Theoretical Analysis of Electrophoretically Detectable Polymorphisms: Models of Very Slightly Deleterious Mutations

1975 ◽  
Vol 109 (966) ◽  
pp. 137-145 ◽  
Author(s):  
Tomoko Ohta ◽  
Motoo Kimura
Keyword(s):  
Theoretical Analysis ◽  
Deleterious Mutations ◽  
Slightly Deleterious 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 Selective strolls: fixation and extinction in diploids are slower for weakly selected mutations than for neutral ones

2015 ◽  
Author(s):  
fabrizio mafessoni ◽  
Michael Lachmann
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Low Frequency ◽  
Evolutionary Process ◽  
Deleterious Mutations ◽  
Finite Populations ◽  
Slightly Deleterious Mutations ◽  
Getting Lost ◽  
Genetic Signatures ◽  
Diploid Populations

In finite populations, an allele disappears or reaches fixation due to two main forces, selection and drift. Selection is generally thought to accelerate the process: a selected mutation will reach fixation faster than a neutral one, and a disadvantageous one will quickly disappear from the population. We show that even in simple diploid populations, this is often not true. Dominance and recessivity unexpectedly slow down the evolutionary process for weakly selected alleles. In particular, slightly advantageous dominant and mildly deleterious recessive mu- tations reach fixation more slowly than neutral ones. This phenomenon determines genetic signatures opposite to those expected under strong selection, such as increased instead of decreased genetic diversity around the selected site. Furthermore, we characterize a new phenomenon: mildly deleterious recessive alleles, thought to represent the vast majority of newly arising mutations, survive in a population longer than neutral ones, before getting lost. Hence, natural selection is less effective than previously thought in getting rid rapidly of slightly negative mutations, contributing their observed persistence in present populations. Consequently, low frequency slightly deleterious mutations are on average older than neutral ones.

scholarly journals Evolution of Drift Robustness in Small Populations

2016 ◽  
Author(s):  
Thomas LaBar ◽  
Christoph Adami
Keyword(s):  
Mathematical Modeling ◽  
Experimental Evolution ◽  
Small Population ◽  
Small Populations ◽  
Mutational Load ◽  
Deleterious Mutations ◽  
Mutational Robustness ◽  
Large Populations ◽  
Slightly Deleterious Mutations ◽  
Population Sizes

AbstractMost mutations are deleterious and cause a reduction in population fitness known as the mutational load. In small populations, weakened selection against slightly-deleterious mutations results in an additional fitness reduction. Many studies have established that populations can evolve a reduced mutational load by evolving mutational robustness, but it is uncertain whether small populations can evolve a reduced susceptibility to drift-related fitness declines. Here, using mathematical modeling and digital experimental evolution, we show that small populations do evolve a reduced vulnerability to drift, or “drift robustness”. We find that, compared to genotypes from large populations, genotypes from small populations have a decreased likelihood of small-effect deleterious mutations, thus causing small-population genotypes to be drift-robust. We further show that drift robustness is not adaptive, but instead arises because small populations preferentially adapt to drift-robust fitness peaks. These results have implications for genome evolution in organisms with small population sizes.

scholarly journals An Experimental Test for Synergistic Epistasis and Its Application in Chlamydomonas

Genetics ◽  
1997 ◽  
Vol 145 (3) ◽  
pp. 815-819 ◽  
Author(s):  
J A G M Arjan de Visser ◽  
Rolf F Hoekstra ◽  
Herman van den Ende
Keyword(s):  
Carrying Capacity ◽  
Maximum Growth ◽  
Maximum Growth Rate ◽  
Skewed Distribution ◽  
Logistic Growth ◽  
Deleterious Mutations ◽  
General Observation ◽  
Slightly Deleterious Mutations ◽  
Independent Effects ◽  
Two Parameters

Theoretically, one of the most general benefits of sex is given by its function in facilitating selection against deleterious mutations. This advantage of sex may be deterministic if deleterious mumtiom affect the fitness of an individual in a synergistic way, i.e., if mutations increase each others' negative fitness effect. We present a new test for synergistic epistasis that considers the skewnessof the log fitness distribution of offspring from a cross. We applied this test to data of the unicellular alga Chlamydomonas moewussii. For this purpose, two crosses were made: one between two strains that are presumed to have accumulated slightly deleterious mutations, the other between two strains without a history of mutation accumulation. Fitness was measured by estimating the two parameters of logistic growth in batch culture, the maximum growth rate (r) and the carrying capacity (K). The finding of a negatively skewed distribution for K in the accumulation cross suggests synergism between mutations affecting the carrying capacity, while the absence of skewness for r in both crosses is consistent with independent effects of mutations affecting this parameter. The results suggest a possible alternative explanation for the general observation that sex is related to constant environments, where selection on K predominates, while asexual reproduction is found in more variable environments, where selection on r is more important.

scholarly journals asymptoticMK: A web-based tool for the asymptotic McDonald–Kreitman test

2017 ◽  
Author(s):  
Benjamin C. Haller ◽  
Philipp W. Messer
Keyword(s):  
Web Service ◽  
Test Results ◽  
Deleterious Mutations ◽  
Reference Region ◽  
Web Based ◽  
Genomic Test ◽  
Mk Test ◽  
Test Region ◽  
Slightly Deleterious Mutations

ABSTRACTThe McDonald–Kreitman (MK) test is a widely used method for quantifying the role of positive selection in molecular evolution. One key shortcoming of this test lies in its sensitivity to the presence of slightly deleterious mutations, which can severely bias its estimates. An asymptotic version of the MK test was recently introduced that addresses this problem by evaluating polymorphism levels for different mutation frequencies separately, and then extrapolating a function fitted to that data. Here we present asymptoticMK, a web-based implementation of this asymptotic McDonald–Kreitman test. Our web service provides a simple R-based interface into which the user can upload the required data (polymorphism and divergence data for the genomic test region and a neutrally evolving reference region). The web service then analyzes the data and provides plots of the test results. This service is free to use, open-source, and available at http://benhaller.com/messerlab/asymptoticMK.html.

scholarly journals A Conservative Test of Genetic Drift in the Endosymbiotic Bacterium Buchnera: Slightly Deleterious Mutations in the Chaperonin groEL

Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 1651-1660
Author(s):  
Joshua T Herbeck ◽  
Daniel J Funk ◽  
Patrick H Degnan ◽  
Jennifer J Wernegreen
Keyword(s):  
Genetic Drift ◽  
Balancing Selection ◽  
Purifying Selection ◽  
Nonsynonymous Substitution ◽  
Maximum Likelihood Estimates ◽  
Sequence Evolution ◽  
Endosymbiotic Bacterium ◽  
Deleterious Mutations ◽  
Synonymous Polymorphism ◽  
Slightly Deleterious Mutations

Abstract The obligate endosymbiotic bacterium Buchnera aphidicola shows elevated rates of sequence evolution compared to free-living relatives, particularly at nonsynonymous sites. Because Buchnera experiences population bottlenecks during transmission to the offspring of its aphid host, it is hypothesized that genetic drift and the accumulation of slightly deleterious mutations can explain this rate increase. Recent studies of intraspecific variation in Buchnera reveal patterns consistent with this hypothesis. In this study, we examine inter- and intraspecific nucleotide variation in groEL, a highly conserved chaperonin gene that is constitutively overexpressed in Buchnera. Maximum-likelihood estimates of nonsynonymous substitution rates across Buchnera species are strikingly low at groEL compared to other loci. Despite this evidence for strong purifying selection on groEL, our intraspecific analysis of this gene documents reduced synonymous polymorphism, elevated nonsynonymous polymorphism, and an excess of rare alleles relative to the neutral expectation, as found in recent studies of other Buchnera loci. Comparisons with Escherichia coli generally show patterns predicted by their differences in Ne. The sum of these observations is not expected under relaxed or balancing selection, selective sweeps, or increased mutation rate. Rather, they further support the hypothesis that drift is an important force driving accelerated protein evolution in this obligate mutualist.

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