scholarly journals The Recombinational Landscape in Daphnia pulex

2020 ◽  
Author(s):  
Michael Lynch ◽  
Zhiqiang Ye ◽  
Takahiro Maruki
Keyword(s):  
Linkage Disequilibrium ◽  
Natural Populations ◽  
Daphnia Pulex ◽  
Physical Distance ◽  
Sequencing Data ◽  
Recombination Hotspots ◽  
Genome Wide ◽  
Nucleotide Mutation ◽  
Suppressed Recombination ◽  
The Relationship

AbstractThrough the analysis of linkage disequilibrium from genome-wide sequencing data for multiple individuals from eight populations, the general features of the recombinational landscape are revealed in the microcrustacean Daphnia pulex. The data suggest an exceptionally uniform pattern of recombination across the genome, while also confirming general patterns that are inconsistent with existing population-genetic models for the relationship between linkage dis-equilibrium and physical distances between genomic sites. Patterns of linkage disequilibrium are highly consistent among populations, and average rates of recombination are quite similar for all chromosomes. There is no evidence of recombination hotspots, and although there does appear to be suppressed recombination in the vicinity of gene bodies, this effect is quite small. Although this species reproduces asexually in ∼ 80% of generations, the mean per-generation recombination rate per nucleotide site is ∼ 37× the per-nucleotide mutation rate. Contrary to expectations for models in which crossing-over is the primary mechanism of recombination, and consistent with data for other species, the gradient of linkage disequilibrium with increasing physical distance between sites is far too high at short distances and far too low at long distances, suggesting an important role for factors such as the nonindependent appearance of pairs of mutations on haplotypes and long-range gene-conversion-like processes. Combined with other observations on patterns of nucleotide variation, these results provide a strong case for the utility of D. pulex as a model system for the study of mechanisms of evolution in natural populations.

scholarly journals Negative linkage disequilibrium between amino acid changing variants reveals interference among deleterious mutations in the human genome

PLoS Genetics ◽  
2021 ◽  
Vol 17 (7) ◽  
pp. e1009676
Author(s):  
Jesse A. Garcia ◽  
Kirk E. Lohmueller
Keyword(s):  
Linkage Disequilibrium ◽  
Human Genome ◽  
Natural Populations ◽  
Physical Distance ◽  
Deleterious Mutations ◽  
High Coverage ◽  
Evolutionary Forces ◽  
Recessive Mutations ◽  
Genome Wide ◽  
Negative Epistasis

Evolutionary forces like Hill-Robertson interference and negative epistasis can lead to deleterious mutations being found on distinct haplotypes. However, the extent to which these forces depend on the selection and dominance coefficients of deleterious mutations and shape genome-wide patterns of linkage disequilibrium (LD) in natural populations with complex demographic histories has not been tested. In this study, we first used forward-in-time simulations to predict how negative selection impacts LD. Under models where deleterious mutations have additive effects on fitness, deleterious variants less than 10 kb apart tend to be carried on different haplotypes relative to pairs of synonymous SNPs. In contrast, for recessive mutations, there is no consistent ordering of how selection coefficients affect LD decay, due to the complex interplay of different evolutionary effects. We then examined empirical data of modern humans from the 1000 Genomes Project. LD between derived alleles at nonsynonymous SNPs is lower compared to pairs of derived synonymous variants, suggesting that nonsynonymous derived alleles tend to occur on different haplotypes more than synonymous variants. This result holds when controlling for potential confounding factors by matching SNPs for frequency in the sample (allele count), physical distance, magnitude of background selection, and genetic distance between pairs of variants. Lastly, we introduce a new statistic HR(j) which allows us to detect interference using unphased genotypes. Application of this approach to high-coverage human genome sequences confirms our finding that nonsynonymous derived alleles tend to be located on different haplotypes more often than are synonymous derived alleles. Our findings suggest that interference may play a pervasive role in shaping patterns of LD between deleterious variants in the human genome, and consequently influences genome-wide patterns of LD.

scholarly journals Negative linkage disequilibrium between amino acid changing variants reveals interference among deleterious mutations in the human genome

2020 ◽  
Author(s):  
Jesse A. Garcia ◽  
Kirk E. Lohmueller
Keyword(s):  
Linkage Disequilibrium ◽  
Human Genome ◽  
Natural Populations ◽  
Physical Distance ◽  
Deleterious Mutations ◽  
High Coverage ◽  
Recessive Mutations ◽  
Deleterious Alleles ◽  
Genome Wide ◽  
Negative Epistasis

AbstractWhile there has been extensive work on patterns of linkage disequilibrium (LD) for neutral loci, the extent to which negative selection impacts LD is less clear. Forces like Hill-Robertson interference and negative epistasis are expected to lead to deleterious mutations being found on distinct haplotypes. However, the extent to which these forces depend on the selection and dominance coefficients of deleterious mutations and shape genome-wide patterns of LD in natural populations with complex demographic histories has not been tested. In this study, we first used forward-in-time simulations to generate predictions as to how selection impacts LD. Under models where deleterious mutations have additive effects on fitness, deleterious variants less than 10 kb apart tend to be carried on different haplotypes, generating an excess of negative LD relative to pairs of synonymous SNPs. In contrast, for recessive mutations, there is no consistent ordering of how selection coefficients affect r2 decay. We then examined empirical data of modern humans from the 1000 Genomes Project. LD between derived nonsynonymous SNPs is more negative compared to pairs of derived synonymous variants. This result holds when matching SNPs for frequency in the sample (allele count), physical distance, magnitude of background selection, and genetic distance between pairs of variants, suggesting that this result is not due to these potential confounding factors. Lastly, we introduce a new statistic HR(j) which allows us to detect interference using unphased genotypes. Application of this approach to high-coverage human genome sequences confirms our finding that deleterious alleles tend to be located on different haplotypes more often than are neutral alleles. Our findings suggest that either interference or negative epistasis plays a pervasive role in shaping patterns of LD between deleterious variants in the human genome, and consequently influencing genome-wide patterns of LD.

scholarly journals Complex and long-range linkage disequilibrium and its relationship with QTL for Marek's Disease resistance in chicken populations

2021 ◽  
Author(s):  
Ehud Lipkin
Keyword(s):  
Linkage Disequilibrium ◽  
Long Range ◽  
Snp Array ◽  
Causative Mutation ◽  
Significant Marker ◽  
Genome Wide ◽  
Random Samples ◽  
Block Complexity ◽  
String Networks ◽  
The Relationship

Chicken long-range linkage disequilibrium (LRLD) and LD blocks, and their relationship with previously described Mareks Disease (MD) quantitative trait loci regions (QTLRs), were studied in an F6 population from a full-sib advanced intercross line (FSAIL), and in eight commercial pure layer lines. Genome wide LRLD was studied in the F6 population by random samples of non-syntenic and syntenic marker pairs genotyped by Affymetrix HD 600K SNP array. To illustrate the relationship with QTLRs, LRLD and LD blocks in and between the MD QTLRs were studied by all possible marker pairs of all array markers in the QTLRs, using the same F6 QTLR genotypes and genotypes of the QTLR elements' markers in the eight lines used in the MD mapping study. LRLD was defined as r2 ≥ 0.7 over a distance ≥ 1 Mb, and 1.5% of all syntenic marker pairs were classified as LRLD. Complex fragmented and interdigitated LD blocks were found, over distances ranging from a few hundred to a few million bases. Vast high, long-range, and complex LD was found between two of the MD QTLRs. Cross QTLRs STRING networks and gene interactions suggested possible origins of this exceptional QTLRs' LD. Thus, causative mutations can be located at a much larger distance from a significant marker than previously appreciated. LRLD range and LD block complexity may be used to identify mapping errors, and should be accounted for while interpreting genetic mapping studies. All sites with high LD with a significant marker should be considered as candidate for the causative mutation.

scholarly journals Pervasive Linked Selection and Intermediate-Frequency Alleles Are Implicated in an Evolve-and-Resequencing Experiment of Drosophila simulans

Genetics ◽  
2018 ◽  
Vol 211 (3) ◽  
pp. 943-961 ◽  
Author(s):  
John K. Kelly ◽  
Kimberly A. Hughes
Keyword(s):  
Balancing Selection ◽  
Parallel Evolution ◽  
Rapid Evolution ◽  
Natural Populations ◽  
Intermediate Frequency ◽  
Drosophila Simulans ◽  
Data Sets ◽  
Sequencing Data ◽  
Simulation Tools ◽  
Genome Wide

We develop analytical and simulation tools for evolve-and-resequencing experiments and apply them to a new study of rapid evolution in Drosophila simulans. Likelihood test statistics applied to pooled population sequencing data suggest parallel evolution of 138 SNPs across the genome. This number is reduced by orders of magnitude from previous studies (thousands or tens of thousands), owing to differences in both experimental design and statistical analysis. Whole genome simulations calibrated from Drosophila genetic data sets indicate that major features of the genome-wide response could be explained by as few as 30 loci under strong directional selection with a corresponding hitchhiking effect. Smaller effect loci are likely also responding, but are below the detection limit of the experiment. Finally, SNPs showing strong parallel evolution in the experiment are intermediate in frequency in the natural population (usually 30–70%) indicative of balancing selection in nature. These loci also exhibit elevated differentiation among natural populations of D. simulans, suggesting environmental heterogeneity as a potential balancing mechanism.

scholarly journals On the genetic architecture of rapidly adapting and convergent life history traits in guppies

2021 ◽  
Author(s):  
James R Whiting ◽  
Josephine R Paris ◽  
Paul J Parsons ◽  
Sophie Matthews ◽  
Yuridia Reynoso ◽  
...  
Keyword(s):  
Life History ◽  
Life Histories ◽  
Genetic Architecture ◽  
Genetic Basis ◽  
Natural Populations ◽  
Female Size ◽  
Size At Maturity ◽  
Sequencing Data ◽  
Genome Wide ◽  
Polygenic Traits

The genetic basis of traits can shape and constrain how adaptation proceeds in nature; rapid adaptation can be facilitated by polygenic traits, whereas polygenic traits may restrict re-use of the same genes in adaptation (genetic convergence). The rapidly evolving life histories of guppies in response to predation risk provide an opportunity to test this proposition. Guppies adapted to high- (HP) and low-predation (LP) environments in northern Trinidad evolve rapidly and convergently among natural populations. This system has been studied extensively at the phenotypic level, but little is known about the underlying genetic architecture. Here, we use an F2 QTL design to examine the genetic basis of seven (five female, two male) guppy life history phenotypes. We use RAD-sequencing data (16,539 SNPs) from 370 male and 267 female F2 individuals. We perform linkage mapping, estimates of genome-wide and per-chromosome heritability (multi-locus associations), and QTL mapping (single-locus associations). Our results are consistent with architectures of many-loci of small effect for male age and size at maturity and female interbrood period. Male trait associations are clustered on specific chromosomes, but female interbrood period exhibits a weak genome-wide signal suggesting a potentially highly polygenic component. Offspring weight and female size at maturity are also associated with a single significant QTL each. These results suggest rapid phenotypic evolution of guppies may be facilitated by polygenic trait architectures, but these may restrict gene-reuse across populations, in agreement with an absence of strong signatures of genetic convergence from recent population genomic analyses of wild HP-LP guppies.

scholarly journals On the relationship between high-order linkage disequilibrium and epistasis

2018 ◽  
Author(s):  
Yanjun Zan ◽  
Simon K. G. Forsberg ◽  
Örjan Carlborg
Keyword(s):  
Linkage Disequilibrium ◽  
Genetic Architecture ◽  
Genomic Region ◽  
High Order ◽  
Common Assumption ◽  
Association Analyses ◽  
Functional Polymorphisms ◽  
Genome Wide ◽  
The Common ◽  
The Relationship

AbstractA plausible explanation for statistical epistasis revealed in genome wide association analyses is the presence of high order linkage disequilibrium (LD) between the genotyped markers tested for interactions and unobserved functional polymorphisms. Based on findings in experimental data, it has been suggested that high order LD might be a common explanation for statistical epistasis inferred between local polymorphisms in the same genomic region. Here, we empirically evaluate how prevalent high order LD is between local, as well as distal, polymorphisms in the genome. This could provide insights into whether we should account for this when interpreting results from genome wide scans for statistical epistasis. An extensive and strong genome wide high order LD was revealed between pairs of markers on the high density 250k SNP-chip and individual markers revealed by whole genome sequencing in the A. thaliana 1001-genomes collection. The high order LD was found to be more prevalent in smaller populations, but present also in samples including several hundred individuals. An empirical example illustrates that high order LD might be an even greater challenge in cases when the genetic architecture is more complex than the common assumption of bi-allelic loci. The example shows how significant statistical epistasis is detected for a pair of markers in high order LD with a complex multi allelic locus. Overall, our study illustrates the importance of considering also other explanations than functional genetic interactions when genome wide statistical epistasis is detected, in particular when the results are obtained in small populations of inbred individuals.

scholarly journals Unbiased Estimation of Linkage Disequilibrium from Unphased Data

2019 ◽  
Vol 37 (3) ◽  
pp. 923-932 ◽  
Author(s):  
Aaron P Ragsdale ◽  
Simon Gravel
Keyword(s):  
Linkage Disequilibrium ◽  
Unbiased Estimation ◽  
Sequencing Data ◽  
Effective Population ◽  
Island Fox ◽  
Wide Range ◽  
Population Sizes ◽  
The Common ◽  
Genomic Regions ◽  
The Relationship

Abstract Linkage disequilibrium (LD) is used to infer evolutionary history, to identify genomic regions under selection, and to dissect the relationship between genotype and phenotype. In each case, we require accurate estimates of LD statistics from sequencing data. Unphased data present a challenge because multilocus haplotypes cannot be inferred exactly. Widely used estimators for the common statistics r2 and D2 exhibit large and variable upward biases that complicate interpretation and comparison across cohorts. Here, we show how to find unbiased estimators for a wide range of two-locus statistics, including D2, for both single and multiple randomly mating populations. These unbiased statistics are particularly well suited to estimate effective population sizes from unlinked loci in small populations. We develop a simple inference pipeline and use it to refine estimates of recent effective population sizes of the threatened Channel Island Fox populations.

scholarly journals ngsLD: evaluating linkage disequilibrium using genotype likelihoods

2019 ◽  
Vol 35 (19) ◽  
pp. 3855-3856 ◽  
Author(s):  
Emma A Fox ◽  
Alison E Wright ◽  
Matteo Fumagalli ◽  
Filipe G Vieira
Keyword(s):  
Linkage Disequilibrium ◽  
Large Scale ◽  
Read Depth ◽  
Physical Distance ◽  
Data Uncertainty ◽  
Supplementary Information ◽  
Model Organisms ◽  
Sequencing Data ◽  
Sequencing Strategy ◽  
User Friendly

Abstract Motivation Linkage disequilibrium (LD) measures the correlation between genetic loci and is highly informative for association mapping and population genetics. As many studies rely on called genotypes for estimating LD, their results can be affected by data uncertainty, especially when employing a low read depth sequencing strategy. Furthermore, there is a manifest lack of tools for the analysis of large-scale, low-depth and short-read sequencing data from non-model organisms with limited sample sizes. Results ngsLD addresses these issues by estimating LD directly from genotype likelihoods in a fast, reliable and user-friendly implementation. This method makes use of the full information available from sequencing data and provides accurate estimates of linkage disequilibrium patterns compared with approaches based on genotype calling. We conducted a case study to investigate how LD decays over physical distance in two avian species. Availability and implementation The methods presented in this work were implemented in C/C and are freely available for non-commercial use from https://github.com/fgvieira/ngsLD. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Partial sex linkage and linkage disequilibrium on the guppy sex chromosome

2022 ◽  
Author(s):  
Suo Qiu ◽  
Lenxob Yong ◽  
Alstair Wilson ◽  
Darrren P Croft ◽  
Chay Graham ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Sex Chromosome ◽  
Natural Populations ◽  
Sex Linkage ◽  
Recombination Suppression ◽  
Genome Region ◽  
A Genome ◽  
Suppressed Recombination ◽  
Male Specific ◽  
New Evidence

The guppy Y chromosome has been considered a model system for the evolution of suppressed recombination between sex chromosomes, and it has been proposed that complete sex-linkage has evolved across about 3 Mb surrounding the sex-determining locus of this fish, followed by recombination suppression across a further 7 Mb of the 23 Mb XY pair, forming younger evolutionary strata. Sequences of the guppy genome show that Y is very similar to the X chromosome, making it important to understand which parts of the Y are completely non-recombining, and whether there is indeed a large completely non-recombining region. Here, we describe new evidence that supports a different interpretation of the data that suggested the presence of such a region. We analysed PoolSeq data in samples from multiple natural populations from Trinidad. This yields evidence for linkage disequilibrium (LD) between sequence variants and the sex-determining locus. Downstream populations have higher diversity than upstream ones (which display the expected signs of bottlenecks). The associations we observe conform to predictions for a genome region with infrequent recombination that carries one or more sexually antagonistic polymorphisms. They also suggest the region in which the sex-determining locus must be located. However, no consistently male-specific variants were found, supporting the suggestion that any completely sex-linked region may be very small.

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