scholarly journals The effect of deleterious mutations on neutral molecular variation.

Genetics ◽  
1993 ◽  
Vol 134 (4) ◽  
pp. 1289-1303 ◽  
Author(s):  
B Charlesworth ◽  
M T Morgan ◽  
D Charlesworth
Keyword(s):  
Genetic Recombination ◽  
Random Mating ◽  
Large Population ◽  
Molecular Variation ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Deleterious Alleles ◽  
The Mean ◽  
Site Diversity ◽  
Neutral Mutations

Abstract Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral sites. This is because a new neutral variant can only remain in a large population for a long period of time if it is maintained in gametes that are free of deleterious alleles, and hence are not destined for rapid elimination from the population by selection. Approximate formulas are derived for the reduction below classical neutral values resulting from such background selection against deleterious mutations, for the mean times to fixation and loss of new mutations, nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a given selection regime and mating system, the reduction is an exponential function of the total mutation rate to deleterious mutations for the section of the genome involved. Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of outcrossing. The mean time to loss of new neutral mutations and the total number of segregating neutral sites are less sensitive to background selection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical neutral result. Observed reductions in molecular variation in low recombination genomic regions of sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in highly selfing plant populations, may be partly due to background selection against deleterious mutations.

scholarly journals MAINTENANCE OF GENETIC VARIABILITY UNDER THE PRESSURE OF NEUTRAL AND DELETERIOUS MUTATIONS IN A FINITE POPULATION

Genetics ◽  
1979 ◽  
Vol 92 (2) ◽  
pp. 647-667
Author(s):  
Wen-Hsiung Li
Keyword(s):  
Frequency Spectrum ◽  
Intermediate Frequency ◽  
Deleterious Mutations ◽  
Low Frequencies ◽  
Deleterious Alleles ◽  
Genic Variation ◽  
Controversial Problem ◽  
The Mean ◽  
Neutral Mutations ◽  
A Minor

ABSTRACT In order to assess the effect of deleterious mutations on various measures of genic variation, approximate formulas have been developed for the frequency spectrum, the mean number of alleles in a sample, and the mean homozy-gosity; in some particular cases, exact formulas have been obtained. The assumptions made are that two classes of mutations exist, neutral and deleterious, and that selection is strong enough to keep deleterious alleles in low frequencies, the mode of selection being either genic or recessive. The main findings are: (1) If the expected value () of the sum of the frequencies of deleterious alleles is about 10% or less, then the presence of deleterious alleles causes only a minor reduction in the mean number of neutral alleles ir, a sample, as compared to the case of = 0. Also, the low- and intermediate-frequency parts of the frequency spectrum of neutral alleles are little affected by the presence of deleterious alleles, though the high-frequency part may be changed drastically. (2) The contribution of deleterious mutations to the expected total number of alleles in a sample can be quite large even if is only 1 or 2%. (3) The mean homozygosity is roughly equal to (1-2)/(1+λ  1), where λ  1, is twice the number of new neutral mutations occurring in each generation in the total population. Thus, deleterious mutations increase the mean heterozygosity by about 2/ (1 +λ  1). The present results have been applied to study the controversial problem of how deleterious mutations may affect the testing of the neutral mutation hypothesis.

scholarly journals The effects of weak selection on neutral diversity at linked sites

2021 ◽  
Author(s):  
Brian Charlesworth
Keyword(s):  
Theoretical Models ◽  
Population Variation ◽  
Deleterious Mutations ◽  
Weak Selection ◽  
The Mean ◽  
Frequency Changes ◽  
Site Diversity ◽  
Neutral Mutations ◽  
Approximate Expressions

The effects of selection on variability at linked sites have an important influence on levels and patterns of within-population variation across the genome. Most theoretical models of these effects have assumed that selection is sufficiently strong that allele frequency changes at the loci concerned are largely deterministic. These models have led to the conclusion that directional selection for new selectively favorable mutations, or against recurrent deleterious mutations, reduces nucleotide site diversity at linked neutral sites. Recent work has shown, however, that fixations of weakly selected mutations, accompanied by significant stochastic changes in allele frequencies, can sometimes cause higher diversity at linked sites when compared with the effects of fixations of neutral mutations. The present paper extends this work by deriving approximate expressions for the mean times to loss and fixation of mutations subject to selection, and analysing the conditions under which selection increases rather than reduces these times. Simulations are used to examine the relations between diversity at a neutral site and the fixation and loss times of mutations at a linked site subject to selection. It is shown that the long-term level of neutral diversity can be increased over the equilibrium expectation in the absence of selection by recurrent fixations and losses of linked, weakly selected dominant or partially dominant favorable mutations, and by linked recessive or partially recessive deleterious mutations. The results are used to examine the conditions under which associative overdominance, as opposed to background selection, is likely to operate.

scholarly journals The effect of recombination on background selection

1996 ◽  
Vol 67 (2) ◽  
pp. 159-174 ◽  
Author(s):  
Magnus Nordborg ◽  
Brian Charlesworth ◽  
Deborah Charlesworth
Keyword(s):  
Genetic Recombination ◽  
Random Mating ◽  
Large Population ◽  
Approximate Equation ◽  
Arbitrary Distribution ◽  
Background Selection ◽  
Weak Selection ◽  
Recombination Rates ◽  
Neutral Locus ◽  
Wide Range

SummaryAn approximate equation is derived, which predicts the effect on variability at a neutral locus of background selection due to a set of partly linked deleterious mutations. Random mating, multiplicative fitnesses, and sufficiently large population size that the selected loci are in mutation/selection equilibrium are assumed. Given these assumptions, the equation is valid for an arbitrary genetic map, and for an arbitrary distribution of selection coefficients across loci. Monte Carlo computer simulations show that the formula performs well for small population sizes under a wide range of conditions, and even seems to apply when there are epistatic fitness interactions among the selected loci. Failure occurred only with very weak selection and tight linkage. The formula is shown to imply that weakly selected mutations are more likely than strongly selected mutations to produce regional patterning of variability along a chromosome in response to local variation in recombination rates. Loci at the extreme tip of a chromosome experience a smaller effect of background selection than loci closer to the centre. It is shown that background selection can produce a considerable overall reduction in variation in organisms with small numbers of chromosomes and short maps, such as Drosophila. Large overall effects are less likely in species with higher levels of genetic recombination, such as mammals, although local reductions in regions of reduced recombination might be detectable.

The Age of Nonsynonymous and Synonymous Mutations in Animal mtDNA and Implications for the Mildly Deleterious Theory

Genetics ◽  
1999 ◽  
Vol 153 (1) ◽  
pp. 497-506 ◽  
Author(s):  
Rasmus Nielsen ◽  
Daniel M Weinreich
Keyword(s):  
Dna Sequences ◽  
Purifying Selection ◽  
Data Sets ◽  
Deleterious Mutations ◽  
Synonymous Mutations ◽  
Weak Evidence ◽  
Mitochondrial Data ◽  
The Mean ◽  
Excess Number ◽  
Neutral Mutations

Abstract McDonald/Kreitman tests performed on animal mtDNA consistently reveal significant deviations from strict neutrality in the direction of an excess number of polymorphic nonsynonymous sites, which is consistent with purifying selection acting on nonsynonymous sites. We show that under models of recurrent neutral and deleterious mutations, the mean age of segregating neutral mutations is greater than the mean age of segregating selected mutations, even in the absence of recombination. We develop a test of the hypothesis that the mean age of segregating synonymous mutations equals the mean age of segregating nonsynonymous mutations in a sample of DNA sequences. The power of this age-of-mutation test and the power of the McDonald/Kreitman test are explored by computer simulations. We apply the new test to 25 previously published mitochondrial data sets and find weak evidence for selection against nonsynonymous mutations.

scholarly journals The effect of background selection against deleterious mutations on weakly selected, linked variants

1994 ◽  
Vol 63 (3) ◽  
pp. 213-227 ◽  
Author(s):  
Brian Charlesworth
Keyword(s):  
Genetic Diversity ◽  
Molecular Evolution ◽  
Effective Size ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Deleterious Alleles ◽  
Rates Of Evolution ◽  
Selection Approach ◽  
Slightly Deleterious Mutations ◽  
Neutral Case

SummaryThis paper analyses the effects of selection against deleterious alleles maintained by mutation (‘ background selection’) on rates of evolution and levels of genetic diversity at weakly selected, completely linked, loci. General formulae are derived for the expected rates of gene substitution and genetic diversity, relative to the neutral case, as a function of selection and dominance coefficients at the loci in question, and of the frequency of gametes that are free of deleterious mutations with respect to the loci responsible for background selection. As in the neutral case, most effects of background selection can be predicted by considering the effective size of the population to be multiplied by the frequency of mutation-free gametes. Levels of genetic diversity can be sharply reduced by background selection, with the result that values for sites under selection approach those for neutral variants subject to the same regime of background selection. Rates of fixation of slightly deleterious mutations are increased by background selection, and rates of fixation of advantageous mutations are reduced. The properties of sex-linked and autosomal asexual and self-fertilizing populations are considered. The implications of these results for the interpretation of studies of molecular evolution and variation are discussed.

scholarly journals The effect of strong purifying selection on genetic diversity

2017 ◽  
Author(s):  
Ivana Cvijović ◽  
Benjamin H. Good ◽  
Michael M. Desai
Keyword(s):  
Genetic Diversity ◽  
Frequency Spectrum ◽  
Purifying Selection ◽  
Genomic Diversity ◽  
Small Samples ◽  
Direct Selection ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Site Frequency Spectrum ◽  
Neutral Mutations

Purifying selection reduces genetic diversity, both at sites under direct selection and at linked neutral sites. This process, known as background selection, is thought to play an important role in shaping genomic diversity in natural populations. Yet despite its importance, the effects of background selection are not fully understood. Previous theoretical analyses of this process have taken a backwards-time approach based on the structured coalescent. While they provide some insight, these methods are either limited to very small samples or are computationally prohibitive. Here, we present a new forward-time analysis of the trajectories of both neutral and deleterious mutations at a nonrecombining locus. We find that strong purifying selection leads to remarkably rich dynamics: neutral mutations can exhibit sweep-like behavior, and deleterious mutations can reach substantial frequencies even when they are guaranteed to eventually go extinct. Our analysis of these dynamics allows us to calculate analytical expressions for the full site frequency spectrum. We find that whenever background selection is strong enough to lead to a reduction in genetic diversity, it also results in substantial distortions to the site frequency spectrum, which can mimic the effects of population expansions or positive selection. Because these distortions are most pronounced in the low and high frequency ends of the spectrum, they become particularly important in larger samples, but may have small effects in smaller samples. We also apply our forward-time framework to calculate other quantities, such as the ultimate fates of polymorphisms or the fitnesses of their ancestral backgrounds.

The Impact of Lethal Recessive Alleles on Bottlenecks with Implications for Conservation Genetics

2016 ◽  
Author(s):  
R. B. Campbell
Keyword(s):  
Large Population ◽  
Genetic Load ◽  
Ancestral Population ◽  
Deleterious Mutations ◽  
Recessive Mutations ◽  
Deleterious Alleles ◽  
Endangered Population ◽  
Population Breeding ◽  
The Cost ◽  
The Impact

AbstractWhen a bottleneck occurs, lethal recessive alleles from the ancestral population provide a genetic load. The purging of lethal recessive mutations may prolong the bottleneck, or even cause the population to become extinct. But the purging is of short duration, it will be over before near neutral deleterious alleles accumulate. Lethal recessive alleles from the parental population and near neutral deleterious mutations which occur during a bottleneck are temporally separated threats to the survival of a population. Breeding individuals from a large population into a small endangered population will provide the benefit of viable alleles to replace near neutral deleterious alleles but also the cost of lethal recessive mutations from the large population.

scholarly journals An Adaptive Hypothesis for the Evolution of the Y Chromosome

Genetics ◽  
1998 ◽  
Vol 150 (4) ◽  
pp. 1693-1698 ◽  
Author(s):  
H Allen Orr ◽  
Yuseob Kim
Keyword(s):  
Y Chromosome ◽  
Large Population ◽  
Overwhelming Majority ◽  
Background Selection ◽  
Deleterious Alleles ◽  
Y Chromosomes ◽  
Population Sizes ◽  
Probability Of Fixation

Abstract Population geneticists remain unsure of the forces driving the evolution of Y chromosomes. Here we consider the possibility that the degeneration of the Y reflects its inability to evolve adaptively. Because the overwhelming majority of favorable mutations on a nonrecombining proto-Y suffer a zero probability of fixation, the fitness of the Y must lag far behind that of the recombining X. At some point, this disparity will grow so large that selection favors an increase in the expression of (fit) X-linked alleles and a decrease in the expression of (unfit) Y-linked alleles. Our calculations suggest that this process acts far more rapidly than hitchhiking-induced erosion of the Y and at least as rapidly as the fixation of deleterious alleles on the Y by background selection. Most important, this hypothesis can explain the evolution of Y chromosomes in taxa such as Drosophila that have very large population sizes.

Population fragmentation causes inadequate gene flow and increases extinction risk

2017 ◽  
Author(s):  
Richard Frankham ◽  
Jonathan D. Ballou ◽  
Katherine Ralls ◽  
Mark D. B. Eldridge ◽  
Michele R. Dudash ◽  
...  
Keyword(s):  
Gene Flow ◽  
Extinction Risk ◽  
Random Mating ◽  
Large Population ◽  
Isolated Population ◽  
Population Fragmentation ◽  
Single Population ◽  
Total Size ◽  
Limited Gene Flow

Most species now have fragmented distributions, often with adverse genetic consequences. The genetic impacts of population fragmentation depend critically upon gene flow among fragments and their effective sizes. Fragmentation with cessation of gene flow is highly harmful in the long term, leading to greater inbreeding, increased loss of genetic diversity, decreased likelihood of evolutionary adaptation and elevated extinction risk, when compared to a single population of the same total size. The consequences of fragmentation with limited gene flow typically lie between those for a large population with random mating and isolated population fragments with no gene flow.

scholarly journals Planetary Nebulae in M31: Abundances, and comparison with bright Planetary Nebulae in the LMC

1997 ◽  
Vol 180 ◽  
pp. 475-476
Author(s):  
M. G. Richer ◽  
G. Stasińska ◽  
M. L. McCall
Keyword(s):  
Planetary Nebula ◽  
Luminosity Function ◽  
Large Population ◽  
Wavelength Region ◽  
Planetary Nebulae ◽  
Surprising Result ◽  
Population Synthesis ◽  
Abundance Distribution ◽  
Wide Range ◽  
The Mean

We have obtained spectra of 28 planetary nebulae in the bulge of M31 using the MOS spectrograph at the Canada-France-Hawaii Telescope. Typically, we observed the [O II] λ3727 to He I λ5876 wavelength region at a resolution of approximately 1.6 å/pixel. For 19 of the 21 planetary nebulae whose [OIII]λ5007 luminosities are within 1 mag of the peak of the planetary nebula luminosity function, our oxygen abundances are based upon a measured [OIII]λ4363 intensity, so they are based upon a measured electron temperature. The oxygen abundances cover a wide range, 7.85 dex < 12 + log(O/H) < 9.09 dex, but the mean abundance is surprisingly low, 12 + log(O/H)–8.64 ± 0.32 dex, i.e., roughly half the solar value (Anders & Grevesse 1989). The distribution of oxygen abundances is shown in Figure 1, where the ordinate indicates the number of planetary nebulae with abundances within ±0.1 dex of any point on the x-axis. The dashed line indicates the mean abundance, and the dotted lines indicate the ±1 σ points. The shape of this abundance distribution seems to indicate that the bulge of M31 does not contain a large population of bright, oxygen-rich planetary nebulae. This is a surprising result, for various population synthesis studies (e.g., Bica et al. 1990) have found a mean stellar metallicity approximately 0.2 dex above solar. This 0.5 dex discrepancy leads one to question whether the mean stellar metallicity is as high as the population synthesis results indicate or if such metal-rich stars produce bright planetary nebulae at all. This could be a clue concerning the mechanism responsible for the variation in the number of bright planetary nebulae observed per unit luminosity in different galaxies (e.g., Hui et al. 1993).

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