scholarly journals Impact of Mutation Rate and Selection at Linked Sites on DNA Variation across the Genomes of Humans and Other Homininae

2019 ◽  
Vol 12 (1) ◽  
pp. 3550-3561 ◽  
Author(s):  
David Castellano ◽  
Adam Eyre-Walker ◽  
Kasper Munch
Keyword(s):  
Mutation Rate ◽  
Recombination Rate ◽  
Regional Variation ◽  
Rate Variation ◽  
Species Variation ◽  
Effective Population ◽  
Conserved Sequences ◽  
Positive Correlation ◽  
Dna Diversity ◽  
A Genome

Abstract DNA diversity varies across the genome of many species. Variation in diversity across a genome might arise from regional variation in the mutation rate, variation in the intensity and mode of natural selection, and regional variation in the recombination rate. We show that both noncoding and nonsynonymous diversity are positively correlated to a measure of the mutation rate and the recombination rate and negatively correlated to the density of conserved sequences in 50 kb windows across the genomes of humans and nonhuman homininae. Interestingly, we find that although noncoding diversity is equally affected by these three genomic variables, nonsynonymous diversity is mostly dominated by the density of conserved sequences. The positive correlation between diversity and our measure of the mutation rate seems to be largely a direct consequence of regions with higher mutation rates having more diversity. However, the positive correlation with recombination rate and the negative correlation with the density of conserved sequences suggest that selection at linked sites also affect levels of diversity. This is supported by the observation that the ratio of the number of nonsynonymous to noncoding polymorphisms is negatively correlated to a measure of the effective population size across the genome. We show these patterns persist even when we restrict our analysis to GC-conservative mutations, demonstrating that the patterns are not driven by GC biased gene conversion. In conclusion, our comparative analyses describe how recombination rate, gene density, and mutation rate interact to produce the patterns of DNA diversity that we observe along the hominine genomes.

scholarly journals Impact of mutation rate and selection at linked sites on fine-scale DNA variation across the homininae genome

2018 ◽  
Author(s):  
David Castellano ◽  
Adam Eyre-Walker ◽  
Kasper Munch
Keyword(s):  
Gene Conversion ◽  
Mutation Rate ◽  
Genetic Drift ◽  
Recombination Rate ◽  
Small Populations ◽  
Conserved Sequences ◽  
Positive Correlation ◽  
Dna Diversity ◽  
Biased Gene Conversion ◽  
The Impact

AbstractDNA diversity varies across the genome of many species. Variation in diversity across a genome might arise for one of three reasons; regional variation in the mutation rate, selection and biased gene conversion. We show that both non-coding and non-synonymous diversity are correlated to a measure of the mutation rate, the recombination rate and the density of conserved sequences in 50KB windows across the genomes of humans and non-human homininae. We show these patterns persist even when we restrict our analysis to GC-conservative mutations, demonstrating that the patterns are not driven by biased gene conversion. The positive correlation between diversity and our measure of the mutation rate seems to be largely a direct consequence of regions with higher mutation rates having more diversity. However, the positive correlation with recombination rate and the negative correlation with the density of conserved sequences suggests that selection at linked sites affect levels of diversity. This is supported by the observation that the ratio of the number of non-synonymous to non-coding polymorphisms is negatively correlated to a measure of the effective population size across the genome. Furthermore, we find evidence that these genomic variables are better predictors of non-coding diversity in large homininae populations than in small populations, after accounting for statistical power. This is consistent with genetic drift decreasing the impact of selection at linked sites in small populations. In conclusion, our comparative analyses describe for the first time how recombination rate, gene density, mutation rate and genetic drift interact to produce the patterns of DNA diversity that we observe along and between homininae genomes.

scholarly journals Detecting recent selective sweeps while controlling for mutation rate and background selection

2015 ◽  
Author(s):  
Christian D. Huber ◽  
Michael DeGiorgio ◽  
Ines Hellmann ◽  
Rasmus Nielsen
Keyword(s):  
Spatial Pattern ◽  
Mutation Rate ◽  
Composite Likelihood ◽  
Causative Mutation ◽  
Rate Variation ◽  
Ratio Test ◽  
Background Selection ◽  
Selective Sweeps ◽  
Effective Population ◽  
A Genome

A composite likelihood ratio test implemented in the program SweepFinder is a commonly used method for scanning a genome for recent selective sweeps. SweepFinder uses information on the spatial pattern of the site frequency spectrum (SFS) around the selected locus. To avoid confounding effects of background selection and variation in the mutation process along the genome, the method is typically applied only to sites that are variable within species. However, the power to detect and localize selective sweeps can be greatly improved if invariable sites are also included in the analysis. In the spirit of a Hudson-Kreitman-Aguadé test, we suggest to add fixed differences relative to an outgroup to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection modeled as a local reduction in the effective population size. Using simulations we show that these advances lead to a gain in power while maintaining robustness to mutation rate variation. Furthermore, the new method also provides more precise localization of the causative mutation than methods using the spatial pattern of segregating sites alone.

scholarly journals Mutation rate analysis via parent–progeny sequencing of the perennial peach. II. No evidence for recombination-associated mutation

2016 ◽  
Vol 283 (1841) ◽  
pp. 20161785 ◽  
Author(s):  
Long Wang ◽  
Yanchun Zhang ◽  
Chao Qin ◽  
Dacheng Tian ◽  
Sihai Yang ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Recombination Rate ◽  
Mutation Rates ◽  
Recombination Rates ◽  
Rate Analysis ◽  
A Genome ◽  
Break Points ◽  
New Mutations

Mutation rates and recombination rates vary between species and between regions within a genome. What are the determinants of these forms of variation? Prior evidence has suggested that the recombination might be mutagenic with an excess of new mutations in the vicinity of recombination break points. As it is conjectured that domesticated taxa have higher recombination rates than wild ones, we expect domesticated taxa to have raised mutation rates. Here, we use parent–offspring sequencing in domesticated and wild peach to ask (i) whether recombination is mutagenic, and (ii) whether domesticated peach has a higher recombination rate than wild peach. We find no evidence that domesticated peach has an increased recombination rate, nor an increased mutation rate near recombination events. If recombination is mutagenic in this taxa, the effect is too weak to be detected by our analysis. While an absence of recombination-associated mutation might explain an absence of a recombination–heterozygozity correlation in peach, we caution against such an interpretation.

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

2018 ◽  
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.

scholarly journals The Amount of DNA Polymorphism Maintained in a Finite Population When the Neutral Mutation Rate Varies Among Sites

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1457-1465 ◽  
Author(s):  
Fumio Tajima
Keyword(s):  
Mutation Rate ◽  
Finite Population ◽  
Rate Variation ◽  
Effective Population ◽  
Site Model ◽  
New Methods ◽  
Infinite Site Model ◽  
Minimum Number ◽  
Input Model ◽  
Neutral Mutation Rate

Abstract The expectations of the average number of nucleotide differences per site (π), the proportion of segregating site (s), the minimum number of mutations per site (s*) and some other quantities were derived under the finite site models with and without rate variation among sites, where the finite site models include Jukes and Cantor's model, the equal-input model and Kimura's model. As a model of rate variation, the gamma distribution was used. The results indicate that if distribution parameter α is small, the effect of rate variation on these quantities are substantial, so that the estimates of θ based on the infinite site model are substantially underestimated, where θ = 4Nv, N is the effective population size and vis the mutation rate per site per generation. New methods for estimating θ are also presented, which are based on the finite site models with and without rate variation. Using these methods, underestimation can be corrected.

scholarly journals Genetics of recombination rate variation in the pig

2020 ◽  
Author(s):  
Martin Johnsson ◽  
Andrew Whalen ◽  
Roger Ros-Freixedes ◽  
Gregor Gorjanc ◽  
Ching-Yi Chen ◽  
...  
Keyword(s):  
Recombination Rate ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Chromosome Length ◽  
Rate Variation ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions ◽  
Iterative Peeling ◽  
Recombination Rate Variation

AbstractBackgroundIn this paper, we estimated recombination rate variation within the genome and between individuals in the pig using multiocus iterative peeling for 150,000 pigs across nine genotyped pedigrees. We used this to estimate the heritability of recombination and perform a genome-wide association study of recombination in the pig.ResultsOur results confirmed known features of the pig recombination landscape, including differences in chromosome length, and marked sex differences. The recombination landscape was repeatable between lines, but at the same time, the lines also showed differences in average genome-wide recombination rate. The heritability of genome-wide recombination was low but non-zero (on average 0.07 for females and 0.05 for males). We found three genomic regions associated with recombination rate, one of them harbouring the RNF212 gene, previously associated with recombination rate in several other species.ConclusionOur results from the pig agree with the picture of recombination rate variation in vertebrates, with low but nonzero heritability, and a major locus that is homologous to one detected in several other species. This work also highlights the utility of using large-scale livestock data to understand biological processes.

scholarly journals A genome-wide study of recombination rate variation in Bartonella henselae

2012 ◽  
Vol 12 (1) ◽  
pp. 65 ◽  
Author(s):  
Lionel Guy ◽  
Björn Nystedt ◽  
Yu Sun ◽  
Kristina Näslund ◽  
Eva C Berglund ◽  
...  
Keyword(s):  
Recombination Rate ◽  
Bartonella Henselae ◽  
Rate Variation ◽  
Genome Wide ◽  
A Genome ◽  
Recombination Rate Variation ◽  
Genome Wide Study

scholarly journals Recombination Rate Variation and Infrequent Sex Influence Genetic Diversity in Chlamydomonas reinhardtii

2020 ◽  
Vol 12 (4) ◽  
pp. 370-380 ◽  
Author(s):  
Ahmed R Hasan ◽  
Rob W Ness
Keyword(s):  
Linkage Disequilibrium ◽  
Chlamydomonas Reinhardtii ◽  
Recombination Rate ◽  
Natural Populations ◽  
Effective Rate ◽  
Sexual Cycle ◽  
Rate Variation ◽  
Effective Population ◽  
Recombination Rates ◽  
Recombination Rate Variation

Abstract Recombination confers a major evolutionary advantage by breaking up linkage disequilibrium between harmful and beneficial mutations, thereby facilitating selection. However, in species that are only periodically sexual, such as many microbial eukaryotes, the realized rate of recombination is also affected by the frequency of sex, meaning that infrequent sex can increase the effects of selection at linked sites despite high recombination rates. Despite this, the rate of sex of most facultatively sexual species is unknown. Here, we use genomewide patterns of linkage disequilibrium to infer fine-scale recombination rate variation in the genome of the facultatively sexual green alga Chlamydomonas reinhardtii. We observe recombination rate variation of up to two orders of magnitude and find evidence of recombination hotspots across the genome. Recombination rate is highest flanking genes, consistent with trends observed in other nonmammalian organisms, though intergenic recombination rates vary by intergenic tract length. We also find a positive relationship between nucleotide diversity and physical recombination rate, suggesting a widespread influence of selection at linked sites in the genome. Finally, we use estimates of the effective rate of recombination to calculate the rate of sex that occurs in natural populations, estimating a sexual cycle roughly every 840 generations. We argue that the relatively infrequent rate of sex and large effective population size creates a population genetic environment that increases the influence of selection on linked sites across the genome.

scholarly journals Variation of the adaptive substitution rate between species and within genomes

2019 ◽  
Vol 34 (3) ◽  
pp. 315-338 ◽  
Author(s):  
Ana Filipa Moutinho ◽  
Thomas Bataillon ◽  
Julien Y. Dutheil
Keyword(s):  
Molecular Evolution ◽  
Population Genomics ◽  
Species Variation ◽  
Effective Population ◽  
Adaptive Mutations ◽  
A Genome ◽  
Main Driver ◽  
Recent Developments ◽  
Wide Scale ◽  
Adaptive Substitution

AbstractThe importance of adaptive mutations in molecular evolution is extensively debated. Recent developments in population genomics allow inferring rates of adaptive mutations by fitting a distribution of fitness effects to the observed patterns of polymorphism and divergence at sites under selection and sites assumed to evolve neutrally. Here, we summarize the current state-of-the-art of these methods and review the factors that affect the molecular rate of adaptation. Several studies have reported extensive cross-species variation in the proportion of adaptive amino-acid substitutions (α) and predicted that species with larger effective population sizes undergo less genetic drift and higher rates of adaptation. Disentangling the rates of positive and negative selection, however, revealed that mutations with deleterious effects are the main driver of this population size effect and that adaptive substitution rates vary comparatively little across species. Conversely, rates of adaptive substitution have been documented to vary substantially within genomes. On a genome-wide scale, gene density, recombination and mutation rate were observed to play a role in shaping molecular rates of adaptation, as predicted under models of linked selection. At the gene level, it has been reported that the gene functional category and the macromolecular structure substantially impact the rate of adaptive mutations. Here, we deliver a comprehensive review of methods used to infer the molecular adaptive rate, the potential drivers of adaptive evolution and how positive selection shapes molecular evolution within genes, across genes within species and between species.

A Coalescent Estimator of the Population Recombination Rate

Genetics ◽  
1997 ◽  
Vol 145 (3) ◽  
pp. 833-846 ◽  
Author(s):  
Jody Hey ◽  
John Wakeley
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
Mutation Rate ◽  
Dna Sequences ◽  
Recombination Rate ◽  
Population Sample ◽  
Population Level ◽  
Effective Population ◽  
Genome Level ◽  
Population Recombination

Population genetic models often use a population recombination parameter 4Nc, where N is the effective population size and c is the recombination rate per generation. In many ways 4Nc is comparable to 4Nu, the population mutation rate. Both combine genome level and population level processes, and together they describe the rate of production of genetic variation in a population. However, 4Nc is more difficult to estimate. For a population sample of DNA sequences, historical recombination can only be detected if polymorphisms exist, and even then most recombination events are not detectable. This paper describes an estimator of 4Nc, hereafter designated γ (gamma), that was developed using a coalescent model for a sample of four DNA sequences with recombination. The reliability of γ was assessed using multiple coalescent simulations. In general γ has low to moderate bias, and the reliability of γ is comparable, though less, than that for a widely used estimator of 4Nu. If there exists an independent estimate of the recombination rate (per generation, per base pair), γ can be used to estimate the effective population size or the neutral mutation rate.

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