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... These measures range from 4 : 1 to 15 : 1 with conversion events much more likely than COs [119,120]. CO interference has been demonstrated to vary across different organisms [39,. Because of multiple levels of control, predicting responses of CO rates to both environmental and evolutionary forces (e.g. ...
For over a century, scientists have known that meiotic recombination rates can vary considerably among individuals, and that environmental conditions can modify recombination rates relative to the background. A variety of external and intrinsic factors such as temperature, age, sex and starvation can elicit ‘plastic’ responses in recombination rate. The influence of recombination rate plasticity on genetic diversity of the next generation has interesting and important implications for how populations evolve. Further, many questions remain regarding the mechanisms and molecular processes that contribute to recombination rate plasticity. Here, we review 100 years of experimental work on recombination rate plasticity conducted in Drosophila melanogaster. We categorize this work into four major classes of experimental designs, which we describe via classic studies in D. melanogaster. Based on these studies, we highlight molecular mechanisms that are supported by experimental results and relate these findings to studies in other systems. We synthesize lessons learned from this model system into experimental guidelines for using recent advances in genotyping technologies, to study recombination rate plasticity in non-model organisms. Specifically, we recommend (1) using fine-scale genome-wide markers, (2) collecting time-course data, (3) including crossover distribution measurements, and (4) using mixed effects models to analyse results. To illustrate this approach, we present an application adhering to these guidelines from empirical work we conducted in Drosophila pseudoobscura.
This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
Meiosis is a specialized type of cell division characterized by a single round of DNA replication and two rounds of chromosome segregation, ultimately resulting in four haploid cells. During meiosis I, chromosomes align and reciprocal recombination results in the formation of a crossover, creating the tension required to properly segregate homologs during the first round of meiosis.
Two mechanisms involved in regulating the occurrence of crossing over are assurance and interference. Crossover assurance describes the phenomenon that at least one crossover will form between each pair of homologous chromosomes during prophase I. Crossover interference, on the other hand, describes the nonrandom placement of crossovers between homologs, increasing the probability that a second crossover will occur at a discrete distance away from the first one.
In addition to assurance and interference, chromosome size may play a role in the rate of meiotic recombination during prophase I. As a result of crossover assurance, small chromosomes receive a minimum of one crossover, the obligate crossover. Assuming chromosome size does not influence the rate of recombination, pairs of large chromosomes should experience the same number of crossovers per base pair as small chromosomes. Previous studies have been inconsistent: Kaback et al. (1999) saw decreased rates of crossing over between large chromosomes relative to small ones, suggesting that crossover interference acts across a larger distance on large chromosomes. Turney et al. (2004), however, saw no such effect, suggesting that these findings may be site- or sequence-specific.
The current study used the Cre-loxP system to create translocated chromosomes, decreasing the size of chromosome VIII from 562 kb to 125 kb. The rate of crossing over was evaluated using nutrient marker genes that were inserted on the left arm of chromosome VIII to facilitate phenotypic detection of crossing over between homologous translocated chromosomes in comparison to crossing over between homologous nontranslocated chromosomes.
Translocated strains were attempted, though further testing suggests that the translocation itself may be lethal. In the future, we plan to further investigate the potential lethal nature of the translocation.
We also experienced difficulty in curing yeast cells of the Cre expression plasmid: as pSH47 was removed, translocated chromosomes reverted to nontranslocated chromosomes. In addition, crossing over in nontranslocated yeast, along with subsequent molecular analysis, revealed that one of the marker genes presumed to be on the left arm of chromosome VIII is, in fact, located on a different chromosome, preventing analysis of crossing over in this region. As a result, we were unable to proceed with current experimentation.
Meiosis is the specialized process of cell division utilized during gametogenesis in all sexually reproducing eukaryotes, which consists of one round of DNA replication followed by two rounds of chromosome segregation and results in four haploid cells. Crossovers between homologous chromosomes promote proper alignment and segregation of chromosomes during meiosis.
Crossover interference is a genetic phenomenon in which crossovers are non-randomly placed along chromosomes. Crossover assurance ensures that every homologous chromosome pair obtains at least one crossover during Prophase I. Crossovers physically connect homologous pairs, allowing spindle fibers to attach and separate homologs properly. However, some organisms have shown an ability to segregate chromosomes that fail to receive at least one crossover, a phenomenon termed distributive disjunction.
In Saccharomyces cerevisiae, mutation of either Tid1 or Ndj1 results in a similar defect in crossover interference. The overall number of crossovers is not substantially different from the wild type, however they are distributed more randomly with respect to each other. In this thesis, the roles of Tid1 and Ndj1 on crossover assurance and distributive disjunction have been further elucidated through use of knock-out mutants and tetrad dissection.
To analyze meiotic chromosome segregation in isogenic tid1 and ndj1 strains, the spore viability of dissected tetrads was utilized as an indirect measure of nondisjunction events. An elevated number of 2- and 0- spore viable tetrads were seen in ndj1, but not tid1 yeast, confirming previous results. Elevated 2- and 0- spore viable tetrads are an indication of meiosis I (MI) nondisjunction, commonly resulting from failure of crossover formation. These results suggest crossover assurance is disrupted in njd1, but not tid1 mutants. However, MI chromosome segregation is an indirect readout of crossover formation; distributive disjunction, for example, can lead to proper segregation of achiasmate chromosomes.
To determine if distributive disjunction is functional in yeast, wild type, tid1 and ndj1 versions of diploid yeast carrying a single homeologous pair of chromosomes were constructed. These strains have one chromosome (chr. III or V) replaced with one from a closely related species of yeast. The homeologous chromosome functionally replaces the homolog, however crossovers are significantly reduced between homeologs. A spore viability pattern typical of MI nondisjunction was detected in ndj1 mutants, but not in tid1 mutants. In the context of these homeologs, this pattern is suggestive of a role for Ndj1, but not Tid1, in distributive disjunction. Further, these results suggest that tid1 and ndj1 mutant yeast may not be different in their competence for crossover assurance.
To directly assay competence for crossover assurance in native mutants, the incidence of E0 chromosome pairs (those lacking crossovers) was determined. To do this we assayed crossover formation along the length of chromosome III of isogenic wild type, ndj1 and tid1 mutant strains. The incidence of E0 chromosomes was comparably elevated in both tid1 and ndj1 mutant yeast, suggesting that crossover assurance is nonfunctional in both strains.
We find evidence that supports the idea that interference and assurance are genetically linked. Our data also suggests that distributive disjunction may be genetically separable from some meiotic genes.
Recombination is fundamental to meiosis in many species and generates variation on which natural selection can act, yet fine-scale linkage maps are cumbersome to construct. We generated a fine-scale map of recombination rates across two major chromosomes in Drosophila persimilis using 181 SNP markers spanning two of five major chromosome arms. Using this map, we report significant fine-scale heterogeneity of local recombination rates. However, we also observed "recombinational neighborhoods," where adjacent intervals had similar recombination rates after excluding regions near the centromere and telomere. We further found significant positive associations of fine-scale recombination rate with repetitive element abundance and a 13-bp sequence motif known to associate with human recombination rates. We noted strong crossover interference extending 5-7 Mb from the initial crossover event. Further, we observed that fine-scale recombination rates in D. persimilis are strongly correlated with those obtained from a comparable study of its sister species, D. pseudoobscura. We documented a significant relationship between recombination rates and intron nucleotide sequence diversity within species, but no relationship between recombination rate and intron divergence between species. These results are consistent with selection models (hitchhiking and background selection) rather than mutagenic recombination models for explaining the relationship of recombination with nucleotide diversity within species. Finally, we found significant correlations between recombination rate and GC content, supporting both GC-biased gene conversion (BGC) models and selection-driven codon bias models. Overall, this genome-enabled map of fine-scale recombination rates allowed us to confirm findings of broader-scale studies and identify multiple novel features that merit further investigation.
The aim of genetical research is to determine the topography of the genetical material in various organisms and to represent the mutable genes on each chromosome as occupying positions on a linear map. The order and spacing of the genes in the main has to be inferred from the amounts of recombination exhibited by sets of genes when appropriately designed backcross experiments are carried out, though this process is, occasionally, aided by cytological studies and the artificial production of rearrangements. This chapter highlights the recent mathematical developments and the cytological evidence on which its main ideas are founded, and to give a survey, arranged partly in historical and partly in logical order, of the development of the theoretical concepts involved in the study of linkage. The focus is on the normal situations in diploids, as the theory of linkage in polysomic inheritance is relatively far less advanced. The whole subject of estimation of recombination values is omitted; all though it is of extreme practical importance it is not directly relevant.
The ease of obtaining synovial fluid and the recent well deserved emphasis on demonstration of monosodium urate (MSU) crystals in synovial fluid as a diagnostic aid in gout have focused most attention on the synovial fluid in this disease. Interaction of MSU crystals and polymorphonuclear leukocytes in synovial fluid is clearly important in pathogenesis of gouty synovitis. However, synovial membrane also has a role in gouty arthritis. This report reviews the synovial membrane findings and some of their implications. Structures possibly confused with MSU in electron microscopic studies are also discussed. The following aspects are dealt with: tophi; acute gouty synovitis; chronic gouty synovitis; and problems in ultrastructural identification of urate crystals. (29 references).
Visual disturbances in patients with breast carcinoma may result from choroidal metastases. Metastases were bilateral in 41% of patients and the choroid was the first site of metastasis in 25%. Therefore awareness of this 'rare' condition is essential for any doctor seeing patients with breast cancer; consultation with an ophthalmologist and radiotherapist is mandatory. Radiation therapy is the treatment of choice, producing an 80% response rate (complete resolution in 25%). The final catastrophe of blindness in these patients can be prevented.