scholarly journals MUTATION RATES, POPULATION SIZES AND AMOUNTS OF ELECTROPHORETIC VARIATION OF ENZYME LOCI IN NATURAL POPULATIONS

Genetics ◽  
1979 ◽  
Vol 92 (2) ◽  
pp. 623-646
Author(s):  
E Zouros
Keyword(s):  
Allelic Variation ◽  
Natural Populations ◽  
Purifying Selection ◽  
Mutation Rates ◽  
Electrophoretic Variation ◽  
Effective Population ◽  
Molecular Weights ◽  
Enzyme Subunits ◽  
Population Sizes ◽  
Infinite Alleles Model

ABSTRACT A method is presented for estimating relative mutation rates or relative effective population sizes, under the hypothesis of adaptively neutral allelic variation. This method was applied to seven surveys of electrophoretic variation. It was observed that electrophoretic mutation rates so obtained follow the gamma distribution and, in Drosophila, are positively correlated with the molecular weights of the enzyme subunits. The variance in mutation rate is larger under the step-wise model of electrophoretic mutation than under the infinite-alleles model. Rates for the most variable loci may exceed rates for less variable loci by a factor of 500. For completely invariant loci, this factor may be as high as 4 × 104, an observation suggesting that these loci are subject to purifying selection. In contrast to mutation rates, effective population sizes may vary at the most by a factor of ten. These results support the hypothesis that differences in the amount of electrophoretic variability among polymorphic loci may reflect differences in the rate by which electrophoretically detectable variation is generated in populations.

scholarly journals Changes in life history and population size can explain the relative neutral diversity levels on X and autosomes in extant human populations

2020 ◽  
Vol 117 (33) ◽  
pp. 20063-20069
Author(s):  
Guy Amster ◽  
David A. Murphy ◽  
William R. Milligan ◽  
Guy Sella
Keyword(s):  
Life History ◽  
Population Size ◽  
Mutation Rates ◽  
Human Populations ◽  
Effective Population ◽  
Mutation Bias ◽  
Female Ratio ◽  
Generation Times ◽  
Population Sizes ◽  
Male Mutation Bias

In human populations, the relative levels of neutral diversity on the X and autosomes differ markedly from each other and from the naïve theoretical expectation of 3/4. Here we propose an explanation for these differences based on new theory about the effects of sex-specific life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly longer generation times in males than in females, are expected to have had multiple effects on human X-to-autosome (X:A) diversity ratios, as a result of male-biased mutation rates, the equilibrium X:A ratio of effective population sizes, and the differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for male mutation bias results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal that X:A ratios of effective population sizes are considerably greater than previously appreciated. Finally, we find that the joint effects of historical changes in life history and population size can explain the observed X:A diversity ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous, that non-African populations experienced a substantial reduction in polygyny and/or increase in the male-to-female ratio of generation times around the Out-of-Africa bottleneck, and that current diversity levels were affected by fairly recent changes in sex-specific life history.

scholarly journals The infinite alleles model revisited: a Gibbs sampling approach

2021 ◽  
Author(s):  
Marc Manceau
Keyword(s):  
Viral Sequence ◽  
Mutation Process ◽  
Effective Population ◽  
Viral Genomes ◽  
Joint Reconstruction ◽  
The Past ◽  
Simplifying Assumptions ◽  
Population Sizes ◽  
New Perspective ◽  
Infinite Alleles Model

The SARS-CoV-2 outbreak started in late 2019 in the Hubei province in China and the first viral sequence was made available to the scientific community on early January 2020. From there, viral genomes from all over the world have followed at an outstanding rate, reaching already more than 10^5 on early May 2020, and more than 10^6 by early March 2021. Phylodynamics methods have been designed in recent years to process such datasets and infer population dynamics and sampling intensities in the past. However, the unprecedented scale of the SARS-CoV-2 dataset now calls for new methodological developments, relying e.g. on simplifying assumptions of the mutation process. In this article, I build on the infinite alleles model stemming from the field of population genetics to develop a new Bayesian statistical method allowing the joint reconstruction of the outbreak's effective population sizes and sampling intensities through time. This relies on prior conjugacy properties that prove useful both to develop a Gibbs sampler and to gain intuition on the way different parameters of the model are linked and inferred. I finally illustrate the use of this method on SARS-CoV-2 genomes sequenced during the first wave of the outbreak in four distinct European countries, thus offering a new perspective on the evolution of the sampling intensity through time in these countries from genetic data only.

scholarly journals Demographic inference through approximate-Bayesian-computation skyline plots

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3530 ◽  
Author(s):  
Miguel Navascués ◽  
Raphaël Leblois ◽  
Concetta Burgarella
Keyword(s):  
Approximate Bayesian Computation ◽  
Graphical Representation ◽  
A Priori ◽  
Natural Populations ◽  
Composite Likelihood ◽  
Bayesian Computation ◽  
Mathematical Function ◽  
Effective Population ◽  
Population Sizes ◽  
Approximate Bayesian

The skyline plot is a graphical representation of historical effective population sizes as a function of time. Past population sizes for these plots are estimated from genetic data, without a priori assumptions on the mathematical function defining the shape of the demographic trajectory. Because of this flexibility in shape, skyline plots can, in principle, provide realistic descriptions of the complex demographic scenarios that occur in natural populations. Currently, demographic estimates needed for skyline plots are estimated using coalescent samplers or a composite likelihood approach. Here, we provide a way to estimate historical effective population sizes using an Approximate Bayesian Computation (ABC) framework. We assess its performance using simulated and actual microsatellite datasets. Our method correctly retrieves the signal of contracting, constant and expanding populations, although the graphical shape of the plot is not always an accurate representation of the true demographic trajectory, particularly for recent changes in size and contracting populations. Because of the flexibility of ABC, similar approaches can be extended to other types of data, to multiple populations, or to other parameters that can change through time, such as the migration rate.

scholarly journals Conservation aspects of natural populations and captive-bred stocks of turbot (Scophthalmus maximus) and Dover sole (Solea solea) using estimates of genetic diversity

2007 ◽  
Vol 64 (6) ◽  
pp. 1173-1181 ◽  
Author(s):  
Athanasios Exadactylos ◽  
Mark J. Rigby ◽  
Audrey J. Geffen ◽  
John P. Thorpe
Keyword(s):  
Genetic Diversity ◽  
Population Structure ◽  
Natural Populations ◽  
Genetic Data ◽  
Scophthalmus Maximus ◽  
Effective Population ◽  
Solea Solea ◽  
Population Sizes ◽  
Turbot Scophthalmus Maximus ◽  
Dover Sole

Exadactylos, A., Rigby, M. J., Geffen, A. J., and Thorpe, J. P. 2007. Conservation aspects of natural populations and captive-bred stocks of turbot (Scophthalmus maximus) and Dover sole (Solea solea) using estimates of genetic diversity. – ICES Journal of marine Science, 64: 1173–1181. Population genetic analyses have been highly successful in predicting inter- and intraspecific evolutionary relationships, levels of gene flow, genetic divergence, and effective population sizes. Parameters estimated are evolutionary averages and are therefore relevant for addressing contemporary ecological or conservation issues. Changes in genetic variation within the range of a species may indicate patterns of population structure resulting from past ecological and demographic events that are otherwise difficult to infer, so may provide an insight into evolutionary development. Genetic data, drawn from 14 enzyme loci amplified from two populations of turbot (Scophthalmus maximus) and five populations of Dover sole (Solea solea) from the Irish Sea were used to examine population structure estimated from measures of genetic diversity. The aim was to provide an empirical assessment of whether artificial propagation poses a genetic threat to conservation of naturally spawning populations, and whether the fitness for natural spawning and rearing can be rapidly and substantially reduced or increased by artificial propagation. Because of prolonged overfishing, turbot and sole populations in the region are below natural levels, and survive in small local populations in fragmented habitats. Genetic data derived from allozymes have shown that populations are characterized by relatively low levels of genetic diversity. A hypothetical model supporting genetic population substructure, such as range expansion with founder-flush effects, and subsequent population decline with small effective population sizes was considered. Observations support our belief that conservation measures based on genetic diversity have to be developed to ensure the survival of this diverse gene pool.

scholarly journals Factors affecting levels of genetic diversity in natural populations

1998 ◽  
Vol 353 (1366) ◽  
pp. 177-186 ◽  
Author(s):  
William Amos ◽  
John Harwood
Keyword(s):  
Population Size ◽  
Large Population ◽  
Natural Populations ◽  
Base Material ◽  
Elephant Seal ◽  
Simple Relationship ◽  
Effective Population ◽  
Northern Elephant Seal ◽  
A Genome ◽  
Population Sizes

Genetic variability is the clay of evolution, providing the base material on which adaptation and speciation depend. It is often assumed that most interspecific differences in variability are due primarily to population size effects, with bottlenecked populations carrying less variability than those of stable size. However, we show that population bottlenecks are unlikely to be the only factor, even in classic case studies such as the northern elephant seal and the cheetah, where genetic polymorphism is virtually absent. Instead, we suggest that the low levels of variability observed in endangered populations are more likely to result from a combination of publication biases, which tend to inflate the level of variability which is considered ‘normal’, and inbreeding effects, which may hasten loss of variability due to drift. To account for species with large population sizes but low variability we advance three hypotheses. First, it is known that certain metapopulation structures can result in effective population sizes far below the census size. Second, there is increasing evidence that heterozygous sites mutate more frequently than equivalent homozygous sites, plausibly because mismatch repair between homologous chromosomes during meiosis provides extra opportunities to mutate. Such a mechanism would undermine the simple relationship between heterozygosity and effective population size. Third, the fact that related species that differ greatly in variability implies that large amounts of variability can be gained or lost rapidly. We argue that such cases are best explained by rapid loss through a genome–wide selective sweep, and suggest a mechanism by which this could come about, based on forced changes to a control gene inducing coevolution in the genes it controls. Our model, based on meiotic drive in mammals, but easily extended to other systems, would tend to facilitate population isolation by generating molecular incompatabilities. Circumstances can even be envisioned in which the process could provide intrinsic impetus to speciation.

scholarly journals Neo-sex chromosomes, genetic diversity and demographic history in the Critically Endangered Raso lark

2019 ◽  
Author(s):  
Elisa Dierickx ◽  
Simon Sin ◽  
Pieter van Veelen ◽  
M. de L. Brooke ◽  
Yang Liu ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Population Size ◽  
Sex Chromosomes ◽  
Allelic Variation ◽  
Demographic History ◽  
Large Population ◽  
Effective Population ◽  
Island Species ◽  
Population Sizes ◽  
Genetic Signatures

ABSTRACTSmall effective population sizes could expose island species to inbreeding and loss of genetic variation. Here we investigate factors shaping genetic diversity in the Raso lark, which has been restricted to a single islet for ~500 years, with a population size of a few hundred. We assembled a reference genome for the related Eurasian skylark and then assessed diversity and demographic history using RAD-seq data (75 samples from Raso larks and two related mainland species). We first identify broad tracts of suppressed recombination in females, indicating enlarged neo-sex chromosomes. It is plausible that these regions might inadvertently and temporarily preserve pre-existing allelic variation in females that would otherwise be lost through genetic drift. We then show that genetic diversity across autosomes in the Raso lark is lower than in its mainland relatives, but inconsistent with long-term persistence at its current population size. Finally, we find that genetic signatures of the recent population contraction are overshadowed by an ancient expansion and persistence of a very large population until the human settlement of Cape Verde. Our findings show how genome-wide approaches to study endangered species can help avoid confounding effects of genome architecture on diversity estimates, and how present day diversity can be shaped by ancient demographic events.

scholarly journals Striking differences in patterns of germline mutation between mice and humans

2016 ◽  
Author(s):  
Sarah J. Lindsay ◽  
Raheleh Rahbari ◽  
Joanna Kaplanis ◽  
Thomas Keane ◽  
Matthew E. Hurles
Keyword(s):  
Mutation Rate ◽  
Germline Mutation ◽  
Purifying Selection ◽  
Germline Mutations ◽  
Spermatogonial Stem Cell ◽  
Paternal Age ◽  
Effective Population ◽  
Population Sizes ◽  
Species Specific ◽  
Biological Differences

SummaryRecent whole genome sequencing (WGS) studies have estimated that the human germline mutation rate per basepair per generation (∼1.2−10−8) 1,2 is substantially higher than in mice (3.5-5.4−10−9) 3,4, which has been attributed to more efficient purifying selection due to larger effective population sizes in mice compared to humans.5,6,7. In humans, most germline mutations are paternal in origin and the numbers of mutations per offspring increase markedly with paternal age 2,8,9 and more weakly with maternal age 10. Germline mutations can arise at any stage of the cellular lineage from zygote to gamete, resulting in mutations being represented in different proportion and types of cells, with the earliest embryonic mutations being mosaic in both somatic and germline cells. Here we use WGS of multi-sibling mouse and human pedigrees to show striking differences in germline mutation rate and spectra between the two species, including a dramatic reduction in mutation rate in human spermatogonial stem cell (SSC) divisions, which we hypothesise was driven by selection. The differences we observed between mice and humans result from both biological differences within the same stage of embryogenesis or gametogenesis and species-specific differences in cellular genealogies of the germline.

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 Demographic Genetics of Brown Trout (Salmo trutta) and Estimation of Effective Population Size From Temporal Change of Allele Frequencies

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1369-1381 ◽  
Author(s):  
Per Erik Jorde ◽  
Nils Ryman
Keyword(s):  
Allele Frequency ◽  
Brown Trout ◽  
Salmo Trutta ◽  
Natural Populations ◽  
Effective Size ◽  
Effective Population ◽  
Frequency Shifts ◽  
Brown Trout Salmo Trutta ◽  
Population Sizes ◽  
Allozyme Loci

Abstract We studied temporal allele frequency shifts over 15 years and estimated the genetically effective size of four natural populations of brown trout (Salmo trutta L.) on the basis of the variation at 14 polymorphic allozyme loci. The allele frequency differences between consecutive cohorts were significant in all four populations. There were no indications of natural selection, and we conclude that random genetic drift is the most likely cause of temporal allele frequency shifts at the loci examined. Effective population sizes were estimated from observed allele frequency shifts among cohorts, taking into consideration the demographic characteristics of each population. The estimated effective sizes of the four populations range from 52 to 480 individuals, and we conclude that the effective size of natural brown trout populations may differ considerably among lakes that are similar in size and other apparent characteristics. In spite of their different effective sizes all four populations have similar levels of genetic variation (average heterozygosity) indicating that excessive loss of genetic variability has been retarded, most likely because of gene flow among neighboring populations.

scholarly journals Changes in life history and population size can explain relative neutral diversity levels on X and autosomes in extant human populations

2019 ◽  
Author(s):  
Guy Amster ◽  
David A. Murphy ◽  
William M. Milligan ◽  
Guy Sella
Keyword(s):  
Life History ◽  
Population Size ◽  
Mutation Rates ◽  
Human Populations ◽  
Effective Population ◽  
Mutation Bias ◽  
Historical Changes ◽  
Generation Times ◽  
Population Sizes ◽  
Male Mutation Bias

AbstractIn human populations, relative levels of neutral polymorphism on the X and autosomes differ markedly from each other and from the naive theoretical expectation of ¾. These differences have attracted considerable attention, with studies highlighting several potential causes, including male biased mutation and reproductive variance, historical changes in population size, and selection at linked loci. We revisit this question in light of our new theory about the effects of life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly higher generation times in males than females, likely had multiple effects on human X-to-autosomes (X:A) polymorphism ratios, through the extent of male mutation bias, the equilibrium X:A ratios of effective population sizes, and differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for the male bias in mutation results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal X:A ratios of effective population sizes to be considerably greater than previously appreciated. We then show that the joint effects of historical changes in life history and population size can explain X:A polymorphism ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous; that non-African populations experienced a substantial reduction in polygyny and/or increase in male-biased generation times around the out of Africa bottleneck; and that extant diversity levels were affected by fairly recent changes in sex-specific life history.Significance StatementAll else being equal, the ratio of diversity levels on X and autosomes at selectively neutral sites should mirror the ratio of their numbers in the population and thus equal ¾. In reality, the ratios observed across human populations differ markedly from ¾ and from each other. Because from a population perspective, autosomes spend an equal number of generations in both sexes while the X spends twice as many generations in females, these departures from the naïve expectations likely reflect differences between male and female life histories and their effects on mutation processes. Indeed, we show that the ratios observed across human populations can be explained by demographic history, assuming plausible, sex-specific mutation rates, generation times and reproductive variances.

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