DILS: Demographic inferences with linked selection by using ABC

Abstract Selected substitutions at one locus can induce stochastic dynamics that resemble genetic drift at a closely linked neutral locus. The pseudohitchhiking model is a one-locus model that approximates these effects and can be used to describe the major consequences of linked selection. As the changes in neutral allele frequencies when hitchhiking are rapid, diffusion theory is not appropriate for studying neutral dynamics. A stationary distribution and some results on substitution processes are presented that use the theory of continuous-time Markov processes with discontinuous sample paths. The coalescent of the pseudohitchhiking model is shown to have a random number of branches at each node, which leads to a frequency spectrum that is different from that of the equilibrium neutral model. If genetic draft, the name given to these induced stochastic effects, is a more important stochastic force than genetic drift, then a number of paradoxes that have plagued population genetics disappear.

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The genomic landscape of recombination rate variation in Chlamydomonas reinhardtii reveals a pronounced effect of linked selection

10.1101/340992 ◽

2018 ◽

Cited By ~ 1

Author(s):

Ahmed R. Hasan ◽

Rob W. Ness

Keyword(s):

Chlamydomonas Reinhardtii ◽

Recombination Rate ◽

Natural Populations ◽

Gc Content ◽

Sexual Cycle ◽

Rate Variation ◽

Effective Population ◽

Entire Genome ◽

Recombination Rate Variation ◽

Linked Selection

AbstractRecombination confers a major evolutionary advantage by breaking up linkage disequilibrium (LD) between harmful and beneficial mutations and facilitating selection. Here, we use genome-wide patterns of LD to infer fine-scale recombination rate variation in the genome of the model green alga Chlamydomonas reinhardtii and estimate rates of LD decay across the entire genome. We observe recombination rate variation of up to two orders of magnitude, finding evidence of recombination hotspots playing a role in the genome. Recombination rate is highest just upstream of genic regions, suggesting the preferential targeting of recombination breakpoints in promoter regions. Furthermore, we observe a positive correlation between GC content and recombination rate, suggesting a role for GC-biased gene conversion or selection on base composition within the GC-rich genome of C. reinhardtii. We also find a positive relationship between nucleotide diversity and recombination, consistent with widespread influence of linked selection in the genome. Finally, we use estimates of the effective rate of recombination to calculate the rate of sex that occurs in natural populations of this important model microbe, estimating a sexual cycle roughly every 770 generations. We argue that the relatively infrequent rate of sex and large effective population size creates an population genetic environment that increases the influence of linked selection on the genome.

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Linked selection shapes the landscape of genomic variation in three oak species

New Phytologist ◽

10.1111/nph.17793 ◽

2021 ◽

Author(s):

Yi‐Ye Liang ◽

Yong Shi ◽

Shuai Yuan ◽

Biao‐Feng Zhou ◽

Xue‐Yan Chen ◽

...

Keyword(s):

Genomic Variation ◽

Linked Selection

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The demography and population genomics of evolutionary transitions to self-fertilization in plants

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0344 ◽

2014 ◽

Vol 369 (1648) ◽

pp. 20130344 ◽

Cited By ~ 53

Author(s):

Spencer C. H. Barrett ◽

Ramesh Arunkumar ◽

Stephen I. Wright

Keyword(s):

Mating System ◽

Population Genomics ◽

Molecular Data ◽

Reproductive Assurance ◽

Evolutionary Transitions ◽

Cast Doubt ◽

Self Fertilization ◽

Loss Of Diversity ◽

Linked Selection

The evolution of self-fertilization from outcrossing has occurred on numerous occasions in flowering plants. This shift in mating system profoundly influences the morphology, ecology, genetics and evolution of selfing lineages. As a result, there has been sustained interest in understanding the mechanisms driving the evolution of selfing and its environmental context. Recently, patterns of molecular variation have been used to make inferences about the selective mechanisms associated with mating system transitions. However, these inferences can be complicated by the action of linked selection following the transition. Here, using multilocus simulations and comparative molecular data from related selfers and outcrossers, we demonstrate that there is little evidence for strong bottlenecks associated with initial transitions to selfing, and our simulation results cast doubt on whether it is possible to infer the role of bottlenecks associated with reproductive assurance in the evolution of selfing. They indicate that the effects of background selection on the loss of diversity and efficacy of selection occur rapidly following the shift to high selfing. Future comparative studies that integrate explicit ecological and genomic details are necessary for quantifying the independent and joint effects of selection and demography on transitions to selfing and the loss of genetic diversity.

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

10.1101/748004 ◽

2019 ◽

Cited By ~ 5

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.

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SIMULATION OF X-LINKED SELECTION IN DROSOPHILA

Genetics ◽

10.1093/genetics/83.3.551 ◽

1976 ◽

Vol 83 (3) ◽

pp. 551-571

Author(s):

Philip W Hedrick

Keyword(s):

Gene Frequency ◽

Frequency Change ◽

Wild Type ◽

Weak Selection ◽

Gene Frequencies ◽

Linked Gene ◽

Males And Females ◽

Genetic Simulation ◽

Linked Selection ◽

Best Fit

ABSTRACT The change in gene frequency for two X-linked mutants, y and w, in a number of experiments was compared to that predicted from a genetic simulation program which utilized estimated differences in relative mating ability, fecundity, and viability. The simulation gave excellent predictions of gene frequency change even when experiments were started with different initial gene frequencies in the males and females or when the two loci were segregating simultaneously. The rate of elimination was slower when there were unequal initial gene frequencies than when males and females had equal initial gene frequencies. Simulation demonstrated that this was a general phenomenon when there is strong selection but that the opposite is true for weak selection. In two other experiments, the mating advantage of wild-type males was balanced by a fecundity advantage in mutant females. In all four replicates of both experiments, the mutant was maintained for several generations at the high initial frequency but then decreased quickly and was eliminated. Results obtained restarting one of these experiments with flies from a generation after the decline in gene frequency indicated that a linked gene and not frequency-dependent selection was responsible for the unpredictable gene-frequency change in the mutant. Using a least squares technique, it was found that a recessive fecundity locus 15 map units from the w locus gave the best fit for bothexperiments.

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Genetic diversity on the human X chromosome does not support a strict pseudoautosomal boundary

10.1101/033936 ◽

2015 ◽

Author(s):

Daniel J Cotter ◽

Sarah M Brotman ◽

Melissa A Wilson Sayres

Keyword(s):

Genetic Diversity ◽

X Chromosome ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Gradual Reduction ◽

Noncoding Regions ◽

Pseudoautosomal Regions ◽

Linked Selection ◽

Human Specific ◽

Pseudoautosomal Boundary

Unlike the autosomes, recombination between the X chromosome and Y chromosome often thought to be constrained to two small pseudoautosomal regions (PARs) at the tips of each sex chromosome. The PAR1 spans the first 2.7 Mb of the proximal arm of the human sex chromosomes, while the much smaller PAR2 encompasses the distal 320 kb of the long arm of each sex chromosome. In addition to the PAR1 and PAR2, there is a human-specific X-transposed region that was duplicated from the X to the Y. The X-transposed region is often not excluded from X-specific analyses, unlike the PARs, because it is not thought to routinely recombine. Genetic diversity is expected to be higher in recombining regions than in non-recombining regions because recombination reduces the effect of linked selection. In this study, we investigate patterns of genetic diversity in noncoding regions across the entire X chromosome of a global sample of 26 unrelated genetic females. We observe that genetic diversity in the PAR1 is significantly greater than the non-recombining regions (nonPARs). However, rather than an abrupt drop in diversity at the pseudoautosomal boundary, there is a gradual reduction in diversity from the recombining through the non-recombining region, suggesting that recombination between the human sex chromosomes spans across the currently defined pseudoautosomal boundary. In contrast, diversity in the PAR2 is not significantly elevated compared to the nonPAR, suggesting that recombination is not obligatory in the PAR2. Finally, diversity in the X-transposed region is higher than the surrounding nonPAR regions, providing evidence that recombination may occur with some frequency between the X and Y in the XTR.

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Quantifying the relationship between genetic diversity and population size suggests natural selection cannot explain Lewontin's paradox

eLife ◽

10.7554/elife.67509 ◽

2021 ◽

Vol 10 ◽

Author(s):

Vince Buffalo

Keyword(s):

Genetic Diversity ◽

Population Size ◽

Phylogenetic Signal ◽

Neutral Theory ◽

Negative Relationship ◽

Abundant Species ◽

Census Size ◽

Population Sizes ◽

The Relationship ◽

Linked Selection

Neutral theory predicts that genetic diversity increases with population size, yet observed levels of diversity across metazoans vary only two orders of magnitude while population sizes vary over several. This unexpectedly narrow range of diversity is known as Lewontin’s Paradox of Variation (1974). While some have suggested selection constrains diversity, tests of this hypothesis seem to fall short. Here, I revisit Lewontin’s Paradox to assess whether current models of linked selection are capable of reducing diversity to this extent. To quantify the discrepancy between pairwise diversity and census population sizes across species, I combine previously-published estimates of pairwise diversity from 172 metazoan taxa with newly derived estimates of census sizes. Using phylogenetic comparative methods, I show this relationship is significant accounting for phylogeny, but with high phylogenetic signal and evidence that some lineages experience shifts in the evolutionary rate of diversity deep in the past. Additionally, I find a negative relationship between recombination map length and census size, suggesting abundant species have less recombination and experience greater reductions in diversity due to linked selection. However, I show that even assuming strong and abundant selection, models of linked selection are unlikely to explain the observed relationship between diversity and census sizes across species.

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

10.1101/2021.06.11.448122 ◽

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.

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