Identifying concerted evolution and gene conversion in mammalian gene pairs lasting over 100 million years

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
BMC Evolutionary Biology (Impact Factor: 3.37). 02/2009; 9(1):156. DOI: 10.1186/1471-2148-9-156
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ABSTRACT Concerted evolution occurs in multigene families and is characterized by stretches of homogeneity and higher sequence similarity between paralogues than between orthologues. Here we identify human gene pairs that have undergone concerted evolution, caused by ongoing gene conversion, since at least the human-mouse divergence. Our strategy involved the identification of duplicated genes with greater similarity within a species than between species. These genes were required to be present in multiple mammalian genomes, suggesting duplication early in mammalian divergence. To eliminate genes that have been conserved due to strong purifying selection, our analysis also required at least one intron to have retained high sequence similarity between paralogues.
We identified three human gene pairs undergoing concerted evolution (BMP8A/B, DDX19A/B, and TUBG1/2). Phylogenetic investigations reveal that in each case the duplication appears to have occurred prior to eutherian mammalian radiation, with exactly two paralogues present in all examined species. This indicates that all three gene duplication events were established over 100 million years ago.
The extended duration of concerted evolution in multiple distant lineages suggests that there has been prolonged homogenization of specific segments within these gene pairs. Although we speculate that selection for homogenization could have been utilized in order to maintain crucial homo- or hetero- binding domains, it remains unclear why gene conversion has persisted for such extended periods of time. Through these analyses, our results demonstrate additional examples of a process that plays a definite, although unspecified, role in molecular evolution.

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Available from: Andrew R Carson, Sep 27, 2015
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    • "However, genome-wide comparison of rates and asymmetries of sequence evolution between paralogs and singletons is difficult owing to the lack of a properly matched control: conserved gene families are also more likely to retain duplications [30,31], (but compare to Ref. [32]), thus creating an apparent decrease in evolution rate in paralogs than in singletons in a genome-wide comparison [33]. One approach to eliminate this confounding is to compare paralogs to their pre-duplication sister singleton orthologs [9,10,13,26], which requires sequence data analysed on a detailed phylogenetic context encompassing a number of closely related genomes, and thus was, until recently, limited to unicellular organisms. Here we report the analysis of rates and asymmetries of sequence and expression evolution in paralogous genes present in twelve Drosophila genomes [34] juxtaposed to those in their nearest singleton outgroup, a strategy recently employed for the analysis of duplicated genes in pairs of species of yeast [26], Drosophila[10] and rodents [9], but, to the best of our knowledge, has not been used on data encompassing entire phylogenies. "
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    ABSTRACT: Duplicated genes can indefinately persist in genomes if either both copies retain the original function due to dosage benefit (gene conservation), or one of the copies assumes a novel function (neofunctionalization), or both copies become required to perform the function previously accomplished by a single copy (subfunctionalization), or through a combination of these mechanisms. Different models of duplication retention imply different predictions about substitution rates in the coding portion of paralogs and about asymmetry of these rates. We analyse sequence evolution asymmetry in paralogs present in 12 Drosophila genomes using the nearest non-duplicated orthologous outgroup as a reference. Those paralogs present in D. melanogaster are analysed in conjunction with the asymmetry of expression rate and ubiquity and of segregating non-synonymous polymorphisms in the same paralogs. Paralogs accumulate substitutions, on average, faster than their nearest singleton orthologs. The distribution of paralogs' substitution rate asymmetry is overdispersed relative to that of orthologous clades, containing disproportionally more unusually symmetric and unusually asymmetric clades. We show that paralogs are more asymmetric in: a) clades orthologous to highly constrained singleton genes; b) genes with high expression level; c) genes with ubiquitous expression and d) non-tandem duplications. We further demonstrate that, in each asymmetrically evolving pair of paralogs, the faster evolving member of the pair tends to have lower average expression rate, lower expression uniformity and higher frequency of non-synonymous SNPs than its slower evolving counterpart. Our findings are consistent with the hypothesis that many duplications in Drosophila are retained despite stabilising selection being more relaxed in one of the paralogs than in the other, suggesting a widespread unfinished pseudogenization. This phenomenon is likely to make detection of neo- and subfunctionalization signatures difficult, as these models of duplication retention also predict asymmetries in substitution rates and expression profiles.Reviewers: This article has been reviewed by Dr. Jia Zeng (nominated by Dr. I. King Jordan), Dr. Fyodor Kondrashov and Dr. Yuri Wolf.
    Biology Direct 01/2014; 9(1):2. DOI:10.1186/1745-6150-9-2 · 4.66 Impact Factor
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    • "To rule out the possibility that the isoelectric point of exogenous γ-tubulin 2 expressed in P19 cells substantially differs from that in mouse tissues, we compared the expression of γ-tubulins in mouse brain and mouse liver, where Tubg2 expression is high and low, respectively [23], [24]. For this, we used immunoblotting after 2D-PAGE separation of samples containing similar total protein amounts. "
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    ABSTRACT: γ-Tubulin is the key protein for microtubule nucleation. Duplication of the γ-tubulin gene occurred several times during evolution, and in mammals γ-tubulin genes encode proteins which share ∼97% sequence identity. Previous analysis of Tubg1 and Tubg2 knock-out mice has suggested that γ-tubulins are not functionally equivalent. Tubg1 knock-out mice died at the blastocyst stage, whereas Tubg2 knock-out mice developed normally and were fertile. It was proposed that γ-tubulin 1 represents ubiquitous γ-tubulin, while γ-tubulin 2 may have some specific functions and cannot substitute for γ-tubulin 1 deficiency in blastocysts. The molecular basis of the suggested functional difference between γ-tubulins remains unknown. Here we show that exogenous γ-tubulin 2 is targeted to centrosomes and interacts with γ-tubulin complex proteins 2 and 4. Depletion of γ-tubulin 1 by RNAi in U2OS cells causes impaired microtubule nucleation and metaphase arrest. Wild-type phenotype in γ-tubulin 1-depleted cells is restored by expression of exogenous mouse or human γ-tubulin 2. Further, we show at both mRNA and protein levels using RT-qPCR and 2D-PAGE, respectively, that in contrast to Tubg1, the Tubg2 expression is dramatically reduced in mouse blastocysts. This indicates that γ-tubulin 2 cannot rescue γ-tubulin 1 deficiency in knock-out blastocysts, owing to its very low amount. The combined data suggest that γ-tubulin 2 is able to nucleate microtubules and substitute for γ-tubulin 1. We propose that mammalian γ-tubulins are functionally redundant with respect to the nucleation activity.
    PLoS ONE 01/2012; 7(1-7). DOI:10.1371/journal.pone.0029919 · 3.23 Impact Factor
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    • "[45] and ENSEMBL databases ( [46]. Identified proteins were then located on genomes for syntenic analyses of the most recent genome sequence assemblies: pig (Sus scrofa: ENSEMBL Sscrofa9), cow (Bos Taurus: NCBI Btau5.2), "
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    ABSTRACT: SAL1 (salivary lipocalin) is a member of the OBP (Odorant Binding Protein) family and is involved in chemical sexual communication in pig. SAL1 and its relatives may be involved in pheromone and olfactory receptor binding and in pre-mating behaviour. The evolutionary history and the selective pressures acting on SAL1 and its orthologous genes have not yet been exhaustively described. The aim of the present work was to study the evolution of these genes, to elucidate the role of selective pressures in their evolution and the consequences for their functions. Here, we present the evolutionary history of SAL1 gene and its orthologous genes in mammals. We found that (1) SAL1 and its related genes arose in eutherian mammals with lineage-specific duplications in rodents, horse and cow and are lost in human, mouse lemur, bushbaby and orangutan, (2) the evolution of duplicated genes of horse, rat, mouse and guinea pig is driven by concerted evolution with extensive gene conversion events in mouse and guinea pig and by positive selection mainly acting on paralogous genes in horse and guinea pig, (3) positive selection was detected for amino acids involved in pheromone binding and amino acids putatively involved in olfactory receptor binding, (4) positive selection was also found for lineage, indicating a species-specific strategy for amino acid selection. This work provides new insights into the evolutionary history of SAL1 and its orthologs. On one hand, some genes are subject to concerted evolution and to an increase in dosage, suggesting the need for homogeneity of sequence and function in certain species. On the other hand, positive selection plays a role in the diversification of the functions of the family and in lineage, suggesting adaptive evolution, with possible consequences for speciation and for the reinforcement of prezygotic barriers.
    BMC Evolutionary Biology 05/2011; 11(1):148. DOI:10.1186/1471-2148-11-148 · 3.37 Impact Factor
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