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Genetics Dec 2018Meiotic recombination is a major driver of genome evolution by creating new genetic combinations. To probe the factors driving variability of meiotic recombination, we...
Meiotic recombination is a major driver of genome evolution by creating new genetic combinations. To probe the factors driving variability of meiotic recombination, we used a high-throughput method to measure recombination rates in hybrids between SK1 and a total of 26 strains from different geographic origins and habitats. Fourteen intervals were monitored for each strain, covering chromosomes VI and XI entirely, and part of chromosome I. We found an average number of crossovers per chromosome ranging between 1.0 and 9.5 across strains ("domesticated" or not), which is higher than the average between 0.5 and 1.5 found in most organisms. In the different intervals analyzed, recombination showed up to ninefold variation across strains but global recombination landscapes along chromosomes varied less. We also built an incomplete diallel experiment to measure recombination rates in one region of chromosome XI in 10 different crosses involving five parental strains. Our overall results indicate that recombination rate is increasingly positively correlated with sequence similarity between homologs (i) in DNA double-strand-break-rich regions within intervals, (ii) in entire intervals, and (iii) at the whole genome scale. Therefore, these correlations cannot be explained by effects only. We also estimated that and effects explained 38 and 17%, respectively, of the variance of recombination rate. In addition, by using a quantitative genetics analysis, we identified an inbreeding effect that reduces recombination rate in homozygous genotypes, while other interaction effects (specific combining ability) or additive effects (general combining ability) are found to be weak. Finally, we measured significant crossover interference in some strains, and interference intensity was positively correlated with crossover number.
Topics: Chromosomes, Fungal; Crossing Over, Genetic; DNA Breaks, Double-Stranded; Genome, Fungal; Genotype; Inbreeding; Meiosis; Recombination, Genetic; Saccharomyces cerevisiae
PubMed: 30291109
DOI: 10.1534/genetics.118.301644 -
Methods in Molecular Biology (Clifton,... 2009Traditional methods for surveying meiotic recombination in humans are limited to pedigree and linkage disequilibrium analyses. We have developed assays that allow the... (Review)
Review
Traditional methods for surveying meiotic recombination in humans are limited to pedigree and linkage disequilibrium analyses. We have developed assays that allow the direct detection of crossover and gene conversion molecules in batches of sperm DNA. To date, we have characterized 26 recombination hotspots by allele-specific PCR and selectively amplified recombinant DNA molecules from these regions. These analyses have revealed that meiotic crossover hotspots in humans are highly localized and flanked by DNA segments where recombination is suppressed. The centers of crossover hotspots are also active in noncrossover recombination, displaying short conversion tracts.
Topics: Algorithms; Cytogenetic Analysis; Humans; Male; Meiosis; Models, Biological; Polymerase Chain Reaction; Recombination, Genetic; Spermatozoa
PubMed: 19799191
DOI: 10.1007/978-1-59745-527-5_20 -
Genetics Jun 2017Meiotic homologous recombination, a critical event for ensuring faithful chromosome segregation and creating genetic diversity, is initiated by programmed DNA...
Meiotic homologous recombination, a critical event for ensuring faithful chromosome segregation and creating genetic diversity, is initiated by programmed DNA double-strand breaks (DSBs) formed at recombination hotspots. Meiotic DSB formation is likely to be influenced by other DNA-templated processes including transcription, but how DSB formation and transcription interact with each other has not been understood well. In this study, we used fission yeast to investigate a possible interplay of these two events. A group of hotspots in fission yeast are associated with sequences similar to the cyclic AMP response element and activated by the ATF/CREB family transcription factor dimer Atf1-Pcr1. We first focused on one of those hotspots, , and Atf1. Our results showed that multiple transcripts, shorter than the full-length messenger RNA, emanate from a region surrounding the hotspot. Interestingly, we found that the previously known recombination-activation region of Atf1 is also a transactivation domain, whose deletion affected DSB formation and short transcript production at These results point to a possibility that the two events may be related to each other at In fact, comparison of published maps of meiotic transcripts and hotspots suggested that hotspots are very often located close to meiotically transcribed regions. These observations therefore propose that meiotic DSB formation in fission yeast may be connected to transcription of surrounding regions.
Topics: Activating Transcription Factor 1; Activating Transcription Factors; Cyclic AMP Response Element-Binding Protein; DNA Breaks, Double-Stranded; Homologous Recombination; Meiosis; Phosphoproteins; Recombination, Genetic; Schizosaccharomyces; Schizosaccharomyces pombe Proteins
PubMed: 28396503
DOI: 10.1534/genetics.116.197954 -
PLoS Genetics Jun 2016In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations...
In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination. PRDM9 binds to DNA at hotspots through its zinc finger domain and activates recombination by trimethylating histone H3K4 on adjacent nucleosomes through its PR/SET domain. Recently, the isolated PR/SET domain of PRDM9 was shown capable of also trimethylating H3K36 in vitro, raising the question of whether this reaction occurs in vivo during meiosis, and if so, what its function might be. Here, we show that full-length PRDM9 does trimethylate H3K36 in vivo in mouse spermatocytes. Levels of H3K4me3 and H3K36me3 are highly correlated at hotspots, but mutually exclusive elsewhere. In vitro, we find that although PRDM9 trimethylates H3K36 much more slowly than it does H3K4, PRDM9 is capable of placing both marks on the same histone molecules. In accord with these results, we also show that PRDM9 can trimethylate both K4 and K36 on the same nucleosomes in vivo, but the ratio of K4me3/K36me3 is much higher for the pair of nucleosomes adjacent to the PRDM9 binding site compared to the next pair further away. Importantly, H3K4me3/H3K36me3-double-positive nucleosomes occur only in regions of recombination: hotspots and the pseudoautosomal (PAR) region of the sex chromosomes. These double-positive nucleosomes are dramatically reduced when PRDM9 is absent, showing that this signature is PRDM9-dependent at hotspots; the residual double-positive nucleosomes most likely come from the PRDM9-independent PAR. These results, together with the fact that PRDM9 is the only known mammalian histone methyltransferase with both H3K4 and H3K36 trimethylation activity, suggest that trimethylation of H3K36 plays an important role in the recombination process. Given the known requirement of H3K36me3 for double strand break repair by homologous recombination in somatic cells, we suggest that it may play the same role in meiosis.
Topics: Animals; Binding Sites; DNA Breaks, Double-Stranded; DNA Repair; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Histones; Homologous Recombination; Meiosis; Mice; Mice, Inbred C57BL; Nucleosomes; Recombination, Genetic; Zinc Fingers
PubMed: 27362481
DOI: 10.1371/journal.pgen.1006146 -
Genome Dynamics 2009In the last 30 years it has become evident that patterns of meiotic recombination can be highly variable among individuals. The evidence comes from both low and high... (Review)
Review
In the last 30 years it has become evident that patterns of meiotic recombination can be highly variable among individuals. The evidence comes from both low and high resolution analyses of hotspots of recombination in human and other species. In addition, a comparison of the recombination profiles in closely related species such as human and chimpanzee reveals essentially no correlation in the position of hotspots. Although the variation in hotspots of meiotic recombination is clearly documented, the mechanisms responsible for such variation are far from being understood. Here we will review the available evidence of natural variation in meiotic recombination and will discuss potential implications of this variation on the functional mechanisms of crossover formation and control.
Topics: Computational Biology; Genetic Variation; Humans; Meiosis; Recombination, Genetic
PubMed: 18948711
DOI: 10.1159/000166623 -
The New Phytologist Apr 2010Polyploidization and recombination are two important processes driving evolution through the building and reshaping of genomes. Allopolyploids arise from hybridization... (Review)
Review
Polyploidization and recombination are two important processes driving evolution through the building and reshaping of genomes. Allopolyploids arise from hybridization and chromosome doubling among distinct, yet related species. Polyploids may display novel variation relative to their progenitors, and the sources of this variation lie not only in the acquisition of extra gene dosages, but also in the genomic changes that occur after divergent genomes unite. Genomic changes (deletions, duplications, and translocations) have been detected in both recently formed natural polyploids and resynthesized polyploids. In resynthesized Brassica napus allopolyploids, there is evidence that many genetic changes are the consequence of homoeologous recombination. Homoeologous recombination can generate novel gene combinations and phenotypes, but may also destabilize the karyotype and lead to aberrant meiotic behavior and reduced fertility. Thus, natural selection plays a role in the establishment and maintenance of fertile natural allopolyploids that have stabilized chromosome inheritance and a few advantageous chromosomal rearrangements. We discuss the evidence for genome rearrangements that result from homoeologous recombination in resynthesized B. napus and how these observations may inform phenomena such as chromosome replacement, aneuploidy, non-reciprocal translocations and gene conversion seen in other polyploids.
Topics: Brassica napus; Chromosome Pairing; Chromosome Segregation; Models, Genetic; Polyploidy; Recombination, Genetic
PubMed: 20002315
DOI: 10.1111/j.1469-8137.2009.03089.x -
The New Phytologist Dec 2020Meiotic recombination rates vary considerably between species, populations and individuals. The genetic exchange between homologous chromosomes plays a major role in...
Meiotic recombination rates vary considerably between species, populations and individuals. The genetic exchange between homologous chromosomes plays a major role in evolution by breaking linkage between advantageous and deleterious alleles in the case of introgressions. Identifying recombination rate modifiers is thus of both fundamental and practical interest to understand and utilize variation in meiotic recombination rates. We investigated recombination rate variation in a large intraspecific hybrid population (named HEB-25) derived from a cross between domesticated barley and 25 wild barley accessions. We observed quantitative variation in total crossover number with a maximum of a 1.4-fold difference between subpopulations and increased recombination rates across pericentromeric regions. The meiosis-specific α-kleisin cohesin subunit REC8 was identified as a candidate gene influencing crossover number and patterning. Furthermore, we quantified wild barley introgression patterns and revealed how local and genome-wide recombination rate variation shapes patterns of introgression. The identification of allelic variation in REC8 in combination with the observed changes in crossover patterning suggest a difference in how chromatin loops are tethered to the chromosome axis, resulting in reduced crossover suppression across pericentromeric regions. Local and genome-wide recombination rate variation is shaping patterns of introgressions and thereby directly influences the consequences of linkage drag.
Topics: Genetic Linkage; Genome; Hordeum; Meiosis; Recombination, Genetic
PubMed: 32659029
DOI: 10.1111/nph.16810 -
Methods in Molecular Biology (Clifton,... 2009The fission yeast Schizosaccharomyces pombe is well-suited for studying meiotic recombination. Methods are described here for culturing S. pombe and for genetic assays... (Review)
Review
The fission yeast Schizosaccharomyces pombe is well-suited for studying meiotic recombination. Methods are described here for culturing S. pombe and for genetic assays ofintragenic recombination (gene conversion), intergenic recombination (crossing-over), and spore viability. Both random spore and tetrad analyses are described.
Topics: Cell Culture Techniques; Genetic Techniques; Meiosis; Models, Biological; Recombination, Genetic; Schizosaccharomyces; Spores, Fungal
PubMed: 19799177
DOI: 10.1007/978-1-59745-527-5_6 -
Heredity Mar 2017The proportion of an individual's genome that is identical by descent (GWIBD) can be estimated from pedigrees (inbreeding coefficient 'Pedigree F') or molecular markers...
The proportion of an individual's genome that is identical by descent (GWIBD) can be estimated from pedigrees (inbreeding coefficient 'Pedigree F') or molecular markers ('Marker F'), but both estimators come with error. Assuming unrelated pedigree founders, Pedigree F is the expected proportion of GWIBD given a specific inbreeding constellation. Meiotic recombination introduces variation around that expectation (Mendelian noise) and related pedigree founders systematically bias Pedigree F downward. Marker F is an estimate of the actual proportion of GWIBD but it suffers from the sampling error of markers plus the error that occurs when a marker is homozygous without reflecting common ancestry (identical by state). We here show via simulation of a zebra finch and a human linkage map that three aspects of meiotic recombination (independent assortment of chromosomes, number of crossovers and their distribution along chromosomes) contribute to variation in GWIBD and thus the precision of Pedigree and Marker F. In zebra finches, where the genome contains large blocks that are rarely broken up by recombination, the Mendelian noise was large (nearly twofold larger s.d. values compared with humans) and Pedigree F thus less precise than in humans, where crossovers are distributed more uniformly along chromosomes. Effects of meiotic recombination on Marker F were reversed, such that the same number of molecular markers yielded more precise estimates of GWIBD in zebra finches than in humans. As a consequence, in species inheriting large blocks that rarely recombine, even small numbers of microsatellite markers will often be more informative about inbreeding and fitness than large pedigrees.
Topics: Animals; Chromosome Mapping; Finches; Genetic Linkage; Genetic Markers; Genotyping Techniques; Homozygote; Humans; Inbreeding; Meiosis; Microsatellite Repeats; Pedigree; Recombination, Genetic
PubMed: 27804967
DOI: 10.1038/hdy.2016.95 -
The Plant Cell Jul 2017
Topics: Chromosomes; Crossing Over, Genetic; DNA Topoisomerases, Type I; Homologous Recombination; Oryza
PubMed: 28716812
DOI: 10.1105/tpc.17.00566