of S. cerevisiae were examined and classified into two groups. Gene probes of CEN4 and TRP1, as well as six other genes located on the left arm of the chromosome hybridized to a 1100-kb chromosome of S. bayanus that is smaller than chromosome IV of S. cerevisiae. On the other hand, probes of seven genes located on the right arm of chromosome IV hybridized to a 1350-kb chromosome that is homeologous to chromosome IV, judging from its size. Two genes located on the left arm of chromosome II hybridized to the 1350-kb chromosome, while four genes on the right arm hybridized to the 1100-kb chromosome. These pieces of evidence indicate that chromosomes II and IV of S. cerevisiae are rearranged into 1350-kb and 1100-kb chromosomes in S. bayanus. Furthermore, it is suggested that chromosome XV is rearranged into two chromosomes (800 and 850 kb in size) in S. bayanus. The translocation points of chromosomes II and IV were delimited using S. cerevisiae prime clone membranes. The results indicated that the translocation points are located close to the FUR4 locus on chromosome II and close to the RAD57 locus on chromosome IV.
The Saccharomyces cerevisiae gene TOR2 encodes a putative phosphatidylinositol kinase that has two essential functions. One function is redundant with TOR1, a TOR2 homolog, and is required for signaling translation initiation and early G1 progression. The second essential function is unique to TOR2. Here we report that loss of the TOR2-unique function disrupts polarized distribution of the actin cytoskeleton. A screen for dosage suppressors of a dominant negative TOR2 allele identified TCP20/CCT6, encoding a subunit of the cytosolic chaperonin TCP-1 that is involved in the biogenesis of actin structures. Overexpression of TCP20 restores growth and polarized distribution of the actin cytoskeleton in a tor2 mutant. TCP20 overexpression does not restore growth in a tor1 tor2 double mutant. We suggest that the unique function of the phosphatidylinositol kinase homolog TOR2 is required for signaling organization of the actin cytoskeleton during the cell cycle. TOR2, via its two functions, may thus integrate temporal and spatial control of cell growth.