Sex-specific variation in the genome-wide recombination rate

Abstract In most species that reproduce sexually, successful gametogenesis requires recombination during meiosis. The number and placement of crossovers (COs) vary among individuals, with females and males often presenting the most striking contrasts. Despite the recognition that the sexes recombine at different rates (heterochiasmy), existing data fail to answer the question of whether patterns of genetic variation in recombination rate are similar in the two sexes. To fill this gap, we measured the genome-wide recombination rate in both sexes from a panel of wild-derived inbred strains from multiple subspecies of house mice (Mus musculus) and from a few additional species of Mus. To directly compare recombination rates in females and males from the same genetic backgrounds, we applied established methods based on immunolocalization of recombination proteins to inbred strains. Our results reveal discordant patterns of genetic variation in the two sexes. Whereas male genome-wide recombination rates vary substantially among strains, female recombination rates measured in the same strains are more static. The direction of heterochiasmy varies within two subspecies, Mus musculus molossinus and Mus musculus musculus. The direction of sex differences in the length of the synaptonemal complex and CO positions is consistent across strains and does not track sex differences in genome-wide recombination rate. In males, contrasts between strains with high recombination rate and strains with low recombination rate suggest more recombination is associated with stronger CO interference and more double-strand breaks. The sex-specific patterns of genetic variation we report underscore the importance of incorporating sex differences into recombination research.

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Higher Intercellular Variation in Genome-Wide Recombination Rate in Female Mice

Cytogenetic and Genome Research ◽

10.1159/000516998 ◽

2021 ◽

pp. 1-7

Author(s):

April L. Peterson ◽

Bret A. Payseur

Keyword(s):

Natural Selection ◽

Sex Difference ◽

Meiotic Recombination ◽

Recombination Rate ◽

Inbred Strains ◽

House Mice ◽

Mlh1 Focus ◽

Female Mice ◽

Genome Wide ◽

Recombination Pathway

Meiotic recombination affects fertility, shuffles genomes, and modulates the effectiveness of natural selection. Despite conservation of the recombination pathway, the rate of recombination varies among individuals and along chromosomes. Recombination rate also differs among cells from the same organism, but this form of variation has received less attention. To identify patterns that characterize intercellular variation in the genome-wide recombination rate, we counted foci of the MLH1 recombination-associated protein in oocytes and spermatocytes from a panel of wild-derived inbred strains of house mice. Females show higher intercellular variation in MLH1 focus count than males from the same inbred strains. This pattern is consistent across strains from multiple subspecies, including 2 strains in which the average MLH1 focus count is higher in males. The sex difference in genome-wide recombination rate we report suggests that selection targeting recombination rate will be more efficient in males than in females.

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Y-chromosomal DNA polymorphism in mouse inbred strains

Genetics Research ◽

10.1017/s0016672300023351 ◽

1987 ◽

Vol 50 (1) ◽

pp. 69-72 ◽

Cited By ~ 26

Author(s):

Yutaka Nishioka

Keyword(s):

Y Chromosome ◽

Mus Musculus ◽

Dna Polymorphism ◽

Inbred Strains ◽

Laboratory Mice ◽

Wild Populations ◽

Chromosomal Dna ◽

Mus Musculus Musculus

SummaryMice are the most widely used experimental mammals, and many inbred strains are available. However, except for the relatively recent strains derived from known wild populations, the relationships between wild and laboratory mice are not well understood. Based on the Y-chromosomal restriction fragmentlength polymorphism, seventeen inbred strains were classified into two groups: strains with the Mus musculus musculus type Y chromosome and those with the M. m. domesticus type Y chromosome. We extended the survey to an additional twenty-two inbred strains. The M. m. musculus type Y chromosome was found in AEJ/GnLe, AAU/SsJ, BDP/J, BXSB/MpJ, DA/HuSn, HTG/GoSfSn, I/LnJ, LP/J, NZW/LacJ, RIIIS/J, SB/Le, SEA/GnJ, SF/CamEi, SK/CamEi, SM/J, WB/ReJ, WC/ReJ and YBR/Ei, while the M. m. domesticus type Y chromosome was present in BUB/BnJ, MA/MyJ, PL/J and ST/bJ.

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Variation in recombination rate and its genetic determinism in sheep (Ovis Aries) populations from combining multiple genome-wide datasets

10.1101/104976 ◽

2017 ◽

Author(s):

Morgane Petit ◽

Jean-Michel Astruc ◽

Julien Sarry ◽

Laurence Drouilhet ◽

Stéphane Fabre ◽

...

Keyword(s):

Meiotic Recombination ◽

Individual Variation ◽

Recombination Rate ◽

Snp Array ◽

Genetic Determinism ◽

Ovis Aries ◽

Domestic Sheep ◽

Recombination Rates ◽

Male Recombination ◽

Genome Wide

AbstractRecombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and datasets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified about 50,000 crossover hotspots on the genome and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting inter-individual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly 2 other loci of smaller effects including the KCNJ15 and FSHR genes. Finally, we compared our results to those obtained previously in a distantly related population of domestic sheep, the Soay. This comparison revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome and that the two datasets can be combined to create more precise male meiotic recombination maps in sheep. Despite their similar recombination maps, we show that Soay and Lacaune males exhibit different heritabilities and QTL effects for inter-individual variation in genome-wide recombination rates.

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Sex-specific gene expression in the BXD mouse liver

Physiological Genomics ◽

10.1152/physiolgenomics.00110.2009 ◽

2010 ◽

Vol 42 (3) ◽

pp. 456-468 ◽

Cited By ~ 20

Author(s):

Daniel M. Gatti ◽

Ni Zhao ◽

Elissa J. Chesler ◽

Blair U. Bradford ◽

Andrey A. Shabalin ◽

...

Keyword(s):

Gene Expression ◽

Sex Differences ◽

Genetic Variation ◽

Inbred Strains ◽

Major Effect ◽

Specific Gene ◽

Sexually Dimorphic ◽

Expression Data ◽

Data Set ◽

Liver Gene

Differences in clinical phenotypes between the sexes are well documented and have their roots in differential gene expression. While sex has a major effect on gene expression, transcription is also influenced by complex interactions between individual genetic variation and environmental stimuli. In this study, we sought to understand how genetic variation affects sex-related differences in liver gene expression by performing genetic mapping of genomewide liver mRNA expression data in a genetically defined population of naive male and female mice from C57BL/6J, DBA/2J, B6D2F1, and 37 C57BL/6J × DBA/2J (BXD) recombinant inbred strains. As expected, we found that many genes important to xenobiotic metabolism and other important pathways exhibit sexually dimorphic expression. We also performed gene expression quantitative trait locus mapping in this panel and report that the most significant loci that appear to regulate a larger number of genes than expected by chance are largely sex independent. Importantly, we found that the degree of correlation within gene expression networks differs substantially between the sexes. Finally, we compare our results to a recently released human liver gene expression data set and report on important similarities in sexually dimorphic liver gene expression between mouse and human. This study enhances our understanding of sex differences at the genome level and between species, as well as increasing our knowledge of the molecular underpinnings of sex differences in responses to xenobiotics.

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Genetic control of the kinetics of mouse spermatogenesis

Genetics Research ◽

10.1017/s0016672300012945 ◽

1973 ◽

Vol 22 (2) ◽

pp. 155-167 ◽

Cited By ~ 6

Author(s):

W. Robert Bruce ◽

Rudolf Furrer ◽

Robert B. Goldberg ◽

Marvin L. Meistrich ◽

Beatrice Mintz

Keyword(s):

Genetic Control ◽

Mus Musculus ◽

Genetic Factors ◽

Tritiated Thymidine ◽

Inbred Strains ◽

Velocity Sedimentation ◽

Mus Musculus Musculus ◽

Kinetics Of

SUMMARYThe kinetics of spermatogenesis in the mouse, and the possible genetic controls, have been investigated in different genotypes by means of the method of velocity sedimentation at unit gravity to separate testis cells and nuclei labelled with tritiated thymidine. The progression of the radioactivity through different sedimentation classes of cells provides a measure of their kinetics. The results demonstrate kinetic differences at the stage of spermatocyte differentiation between the C57BL/6 and AKR inbred strains of Mus musculus musculus and in randombred mice of the subspecies Mus m. molossinus. These kinetic differences are controlled by genetic factors which are not linked to the Y chromosome. The relevant autosomal alleles of C57BL/6 are dominant over those of AKR in F1 hybrids.

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Sex-Specific Evolution of the Genome-wide Recombination Rate

10.1101/2020.07.08.194191 ◽

2020 ◽

Author(s):

April L. Peterson ◽

Bret A. Payseur

Keyword(s):

Recombination Rate ◽

Rapid Evolution ◽

Double Strand Breaks ◽

Crossing Over ◽

Recombination Rates ◽

Male Recombination ◽

Strand Breaks ◽

Genome Wide ◽

Primary Driver ◽

Evolutionary Trajectories

ABSTRACTAlthough meiotic recombination is required for successful gametogenesis in most species that reproduce sexually, the rate of crossing over varies among individuals. Differences in recombination rate between females and males are perhaps the most striking form of this variation. To determine how sex shapes the evolution of recombination, we directly compared the genome-wide recombination rate in females and males across a common set of genetic backgrounds in house mouse. Our results reveal highly discordant evolutionary trajectories in the two sexes. Whereas male recombination rates show rapid evolution over short timescales, female recombination rates measured in the same strains are mostly static. Strains with high recombination in males have more double-strand breaks and stronger crossover interference than strains with low recombination in males, suggesting that these factors contribute to the sex-specific evolution we document. Our findings provide the strongest evidence yet that sex is a primary driver of recombination rate evolution.

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Allelic profile at 37 biochemical loci of two inbred strains of the house mouse derived from wild Mus musculus musculus

Laboratory Animals ◽

10.1258/002367788780746610 ◽

1988 ◽

Vol 22 (1) ◽

pp. 61-66 ◽

Cited By ~ 10

Author(s):

O. H. Von Deimlingi ◽

J. Forejt ◽

T. F. Wienker

Keyword(s):

Genetic Distance ◽

House Mouse ◽

Genetic Relationship ◽

Mus Musculus ◽

Inbred Strains ◽

Genetic Distances ◽

Allelic Profile ◽

Mus Musculus Musculus

Two newly established inbred strains derived from Mus musculus musculus, designated PWD/Ph (F29) and PWK/Ph (F33), were examined for their alleles at 37 biochemical loci located on 12 different chromosomes. The allelic pattern showed characteristic differences from those observed in common inbred strains. The genetic distance D between PWK/Ph and PWD/Ph was 0·027, whereas the corresponding values for the genetic distances between PWK/Ph and C57BL/6J, DBA/2J, BALB/cJ and SWR/J were 0·777, 0·721, 0·721 and 0·838 respectively. New allozymes are described as being controlled by the loci Es-23, Pre-2 and Tam-1. The genetic relationship to M.m. molossinus is indicated by identical alleles at six other loci ( Es-2, Es-9, Es-10, Es-11, Es-18 and Es-22).

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Selective Sweeps in the Presence of Interference Among Partially Linked Loci

Genetics ◽

10.1093/genetics/164.1.389 ◽

2003 ◽

Vol 164 (1) ◽

pp. 389-398 ◽

Cited By ~ 1

Author(s):

Yuseob Kim ◽

Wolfgang Stephan

Keyword(s):

Genetic Variation ◽

Recombination Rate ◽

Substantial Reduction ◽

Natural Populations ◽

High Rate ◽

Selective Sweeps ◽

Recombination Rates ◽

Analytical Approximations ◽

Fixation Probabilities ◽

Beneficial Allele

Abstract Recurrent directional selection on a partially recombining chromosome may cause a substantial reduction of standing genetic variation in natural populations. Previous studies of this effect, commonly called selective sweeps, assumed that at most one beneficial allele is on the way to fixation at a given time. However, for a high rate of selected substitutions and a low recombination rate, this assumption can easily be violated. We investigated this problem using full-forward simulations and analytical approximations. We found that interference between linked beneficial alleles causes a reduction of their fixation probabilities. The hitchhiking effect on linked neutral variation for a given substitution also slightly decreases due to interference. As a result, the strength of recurrent selective sweeps is weakened. However, this effect is significant only in chromosomal regions of relatively low recombination rates where the level of variation is greatly reduced. Therefore, previous results on recurrent selective sweeps although derived for a restricted parameter range are still valid. Analytical approximations are obtained for the case of complete linkage for which interference between competing beneficial alleles is maximal.

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Evolution and Plasticity of Genome-Wide Meiotic Recombination Rates

Annual Review of Genetics ◽

10.1146/annurev-genet-021721-033821 ◽

2021 ◽

Vol 55 (1) ◽

Author(s):

Ian R. Henderson ◽

Kirsten Bomblies

Keyword(s):

Chromosome Segregation ◽

Meiotic Recombination ◽

Recombination Rate ◽

Empirical Studies ◽

Annual Review ◽

Publication Date ◽

Recombination Rates ◽

Homologous Chromosomes ◽

Genome Wide ◽

Mechanistic Basis

Sex, as well as meiotic recombination between homologous chromosomes, is nearly ubiquitous among eukaryotes. In those species that use it, recombination is important for chromosome segregation during gamete production, and thus for fertility. Strikingly, although in most species only one crossover event per chromosome is required to ensure proper segregation, recombination rates vary considerably above this minimum and show variation within and among species. However, whether this variation in recombination is adaptive or neutral and what might shape it remain unclear. Empirical studies and theory support the idea that recombination is generally beneficial but can also have costs. Here, we review variation in genome-wide recombination rates, explore what might cause this, and discuss what is known about its mechanistic basis. We end by discussing the environmental sensitivity of meiosis and recombination rates, how these features may relate to adaptation, and their implications for a broader understanding of recombination rate evolution. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Background selection under evolving recombination rates

10.1101/2021.12.20.473549 ◽

2021 ◽

Author(s):

Tom R Booker ◽

Bret A Payseur ◽

Anna Tigano

Keyword(s):

Recombination Rate ◽

Purifying Selection ◽

Background Selection ◽

Effective Population ◽

Recombination Rates ◽

Fitness Effects ◽

Deleterious Alleles ◽

Genome Wide ◽

Modern House ◽

Eukaryotic Genomes

Background selection (BGS), the effect that purifying selection exerts on sites linked to deleterious alleles, is expected to be ubiquitous across eukaryotic genomes. The effects of BGS reflect the interplay of the rates and fitness effects of deleterious mutations with recombination. A fundamental assumption of BGS models is that recombination rates are invariant over time. However, in some lineages recombination rates evolve rapidly, violating this central assumption. Here, we investigate how recombination rate evolution affects genetic variation under BGS. We show that recombination rate evolution modifies the effects of BGS in a manner similar to a localised change in the effective population size, potentially leading to an underestimation of the genome-wide effects of selection. Furthermore, we find evidence that recombination rate evolution in the ancestors of modern house mice may have impacted inferences of the genome-wide effects of selection in that species.

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