scholarly journals Background selection under evolving recombination rates

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.

scholarly journals Transition from background selection to associative overdominance promotes diversity in regions of low recombination

2019 ◽  
Author(s):  
Kimberly J. Gilbert ◽  
Fanny Pouyet ◽  
Laurent Excoffier ◽  
Stephan Peischl
Keyword(s):  
Genetic Diversity ◽  
Balancing Selection ◽  
Purifying Selection ◽  
Heterozygote Advantage ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Recombination Rates ◽  
Locus Model ◽  
Genome Wide ◽  
Linked Selection

SummaryLinked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection, BGS, Charlesworth et al. 1993), creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD, Ohta 1971, Zhao & Charlesworth, 2016), due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao & Charlesworth (2016) identified the conditions when AOD should dominate over BGS in a single-locus model and suggested that the effect of AOD could become stronger if multiple linked deleterious variants co-segregate. We present a model describing how and under which conditions multi-locus dynamics can amplify the effects of AOD. We derive the conditions for a transition from BGS to AOD due to pseudo-overdominance (Ohta & Kimura 1970), i.e. a form of balancing selection that maintains complementary deleterious haplotypes that mask the effect of recessive deleterious mutations. Simulations confirm these findings and show that multi-locus AOD can increase diversity in low recombination regions much more strongly than previously appreciated. While BGS is known to drive genome-wide diversity in humans (Pouyet et al. 2018), the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 21 such regions in the human genome showing clear signals of multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low recombination regions of many species.

scholarly journals Large Number of Replacement Polymorphisms in Rapidly Evolving Genes of Drosophila: Implications for Genome-Wide Surveys of DNA Polymorphism

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1717-1729 ◽  
Author(s):  
Karl J Schmid ◽  
Loredana Nigro ◽  
Charles F Aquadro ◽  
Diethard Tautz
Keyword(s):  
Recombination Rate ◽  
Current Knowledge ◽  
Purifying Selection ◽  
Neutral Evolution ◽  
Nucleotide Polymorphism ◽  
Effective Population ◽  
Nucleotide Substitutions ◽  
Large Numbers ◽  
Genome Wide ◽  
Population Sizes

AbstractWe present a survey of nucleotide polymorphism of three novel, rapidly evolving genes in populations of Drosophila melanogaster and D. simulans. Levels of silent polymorphism are comparable to other loci, but the number of replacement polymorphisms is higher than that in most other genes surveyed in D. melanogaster and D. simulans. Tests of neutrality fail to reject neutral evolution with one exception. This concerns a gene located in a region of high recombination rate in D. simulans and in a region of low recombination rate in D. melanogaster, due to an inversion. In the latter case it shows a very low number of polymorphisms, presumably due to selective sweeps in the region. Patterns of nucleotide polymorphism suggest that most substitutions are neutral or nearly neutral and that weak (positive and purifying) selection plays a significant role in the evolution of these genes. At all three loci, purifying selection of slightly deleterious replacement mutations appears to be more efficient in D. simulans than in D. melanogaster, presumably due to different effective population sizes. Our analysis suggests that current knowledge about genome-wide patterns of nucleotide polymorphism is far from complete with respect to the types and range of nucleotide substitutions and that further analysis of differences between local populations will be required to understand the forces more completely. We note that rapidly diverging and nearly neutrally evolving genes cannot be expected only in the genome of Drosophila, but are likely to occur in large numbers also in other organisms and that their function and evolution are little understood so far.

scholarly journals Microsatellite Variation and Recombination Rate in the Human Genome

Genetics ◽  
2000 ◽  
Vol 156 (3) ◽  
pp. 1285-1298 ◽  
Author(s):  
Bret A Payseur ◽  
Michael W Nachman
Keyword(s):  
Recombination Rate ◽  
Microsatellite Polymorphism ◽  
Published Data ◽  
Strong Positive Correlation ◽  
Background Selection ◽  
Recombination Rates ◽  
Microsatellite Variation ◽  
Positive Correlation ◽  
Genome Recombination ◽  
Neutral Mutations

Abstract Background (purifying) selection on deleterious mutations is expected to remove linked neutral mutations from a population, resulting in a positive correlation between recombination rate and levels of neutral genetic variation, even for markers with high mutation rates. We tested this prediction of the background selection model by comparing recombination rate and levels of microsatellite polymorphism in humans. Published data for 28 unrelated Europeans were used to estimate microsatellite polymorphism (number of alleles, heterozygosity, and variance in allele size) for loci throughout the genome. Recombination rates were estimated from comparisons of genetic and physical maps. First, we analyzed 61 loci from chromosome 22, using the complete sequence of this chromosome to provide exact physical locations. These 61 microsatellites showed no correlation between levels of variation and recombination rate. We then used radiation-hybrid and cytogenetic maps to calculate recombination rates throughout the genome. Recombination rates varied by more than one order of magnitude, and most chromosomes showed significant suppression of recombination near the centromere. Genome-wide analyses provided no evidence for a strong positive correlation between recombination rate and polymorphism, although analyses of loci with at least 20 repeats suggested a weak positive correlation. Comparisons of microsatellites in lowest-recombination and highest-recombination regions also revealed no difference in levels of polymorphism. Together, these results indicate that background selection is not a major determinant of microsatellite variation in humans.

scholarly journals Heterogeneity in effective size across the genome: effects on the Inverse Instantaneous Coalescence Rate (IICR) and implications for demographic inference under linked selection.

2021 ◽  
Author(s):  
Simon Boitard ◽  
Armando Arredondo ◽  
Camille Noûs ◽  
Lounes Chikhi ◽  
Olivier Mazet
Keyword(s):  
Genetic Diversity ◽  
Balancing Selection ◽  
Effective Population ◽  
Recombination Rates ◽  
Genome Wide ◽  
Coalescence Rate ◽  
Demographic Inference ◽  
The Impact ◽  
Linked Selection ◽  
Coalescence Times

The relative contribution of selection and neutrality in shaping species genetic diversity is one of the most central and controversial questions in evolutionary theory. Genomic data provide growing evidence that linked selection, i.e. the modification of genetic diversity at neutral sites through linkage with selected sites, might be pervasive over the genome. Several studies proposed that linked selection could be modelled as first approximation by a local reduction (e.g. purifying selection, selective sweeps) or increase (e.g. balancing selection) of effective population size (Ne). At the genome-wide scale, this leads to a large variance of Ne from one region to another, reflecting the heterogeneity of selective constraints and recombination rates between regions. We investigate here the consequences of this variation of Ne on the genome-wide distribution of coalescence times. The underlying motivation concerns the impact of linked selection on demographic inference, because the distribution of coalescence times is at the heart of several important demographic inference approaches. Using the concept of Inverse Instantaneous Coalescence Rate, we demonstrate that in a panmictic population, linked selection always results in a spurious apparent decrease of Ne along time. Balancing selection has a particularly large effect, even when it concerns a very small part of the genome. We quantify the expected magnitude of the spurious decrease of Ne in humans and Drosophila melanogaster, based on Ne distributions inferred from real data in these species. We also find that the effect of linked selection can be significantly reduced by that of population structure.

scholarly journals Background selection and biased gene conversion affect more than 95% of the human genome and bias demographic inferences

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Fanny Pouyet ◽  
Simon Aeschbacher ◽  
Alexandre Thiéry ◽  
Laurent Excoffier
Keyword(s):  
Gene Conversion ◽  
Purifying Selection ◽  
Genomic Diversity ◽  
Background Selection ◽  
Recombination Rates ◽  
Biased Gene Conversion ◽  
Synonymous Sites ◽  
History Of ◽  
Demographic Inference ◽  
Genomic Regions

Disentangling the effect on genomic diversity of natural selection from that of demography is notoriously difficult, but necessary to properly reconstruct the history of species. Here, we use high-quality human genomic data to show that purifying selection at linked sites (i.e. background selection, BGS) and GC-biased gene conversion (gBGC) together affect as much as 95% of the variants of our genome. We find that the magnitude and relative importance of BGS and gBGC are largely determined by variation in recombination rate and base composition. Importantly, synonymous sites and non-transcribed regions are also affected, albeit to different degrees. Their use for demographic inference can lead to strong biases. However, by conditioning on genomic regions with recombination rates above 1.5 cM/Mb and mutation types (C↔G, A↔T), we identify a set of SNPs that is mostly unaffected by BGS or gBGC, and that avoids these biases in the reconstruction of human history.

scholarly journals Determinants of the Efficacy of Natural Selection on Coding and Noncoding Variability in Two Passerine Species

2017 ◽  
Vol 9 (11) ◽  
pp. 2987-3007 ◽  
Author(s):  
Pádraic Corcoran ◽  
Toni I Gossmann ◽  
Henry J Barton ◽  
Jon Slate ◽  
Kai Zeng ◽  
...  
Keyword(s):  
Zebra Finch ◽  
Recombination Rate ◽  
Nucleotide Diversity ◽  
Purifying Selection ◽  
Great Tit ◽  
Untranslated Regions ◽  
Demographic Model ◽  
Zebra Finches ◽  
Effective Population ◽  
Biased Gene Conversion

Abstract Population genetic theory predicts that selection should be more effective when the effective population size (Ne) is larger, and that the efficacy of selection should correlate positively with recombination rate. Here, we analyzed the genomes of ten great tits and ten zebra finches. Nucleotide diversity at 4-fold degenerate sites indicates that zebra finches have a 2.83-fold larger Ne. We obtained clear evidence that purifying selection is more effective in zebra finches. The proportion of substitutions at 0-fold degenerate sites fixed by positive selection (α) is high in both species (great tit 48%; zebra finch 64%) and is significantly higher in zebra finches. When α was estimated on GC-conservative changes (i.e., between A and T and between G and C), the estimates reduced in both species (great tit 22%; zebra finch 53%). A theoretical model presented herein suggests that failing to control for the effects of GC-biased gene conversion (gBGC) is potentially a contributor to the overestimation of α, and that this effect cannot be alleviated by first fitting a demographic model to neutral variants. We present the first estimates in birds for α in the untranslated regions, and found evidence for substantial adaptive changes. Finally, although purifying selection is stronger in high-recombination regions, we obtained mixed evidence for α increasing with recombination rate, especially after accounting for gBGC. These results highlight that it is important to consider the potential confounding effects of gBGC when quantifying selection and that our understanding of what determines the efficacy of selection is incomplete.

scholarly journals Background selection as null hypothesis in population genomics: insights and challenges from Drosophila studies

2017 ◽  
Vol 372 (1736) ◽  
pp. 20160471 ◽  
Author(s):  
Josep M. Comeron
Keyword(s):  
Null Hypothesis ◽  
Population Genomics ◽  
Balancing Selection ◽  
Large Fraction ◽  
Null Model ◽  
Rate Variation ◽  
Background Selection ◽  
Effective Population ◽  
Recombination Rates ◽  
Genome Annotations

The consequences of selection at linked sites are multiple and widespread across the genomes of most species. Here, I first review the main concepts behind models of selection and linkage in recombining genomes, present the difficulty in parametrizing these models simply as a reduction in effective population size ( N e ) and discuss the predicted impact of recombination rates on levels of diversity across genomes. Arguments are then put forward in favour of using a model of selection and linkage with neutral and deleterious mutations (i.e. the background selection model, BGS) as a sensible null hypothesis for investigating the presence of other forms of selection, such as balancing or positive. I also describe and compare two studies that have generated high-resolution landscapes of the predicted consequences of selection at linked sites in Drosophila melanogaster . Both studies show that BGS can explain a very large fraction of the observed variation in diversity across the whole genome, thus supporting its use as null model. Finally, I identify and discuss a number of caveats and challenges in studies of genetic hitchhiking that have been often overlooked, with several of them sharing a potential bias towards overestimating the evidence supporting recent selective sweeps to the detriment of a BGS explanation. One potential source of bias is the analysis of non-equilibrium populations: it is precisely because models of selection and linkage predict variation in N e across chromosomes that demographic dynamics are not expected to be equivalent chromosome- or genome-wide. Other challenges include the use of incomplete genome annotations, the assumption of temporally stable recombination landscapes, the presence of genes under balancing selection and the consequences of ignoring non-crossover (gene conversion) recombination events. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.

scholarly journals Variable signatures of selection despite conserved recombination landscapes early in speciation

2021 ◽  
Author(s):  
Sheela P Turbek ◽  
Georgy A Semenov ◽  
Erik D Enbody ◽  
Leonardo Campagna ◽  
Scott A Taylor
Keyword(s):  
Recombination Rate ◽  
Ficedula Albicollis ◽  
Background Selection ◽  
Recombination Rates ◽  
Heterogeneous Landscapes ◽  
Motacilla Alba ◽  
Genomic Divergence ◽  
Rapid Diversification ◽  
Signatures Of Selection ◽  
Homogeneous Background

Abstract Recently diverged taxa often exhibit heterogeneous landscapes of genomic differentiation, characterized by regions of elevated differentiation on an otherwise homogeneous background. While divergence peaks are generally interpreted as regions responsible for reproductive isolation, they can also arise due to background selection, selective sweeps unrelated to speciation, and variation in recombination and mutation rates. To investigate the association between patterns of recombination and landscapes of genomic differentiation during the early stages of speciation, we generated fine-scale recombination maps for six southern capuchino seedeaters (Sporophila) and two subspecies of White Wagtail (Motacilla alba), two recent avian radiations in which divergent selection on pigmentation genes has likely generated peaks of differentiation. We compared these recombination maps to those of Collared (Ficedula albicollis) and Pied Flycatchers (Ficedula hypoleuca), non-sister taxa characterized by moderate genomic divergence and a heterogenous landscape of genomic differentiation shaped in part by background selection. Although recombination landscapes were conserved within all three systems, we documented a weaker negative correlation between recombination rate and genomic differentiation in the recent radiations. All divergence peaks between capuchinos, wagtails, and flycatchers were located in regions with lower-than-average recombination rates, and most divergence peaks in capuchinos and flycatchers fell in regions of exceptionally reduced recombination. Thus, co-adapted allelic combinations in these regions may have been protected early in divergence, facilitating rapid diversification. Despite largely conserved recombination landscapes, divergence peaks are specific to each focal comparison in capuchinos, suggesting that regions of elevated differentiation have not been generated by variation in recombination rate alone.

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

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.

Sign in / Sign up

Export Citation Format

Share Document