scholarly journals Genetic load may increase or decrease with selfing depending upon the recombination environment

2021 ◽  
Author(s):  
Shelley A Sianta ◽  
Stephan Peischl ◽  
David A Moeller ◽  
Yaniv Brandvain
Keyword(s):  
Balancing Selection ◽  
Random Mating ◽  
Genetic Load ◽  
Threshold Level ◽  
Mutation Rates ◽  
Selfing Rate ◽  
Effective Population ◽  
Recombination Rates ◽  
Genomic Changes ◽  
Recessive Mutations

Theory predicts that the ability for natural selection to remove deleterious mutations from a population, and prevent the accumulation of genetic load, is a function of the effective population size (Ne). Shifts from random mating to self-fertilization (selfing) are predicted to decrease Ne through a variety of genomic changes - including a reduction in effective recombination and an increase in homozygosity. While a long history of theory suggests that the efficacy of selection, particularly against non-recessive mutations, should decrease with selfing rate, comparisons of genomic-based estimates of the efficacy of selection between related outcrosser-selfer pairs have revealed conflicting results. We address this paradox by simulating the evolution of strongly deleterious recessive and weakly deleterious additive mutations across a range of recombination, mutation and selective parameter combinations. We find that the genetic load of a population can either increase, decrease, or not vary with selfing rate. Genetic load is higher in selfers only when recombination rates are greater than mutation rates. When recombination rates are lower than mutation rates, an accumulation of recessive mutations leads to pseudo-overdominance, a type of balancing selection, in outcrossing populations. Using both simulations and analytical theory, we show that pseudo-overdominance has strong negative effects on the efficacy of selection against linked additive mutations and that a threshold level of selfing prevents pseudo-overdominance. Our results show that selection can be more or less effective in selfers as compared to outcrossers depending on the relationship between the deleterious mutation rate and gene density, and therefore different genomic regions in different taxa could show differing results.

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 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 Inbreeding depression and genetic load at partially linked loci in a metapopulation

2010 ◽  
Vol 92 (2) ◽  
pp. 127-140 ◽  
Author(s):  
SHU-RONG ZHOU ◽  
JOHN R. PANNELL
Keyword(s):  
Inbreeding Depression ◽  
Random Mating ◽  
Genetic Load ◽  
Minor Effect ◽  
Deleterious Mutations ◽  
Recombination Rates ◽  
Sexual Systems ◽  
Biological Phenomena ◽  
Population Turnover ◽  
Wide Range

SummaryInbreeding depression has important implications for a wide range of biological phenomena, such as inbreeding avoidance, the evolution and maintenance of sexual systems and extinction rates of small populations. Previous investigations have asked how inbreeding depression evolves in single and subdivided populations through the fixation of deleterious mutations as a result of drift, as well as through the expression of deleterious mutations segregating in a population. These studies have focused on the effects of mutation and selection at single loci, or at unlinked loci. Here, we used simulations to investigate the evolution of genetic load and inbreeding depression due to multiple partially linked loci in metapopulations. Our results indicate that the effect of linkage depends largely on the kinds of deleterious alleles involved. For weakly deleterious and partially recessive mutations, the speed of mutation accumulation at segregating loci in a random-mating subdivided population of a given structure tends to be retarded by increased recombination between adjacent loci – although the highest numbers of fixation of slightly recessive mutant alleles were for low but finite recombination rates. Although linkage had a relatively minor effect on the evolution of metapopulations unless very low values of recombination were assumed, close linkage between adjacent loci tended to enhance population structure and population turnover. Finally, within-deme inbreeding depression, between-deme inbreeding depression and heterosis generally increased with decreased recombination rates. Moreover, increased selfing reduced the effective amount of recombination, and hence the effects of tight linkage on metapopulation genetic structure were decreased with increasing selfing. In contrast, linkage had little effect on the fate of lethal and highly recessive alleles. We compare our simulation results with predictions made by models that ignore the complexities of recombination.

scholarly journals Mating system and recombination affect molecular evolution in four Triticeae species

2008 ◽  
Vol 90 (1) ◽  
pp. 97-109 ◽  
Author(s):  
A. HAUDRY ◽  
A. CENCI ◽  
C. GUILHAUMON ◽  
E. PAUX ◽  
S. POIRIER ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Mating System ◽  
Mating Systems ◽  
Genetic Load ◽  
Gc Content ◽  
Aegilops Speltoides ◽  
Effective Population ◽  
Recombination Rates ◽  
Biased Gene Conversion ◽  
Evolution Of Genomes

SummaryMating systems and recombination are thought to have a deep impact on the organization and evolution of genomes. Because of the decline in effective population size and the interference between linked loci, the efficacy of selection is expected to be reduced in regions with low recombination rates and in the whole genome of self-fertilizing species. At the molecular level, relaxed selection is expected to result in changes in the rate of protein evolution and the pattern of codon bias. It is increasingly recognized that recombination also affects non-selective processes such as the biased gene conversion towards GC alleles (bGC). Like selection, this kind of meiotic drive in favour of GC over AT alleles is expected to be reduced in weakly recombining regions and genomes. Here, we investigated the effect of mating system and recombination on molecular evolution in four Triticeae species: two outcrossers (Secale cereale and Aegilops speltoides) and two selfers (Triticum urartu and Triticum monococcum). We found that GC content, possibly driven by bGC, is affected by mating system and recombination as theoretically predicted. Selection efficacy, however, is only weakly affected by mating system and recombination. We investigated the possible reasons for this discrepancy. A surprising one is that, in outcrossing lineages, selection efficacy could be reduced because of high substitution rates in favour of GC alleles. Outcrossers, but not selfers, would thus suffer from a ‘GC-induced’ genetic load. This result sheds new light on the evolution of mating systems.

scholarly journals Joint estimation of selection intensity and mutation rate under balancing selection withapplications to HLA

2021 ◽  
Author(s):  
Montgomery Slatkin
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
Balancing Selection ◽  
Composite Likelihood ◽  
Joint Estimation ◽  
Likelihood Method ◽  
Mutation Rates ◽  
Symmetric Model ◽  
Effective Population ◽  
Selection Intensities

A composite likelihood method is introduced for jointly estimating the intensity of selection and the rate of mutation, both scaled by the effective population size, when there is balancing selection at a single multi-allelic locus in an isolated population at demographic equilibrium. The performance of the method is tested using simulated data. Average estimated mutation rates and selection intensities are close to the true values but there is considerable variation about the averages. Allowing for both population growth and population subdivision do not result in qualitative differences but the estimated mutation rates and selection intensities do not in general reflect the current effective population size. The method is applied to three class I (HLA-A, HLA-B and HLA-C) and two class II loci (HLA-DRB1 and HLA-DQA1) in the 1000 Genomes populations. Allowing for asymmetric balancing selection has only a slight effect on the results from the symmetric model. Mutations that restore symmetry of the selection model are preferentially retained because of the tendency of natural selection to maximize average fitness. However, slight differences in selective effects result in much longer persistence time of some alleles. Trans-species polymorphism (TSP), which is characteristic of MHC in vertebrates, is more likely when there are small differences in allelic fitness than when complete symmetry is assumed. Therefore, variation in allelic fitness expands the range of parameter values consistent with observations of TSP.

The Kota of the Nilgiri hills: a demographic study

1976 ◽  
Vol 8 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Aloke Kumar Ghosh
Keyword(s):  
Total Population ◽  
Random Mating ◽  
High Rate ◽  
Moderate Intensity ◽  
Biological Study ◽  
Isolated Population ◽  
Demographic Structure ◽  
Effective Population ◽  
Mating Population ◽  
The Village

A population–biological study of the Kota of the Nilgiri Hills was undertaken between May 1966 and January 1968. This paper discusses the demographic structure of the tribe and its genetic implications.The Kota is a small tribe of 1203 individuals distributed in only seven villages; it is an isolated population with a low rate of fertility and a high rate of infant mortality. The Kota is not a random mating population. The rate of consanguineous marriages is high and the coefficient of inbreeding is almost equal to the highest recorded value. Besides cousin marriages, marriage within the village is very much preferred. The admixture rate (0·29%) among the Kota is very low. The effective population size is only 28·87% of the total population. The coefficient of breeding isolation is 1·01, which indicates that genetic drift may produce important differentiation in this population. The data show that selection is acting with moderate intensity in this population.

Overt and Concealed Genetic Loads Revealed by QTL Mapping of Genotype-dependent Viability in the Pacific Oyster Crassostrea gigas

Genetics ◽  
2021 ◽  
Author(s):  
Xiaoshen Yin ◽  
Dennis Hedgecock
Keyword(s):  
Genetic Diversity ◽  
Crassostrea Gigas ◽  
Pacific Oyster ◽  
Genetic Load ◽  
High Density ◽  
High Genetic Diversity ◽  
High Fecundity ◽  
Recessive Mutations ◽  
Genotype Frequencies ◽  
The Pacific

Abstract Understanding the genetic bases of inbreeding depression, heterosis, and genetic load is integral to understanding how genetic diversity is maintained in natural populations. The Pacific oyster Crassostrea gigas, like many long-lived plants, has high fecundity and high early mortality (type-III survivorship), manifesting a large, overt, genetic load; the oyster harbors an even greater concealed genetic load revealed by inbreeding. Here, we map viability QTL (vQTL) in six interrelated F2 oyster families, using high-density linkage maps of single nucleotide polymorphisms generated by genotyping-by-sequencing (GBS) methods. Altogether, we detect 70 vQTL and provisionally infer 89 causal mutations, 11 to 20 per family. Genetic mortality caused by independent (unlinked) vQTL ranges from 94.2% to 97.8% across families, consistent with previous reports. High-density maps provide better resolution of genetic mechanisms, however. Models of one causal mutation present in both identical-by-descent (IBD) homozygotes and heterozygotes fit genotype frequencies at 37 vQTL; consistent with the mutation-selection balance theory of genetic load, 20 are highly deleterious, completely recessive mutations and 17 are less deleterious, partially dominant mutations. Another 22 vQTL require pairs of recessive or partially dominant causal mutations, half showing selection against recessive mutations linked in repulsion, producing pseudo-overdominance. Only eight vQTL appear to support the overdominance theory of genetic load, with deficiencies of both IBD homozygotes, but at least four of these are likely caused by pseudo-overdominance. Evidence for epistasis is absent. A high mutation rate, random genetic drift, and pseudo-overdominance may explain both the oyster’s extremely high genetic diversity and a high genetic load maintained primarily by mutation-selection balance.

scholarly journals Estimating effective population size from samples of sequences: a bootstrap Monte Carlo integration method

1992 ◽  
Vol 60 (3) ◽  
pp. 209-220 ◽  
Author(s):  
Joseph Felsenstein
Keyword(s):  
Monte Carlo ◽  
Maximum Likelihood ◽  
Population Size ◽  
Effective Population Size ◽  
Random Mating ◽  
Computational Effort ◽  
Monte Carlo Integration ◽  
Bootstrap Sampling ◽  
Effective Population ◽  
Full Data

SummaryWe would like to use maximum likelihood to estimate parameters such as the effective population size Ne, or, if we do not know mutation rates, the product 4Neμof mutation rate per site and effective population size. To compute the likelihood for a sample of unrecombined nucleotide sequences taken from a random-mating population it is necessary to sum over all genealogies that could have led to the sequences, computing for each one the probability that it would have yielded the sequences, and weighting each one by its prior probability. The genealogies vary in tree topology and in branch lengths. Although the likelihood and the prior are straightforward to compute, the summation over all genealogies seems at first sight hopelessly difficult. This paper reports that it is possible to carry out a Monte Carlo integration to evaluate the likelihoods pproximately. The method uses bootstrap sampling of sites to create data sets for each of which a maximum likelihood tree is estimated. The resulting trees are assumed to be sampled from a distribution whose height is proportional to the likelihood surface for the full data. That it will be so is dependent on a theorem which is not proven, but seems likely to be true if the sequences are not short. One can use the resulting estimated likelihood curve to make a maximum likelihood estimate of the parameter of interest, Ne or of 4Neμ. The method requires at least 100 times the computational effort required for estimation of a phylogeny by maximum likelihood, but is practical on today's work stations. The method does not at present have any way of dealing with recombination.

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 IDENTITY COEFFICIENTS IN FINITE POPULATIONS. I. EVOLUTION OF IDENTITY COEFFICIENTS IN A RANDOM MATING DIPLOID DIOECIOUS POPULATION

Genetics ◽  
1977 ◽  
Vol 86 (3) ◽  
pp. 697-713
Author(s):  
C Chevalet ◽  
M Gillois ◽  
R F Nassar
Keyword(s):  
Genetic Variability ◽  
Population Size ◽  
Effective Population Size ◽  
Random Mating ◽  
Matrix Multiplication ◽  
Inbred Lines ◽  
Inbreeding Coefficient ◽  
Effective Population ◽  
The Mean ◽  
Over Time

ABSTRACT Properties of identity relation between genes are discussed, and a derivation of recurrent equations of identity coefficients in a random mating, diploid dioecious population is presented. Computations are run by repeated matrix multiplication. Results show that for effective population size (Ne) larger than 16 and no mutation, a given identity coefficient at any time t can be expressed approximately as a function of (1—f), (1—f)3 and (1—f)6, where f is the mean inbreeding coefficient at time t. Tables are presented, for small Ne values and extreme sex ratios, showing the pattern of change in the identity coefficients over time. The pattern of evolution of identity coefficients is also presented and discussed with respect to N eu, where u is the mutation rate. Applications of these results to the evolution of genetic variability within and between inbred lines are discussed.

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