The rate of meiotic gene conversion varies by sex and age

Halldórsson, Bjarni V.; Hardarson, Marteinn T.; Kehr, Birte; Styrkársdóttir, Unnur; Gylfason, Arnaldur; Þorleifsson, Guðmar; Zink, Florian; Jónasdóttir, Aðalbjörg; Jónasdóttir, Áslaug; Sulem, Patrick; Másson, Gísli; Þorsteinsdóttir, Unnur; Helgason, Agnar; Kong, Augustine; Guðbjartsson, Daníel F.; Stefánsson, Kári

doi:10.1038/ng.3669

Cited by 88 publications

(158 citation statements)

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“…Despite the agedness of Y-palindromes, comparative sequencing of primate Ypalindromes revealed lower levels of sequence divergence between paralogous palindrome arms (within a species) than between orthologous arms (between species), suggesting that ongoing arm-to-arm gene conversion homogenizes the sequence within in paralogous palindrome arms (Rozen, et al 2003). Primate Y-palindrome arm-to-arm gene conversion is estimated to be 3X higher than allelic gene conversion (Rozen, et al 2003;Halldorsson, et al 2016). Since most of the Y chromosome does not recombine with the X chromosome, Ypalindrome arm-to-arm gene conversion has been proposed to maintain the sequence integrity of the testis-specific genes harbored within Y-palindromes (Rozen, et al 2003;.…”

Section: Main Textmentioning

confidence: 97%

Large X-linked palindromes undergo arm-to-arm gene conversion across Mus lineages

Swanepoel

Gerlinger

Mueller

2019

Preprint

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Large (>10kb), nearly-identical (>99% nucleotide identity), palindromic sequences are enriched on mammalian sex chromosomes. Primate Y-palindromes undergo high rates of arm-to-arm gene conversion, a proposed mechanism for maintaining their sequence integrity in the absence of X-Y recombination. It is unclear whether X-palindromes, which can freely recombine in females, undergo arm-to-arm gene conversion and, if so, at what rate. We generated highquality sequence assemblies of Mus molossinus and Mus spretus X-palindromic regions and compared them to orthologous Mus musculus X-palindromes. Our evolutionary sequence comparisons found evidence of X-palindrome arm-to-arm gene conversion at rates comparable to rates of autosomal allelic gene conversion in mice. Mus X-palindrome genes also exhibit higher than expected sequence diversification, indicating gene conversion may facilitate the rapid evolution of palindrome-associated genes. We conclude that in addition to maintaining genes' sequence integrity via sequence homogenization, arm-to-arm gene conversion can also rapidly drive genetic evolution via sequence diversification.

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Section: Main Textmentioning

confidence: 97%

Large X-linked palindromes undergo arm-to-arm gene conversion across Mus lineages

Swanepoel

Gerlinger

Mueller

2019

Preprint

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“…Finally, human NCO events show a strong overall bias towards G/C bases (68%) 18,19 , as opposed to A/T bases [20][21][22] , occurring via an unknown mechanism. This phenomenon is thought to have driven regional differences in the GC-content of many species genome-wide [23][24][25] .…”

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confidence: 99%

“…Furthermore, many fundamental questions remain about the process of non-crossover recombination itself, due to the difficulty of detecting NCO events. Previous studies in humans 18,19 have revealed that in males, most (~70%) NCO events occur within PRDM9positioned recombination hotspots, and are short (<1 kb) and simple: they comprise contiguous tracts of converted SNPs, with no non-converted SNPs amongst them. In contrast, in females, a large number of "complex" NCO events, often extending over 1 kb, are seen.…”

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confidence: 99%

A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination

Bitoun

Altemose

et al. 2018

Preprint

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During meiotic recombination in most mammals, hundreds of programmed DNA Double-Strand Breaks (DSBs) occur across all chromosomes in each cell at sites bound by the protein PRDM9.Faithful DSB repair using the homologous chromosome is essential for fertility, yielding either non-crossovers, which are frequent but difficult to detect, or crossovers. In certain hybrid mice, high sequence divergence causes PRDM9 to bind each homologue at different sites, "asymmetrically", and these mice exhibit meiotic failure and infertility, by unknown mechanisms. To investigate the impact of local sequence divergence on recombination, we intercrossed two mouse subspecies over five generations and deep-sequenced 119 offspring, whose high heterozygosity allowed detection of thousands of crossover and non-crossover events with unprecedented power and spatial resolution. Both crossovers and non-crossovers are strongly depleted at individual asymmetric sites, revealing that PRDM9 not only positions DSBs but also promotes their homologous repair by binding to the unbroken homologue at each site.Unexpectedly, we found that non-crossovers containing multiple mismatches repair by a different mechanism than single-mismatch sites, which undergo GC-biased gene conversion.These results demonstrate that local genetic diversity profoundly alters meiotic repair pathway decisions via at least two distinct mechanisms, impacting genome evolution and Prdm9-related hybrid infertility.3 Main TextDuring meiosis, genetic information is exchanged between homologous chromosomes via the process of recombination. In mammals and other species, recombination is essential for the proper pairing of homologous chromosomes (synapsis) and their segregation into gametes, and together with mutation generates all genetic variation 1,2 . In many species, most recombination events cluster into small 1-2 kb regions of the genome, called recombination hotspots. In mice and humans, these hotspots are positioned mainly by PRDM9 3-8 , a zinc-finger protein that binds specific sequence motifs and deposits at least two histone modifications, H3K4me3 and H3K36me3 9,10 , on the surrounding nucleosomes. Double-Strand Breaks (DSBs) subsequently form near a small subset of PRDM9 binding sites in each cell 11 , and DSB processing results in single-stranded DNA decorated with the strand exchange proteins RAD51 and DMC1 7 . Each DSB can ultimately repair by homologous recombination in several ways (Fig. 1a). Because meiotic DSBs occur following replication of DNA, some DSBs can repair invisibly, using the sister chromatid as a repair template, although this process is disfavoured 12 . One exception is on the X chromosome in males, which has no homologue and instead repairs from its sister chromatid later in meiotic prophase 12 . The genetic features used for precise identification of the appropriate homologous DNA, to facilitate this repair, remain unknown. A minority of DSBs form crossovers (COs), involving reciprocal exchanges between homologues, while many more DSBs become non-cros...

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“…A minimum of one CO per chromosome during meiosis is a requirement for proper chromosome segregation (Pardo-Manuel De Villena and Sapienza, 2001). When both COs and NCOs are resolved, they can also give rise to gene conversions (GCs) as a mechanism of DSB repair involving the non-reciprocal transfer of short DNA segments between homologous non-sister chromatids (Sun et al, 2012;Halldorsson et al, 2016). GCs can be…”

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confidence: 99%

Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency

Gardiner

Wingen

Bailey

et al. 2019

Preprint

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Sequence exchange between homologous chromosomes through crossing over and gene conversion is highly conserved among eukaryotes, contributing to genome stability and genetic diversity. Lack of recombination limits breeding efforts in crops, therefore increasing recombination rates can reduce linkage-drag and generate new genetic combinations. We use computational analysis of 13 recombinant inbred mapping populations to assess crossover and gene conversion frequency in the hexaploid genome of wheat (Triticum aestivum). We observe that high frequency crossover sites are shared between populations and that closely related parental founders lead to populations with more similar crossover patterns. We demonstrate that gene conversion is more prevalent and covers more of the genome in wheat than in other plants, making it a critical process in the generation of new haplotypes, particularly in centromeric regions where crossovers are rare. We have identified QTL for altered gene conversion and crossover frequency and confirm functionality for a novel RecQ helicase gene that belongs to an ancient clade that is missing in some plant lineages including Arabidopsis. This is the first gene to be demonstrated to be involved in gene conversion in wheat. Harnessing the RecQ helicase has the potential to break linkage-drag utilizing widespread gene conversions. Main Text:There is an evolutionary requirement for genetic diversity across a species. Shuffling of material between homologous chromosomes, or genetic recombination, breaks linkage between genes resulting in offspring that have combinations of alleles that differ from those found in either of the parents. During meiosis, double-strand breaks (DSBs) can generate sequence variation in gametes via the DSB repair model (Szostak et al., 1983). DSBs are resolved either by homologous recombination as crossovers (COs) i.e. the reciprocal exchange of large regions between chromosomes, or otherwise as non-crossovers (NCOs). A minimum of one CO per chromosome during meiosis is a requirement for proper chromosome segregation (Pardo-Manuel De Villena and Sapienza, 2001). When both COs and NCOs are resolved, they can also give rise to gene conversions (GCs) as a mechanism of DSB repair involving the non-reciprocal transfer of short DNA segments between homologous non-sister chromatids (Sun et al., 2012;Halldorsson et al., 2016). GCs can be

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The rate of meiotic gene conversion varies by sex and age

Cited by 88 publications

References 55 publications

Large X-linked palindromes undergo arm-to-arm gene conversion across Mus lineages

Large X-linked palindromes undergo arm-to-arm gene conversion across Mus lineages

A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination

Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency

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