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

2021 ◽  
pp. 1-7
Author(s):  
April L. Peterson ◽  
Bret A. Payseur

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.

2020 ◽  
Vol 30 (8) ◽  
pp. 1517-1528.e6 ◽  
Author(s):  
Kieran Samuk ◽  
Brenda Manzano-Winkler ◽  
Kathryn R. Ritz ◽  
Mohamed A.F. Noor

2019 ◽  
Author(s):  
Kieran Samuk ◽  
Brenda Manzano-Winkler ◽  
Kathryn R. Ritz ◽  
Mohamed A.F. Noor

AbstractWhile recombination is widely recognized to be a key modulator of numerous evolutionary phenomena, we have a poor understanding of how recombination rate itself varies and evolves within a species. Here, we performed a comprehensive study of recombination rate (rate of meiotic crossing over) in two natural populations of Drosophila pseudoobscura from Utah and Arizona, USA. We used an amplicon sequencing approach to obtain high-quality genotypes in approximately 8000 individual backcrossed offspring (17 mapping populations with roughly 530 individuals each), for which we then quantified crossovers. Interestingly, variation in recombination rate within and between populations largely manifested as differences in genome-wide recombination rate rather than remodeling of the local recombination landscape. Comparing populations, we discovered individuals from the Utah population displayed on average 8% higher crossover rates than the Arizona population, a statistically significant difference. Using a QST-FST analysis, we found that this difference in crossover rate was dramatically higher than expected under neutrality, indicating that this difference may have been driven by natural selection. Finally, using a combination of short and long read whole-genome sequencing, we found no significant association between crossover rate and structural variation at the 200-400kb scale. Our results demonstrate that (1) there is abundant variation in genome-wide crossover rate in natural populations (2) interpopulation differences in recombination rate may be the result of local adaptation, and (3) the observed variation among individuals in recombination rate is primarily driven by global regulators of crossover rate, with little detected variation in recombination rate among strains across specific tracts of individual chromosomes.


2017 ◽  
Author(s):  
Morgane Petit ◽  
Jean-Michel Astruc ◽  
Julien Sarry ◽  
Laurence Drouilhet ◽  
Stéphane Fabre ◽  
...  

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.


Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
pp. 1-11
Author(s):  
April L Peterson ◽  
Bret A Payseur

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.


2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Ian R. Henderson ◽  
Kirsten Bomblies

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.


2020 ◽  
Author(s):  
J. Gierten ◽  
T. Fitzgerald ◽  
F. Loosli ◽  
M. Gorenflo ◽  
E. Birney ◽  
...  

Genetics ◽  
2002 ◽  
Vol 162 (1) ◽  
pp. 297-306 ◽  
Author(s):  
Kara E Koehler ◽  
Jonathan P Cherry ◽  
Audrey Lynn ◽  
Patricia A Hunt ◽  
Terry J Hassold

AbstractGenetic background effects on the frequency of meiotic recombination have long been suspected in mice but never demonstrated in a systematic manner, especially in inbred strains. We used a recently described immunostaining technique to assess meiotic exchange patterns in male mice. We found that among four different inbred strains—CAST/Ei, A/J, C57BL/6, and SPRET/Ei—the mean number of meiotic exchanges per cell and, thus, the recombination rates in these genetic backgrounds were significantly different. These frequencies ranged from a low of 21.5 exchanges in CAST/Ei to a high of 24.9 in SPRET/Ei. We also found that, as expected, these crossover events were nonrandomly distributed and displayed positive interference. However, we found no evidence for significant differences in the patterns of crossover positioning between strains with different exchange frequencies. From our observations of >10,000 autosomal synaptonemal complexes, we conclude that achiasmate bivalents arise in the male mouse at a frequency of 0.1%. Thus, special mechanisms that segregate achiasmate chromosomes are unlikely to be an important component of mammalian male meiosis.


Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 595-608 ◽  
Author(s):  
Jody Hey ◽  
Richard M Kliman

AbstractIn Drosophila, as in many organisms, natural selection leads to high levels of codon bias in genes that are highly expressed. Thus codon bias is an indicator of the intensity of one kind of selection that is experienced by genes and can be used to assess the impact of other genomic factors on natural selection. Among 13,000 genes in the Drosophila genome, codon bias has a slight positive, and strongly significant, association with recombination—as expected if recombination allows natural selection to act more efficiently when multiple linked sites segregate functional variation. The same reasoning leads to the expectation that the efficiency of selection, and thus average codon bias, should decline with gene density. However, this prediction is not confirmed. Levels of codon bias and gene expression are highest for those genes in an intermediate range of gene density, a pattern that may be the result of a tradeoff between the advantages for gene expression of close gene spacing and disadvantages arising from regulatory conflicts among tightly packed genes. These factors appear to overlay the more subtle effect of linkage among selected sites that gives rise to the association between recombination rate and codon bias.


Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 621-641 ◽  
Author(s):  
Dawn A Thompson ◽  
Franklin W Stahl

AbstractMeiotic exchange occurs preferentially between homologous chromatids, in contrast to mitotic recombination, which occurs primarily between sister chromatids. To identify functions that direct meiotic recombination events to homologues, we screened for mutants exhibiting an increase in meiotic unequal sister-chromatid recombination (SCR). The msc (meiotic sister-chromatid recombination) mutants were quantified in spo13 meiosis with respect to meiotic unequal SCR frequency, disome segregation pattern, sporulation frequency, and spore viability. Analysis of the msc mutants according to these criteria defines three classes. Mutants with a class I phenotype identified new alleles of the meiosis-specific genes RED1 and MEK1, the DNA damage checkpoint genes RAD24 and MEC3, and a previously unknown gene, MSC6. The genes RED1, MEK1, RAD24, RAD17, and MEC1 are required for meiotic prophase arrest induced by a dmc1 mutation, which defines a meiotic recombination checkpoint. Meiotic unequal SCR was also elevated in a rad17 mutant. Our observation that meiotic unequal SCR is elevated in meiotic recombination checkpoint mutants suggests that, in addition to their proposed monitoring function, these checkpoint genes function to direct meiotic recombination events to homologues. The mutants in class II, including a dmc1 mutant, confer a dominant meiotic lethal phenotype in diploid SPO13 meiosis in our strain background, and they identify alleles of UBR1, INP52, BUD3, PET122, ELA1, and MSC1-MSC3. These results suggest that DMC1 functions to bias the repair of meiosis-specific double-strand breaks to homologues. We hypothesize that the genes identified by the class II mutants function in or are regulators of the DMC1-promoted interhomologue recombination pathway. Class III mutants may be elevated for rates of both SCR and homologue exchange.


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