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.

scholarly journals Transition from background selection to associative overdominance promotes diversity in regions of low recombination

2019 ◽  
Author(s):  
Kimberly J. Gilbert ◽  
Fanny Pouyet ◽  
Laurent Excoffier ◽  
Stephan Peischl
Keyword(s):  
Genetic Diversity ◽  
Balancing Selection ◽  
Purifying Selection ◽  
Heterozygote Advantage ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Recombination Rates ◽  
Locus Model ◽  
Genome Wide ◽  
Linked Selection

SummaryLinked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection, BGS, Charlesworth et al. 1993), creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD, Ohta 1971, Zhao & Charlesworth, 2016), due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao & Charlesworth (2016) identified the conditions when AOD should dominate over BGS in a single-locus model and suggested that the effect of AOD could become stronger if multiple linked deleterious variants co-segregate. We present a model describing how and under which conditions multi-locus dynamics can amplify the effects of AOD. We derive the conditions for a transition from BGS to AOD due to pseudo-overdominance (Ohta & Kimura 1970), i.e. a form of balancing selection that maintains complementary deleterious haplotypes that mask the effect of recessive deleterious mutations. Simulations confirm these findings and show that multi-locus AOD can increase diversity in low recombination regions much more strongly than previously appreciated. While BGS is known to drive genome-wide diversity in humans (Pouyet et al. 2018), the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 21 such regions in the human genome showing clear signals of multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low recombination regions of many species.

scholarly journals Intra-Species Differences in Population Size shape Life History and Genome Evolution

2019 ◽  
Author(s):  
David Willemsen ◽  
Rongfeng Cui ◽  
Martin Reichard ◽  
Dario Riccardo Valenzano
Keyword(s):  
Life History ◽  
Population Size ◽  
Genetic Drift ◽  
Sex Chromosome ◽  
Purifying Selection ◽  
Life History Trait ◽  
Deleterious Mutations ◽  
Effective Population ◽  
Annual Life Cycle ◽  
Evolutionary Forces

AbstractThe evolutionary forces shaping life history trait divergence within species are largely unknown. Killifish (oviparous Cyprinodontiformes) evolved an annual life cycle as an exceptional adaptation to life in arid savannah environments characterized by seasonal water availability. The turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate known to science and displays differences in lifespan among wild populations, representing an ideal natural experiment in the evolution and diversification of life history. Here, by combining genome sequencing and population genetics, we investigate the evolutionary forces shaping lifespan among turquoise killifish populations. We generate an improved reference assembly for the turquoise killifish genome, trace the evolutionary origin of the sex chromosome, and identify genes under strong positive and purifying selection, as well as those evolving neutrally. We find that the shortest-lived turquoise killifish populations, which dwell in fragmented and isolated habitats at the outer margin of the geographical range of the species, are characterized by small effective population size and accumulate throughout the genome several small to large-effect deleterious mutations due to genetic drift. The genes most affected by drift in the shortest-lived turquoise killifish populations are involved in the WNT signalling pathway, neurodegenerative disorders, cancer and the mTOR pathway. As the populations under stronger genetic drift are the shortest-lived ones, we propose that limited population size due to habitat fragmentation and repeated population bottlenecks, by causing the genome-wide accumulation of deleterious mutations, cumulatively contribute to the short adult lifespan in turquoise killifish populations.

scholarly journals Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection

2016 ◽  
Author(s):  
Tobias L. Lenz ◽  
Victor Spirin ◽  
Daniel M. Jordan ◽  
Shamil R. Sunyaev
Keyword(s):  
Balancing Selection ◽  
Purifying Selection ◽  
Physical Distance ◽  
Deleterious Mutations ◽  
Sequencing Data ◽  
Hla Genes ◽  
Deleterious Alleles ◽  
Whole Exome Sequencing Data ◽  
Elevated Frequency ◽  
Coding Variants

AbstractDeleterious mutations are expected to evolve under negative selection and are usually purged from the population. However, deleterious alleles segregate in the human population and some disease-associated variants are maintained at considerable frequencies. Here we test the hypothesis that balancing selection may counteract purifying selection in neighboring regions and thus maintain deleterious variants at higher frequency than expected from their detrimental fitness effect. We first show in realistic simulations that balancing selection reduces the density of polymorphic sites surrounding a locus under balancing selection, but at the same time markedly increases the population frequency of the remaining variants, including even substantially deleterious alleles. To test the predictions of our simulations empirically, we then use whole exome sequencing data from 6,500 human individuals and focus on the most established example for balancing selection in the human genome, the major histocompatibility complex (MHC). Our analysis shows an elevated frequency of putatively deleterious coding variants in non-HLA genes localized in the MHC region. The mean frequency of these variants declined with physical distance from the classical HLA genes, indicating dependency on genetic linkage. These results reveal an indirect cost of the genetic diversity maintained by balancing selection, which has hitherto been perceived as mostly advantageous, and have implications both for the evolution of recombination and also for the epidemiology of various MHC-associated diseases.

scholarly journals Genomics of a killifish from the Seychelles islands supports transoceanic island colonization and reveals relaxed selection of developmental genes

2020 ◽  
Author(s):  
Rongfeng Cui ◽  
Alexandra M Tyers ◽  
Zahabiya Juzar Malubhoy ◽  
Sadie Wisotsky ◽  
Stefano Valdesalici ◽  
...  
Keyword(s):  
Purifying Selection ◽  
Deleterious Mutations ◽  
Effective Population ◽  
Relaxed Selection ◽  
Annual Killifish ◽  
Tectonic Events ◽  
Genome Wide ◽  
Seychelles Islands ◽  
Slightly Deleterious Mutations ◽  
Selection Of

AbstractHow freshwater fish colonize remote islands remains an evolutionary puzzle. Tectonic drift and trans-oceanic dispersal models have been proposed as possible alternative mechanisms. Integrating dating of known tectonic events with population genetics and experimental test of salinity tolerance in the Seychelles islands golden panchax (Pachypanchax playfairii), we found support for trans-oceanic dispersal being the most likely scenario. At the macroevolutionary scale, the non-annual killifish golden panchax shows stronger genome-wide purifying selection compared to annual killifishes from continental Africa. Reconstructing past demographies in isolated golden panchax populations provides support for decline in effective population size, which could have allowed slightly deleterious mutations to segregate in the population. Unlike annual killifishes, where relaxed selection preferentially targets aging-related genes, relaxation of purifying selection in golden panchax affects genes involved in developmental processes, including fgf10.

scholarly journals Mutation bias reflects natural selection in Arabidopsis thaliana

Nature ◽  
2022 ◽  
Author(s):  
J. Grey Monroe ◽  
Thanvi Srikant ◽  
Pablo Carbonell-Bejerano ◽  
Claude Becker ◽  
Mariele Lensink ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
De Novo ◽  
Purifying Selection ◽  
Sequence Evolution ◽  
Deleterious Mutations ◽  
De Novo Mutations ◽  
Mutation Bias ◽  
Prevailing Paradigm ◽  
Genome Wide ◽  
Physical Features

AbstractSince the first half of the twentieth century, evolutionary theory has been dominated by the idea that mutations occur randomly with respect to their consequences1. Here we test this assumption with large surveys of de novo mutations in the plant Arabidopsis thaliana. In contrast to expectations, we find that mutations occur less often in functionally constrained regions of the genome—mutation frequency is reduced by half inside gene bodies and by two-thirds in essential genes. With independent genomic mutation datasets, including from the largest Arabidopsis mutation accumulation experiment conducted to date, we demonstrate that epigenomic and physical features explain over 90% of variance in the genome-wide pattern of mutation bias surrounding genes. Observed mutation frequencies around genes in turn accurately predict patterns of genetic polymorphisms in natural Arabidopsis accessions (r = 0.96). That mutation bias is the primary force behind patterns of sequence evolution around genes in natural accessions is supported by analyses of allele frequencies. Finally, we find that genes subject to stronger purifying selection have a lower mutation rate. We conclude that epigenome-associated mutation bias2 reduces the occurrence of deleterious mutations in Arabidopsis, challenging the prevailing paradigm that mutation is a directionless force in evolution.

The Effect of Selection on Genealogies

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 1115-1131 ◽  
Author(s):  
N H Barton ◽  
A M Etheridge
Keyword(s):  
Allele Frequency ◽  
Balancing Selection ◽  
Purifying Selection ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Selection Coefficient ◽  
Weak Selection ◽  
Random Drift ◽  
Genotype Frequencies ◽  
Coalescence Times

Abstract The coalescent process can describe the effects of selection at linked loci only if selection is so strong that genotype frequencies evolve deterministically. Here, we develop methods proposed by Kaplan, Darden, and Hudson to find the effects of weak selection. We show that the overall effect is given by an extension to Price’s equation: the change in properties such as moments of coalescence times is equal to the covariance between those properties and the fitness of the sample of genes. The distribution of coalescence times differs substantially between allelic classes, even in the absence of selection. However, the average coalescence time between randomly chosen genes is insensitive to the current allele frequency and is affected significantly by purifying selection only if deleterious mutations are common and selection is strong (i.e., the product of population size and selection coefficient, Ns > 3). Balancing selection increases mean coalescence times, but the effect becomes large only when mutation rates between allelic classes are low and when selection is extremely strong. Our analysis supports previous simulations that show that selection has surprisingly little effect on genealogies. Moreover, small fluctuations in allele frequency due to random drift can greatly reduce any such effects. This will make it difficult to detect the action of selection from neutral variation alone.

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 Balancing selection, genetic drift, and human‐mediated introgression interplay to shape MHC (functional) diversity in Mediterranean brown trout

2021 ◽  
Author(s):  
Lorenzo Talarico ◽  
Silvio Marta ◽  
Anna Rita Rossi ◽  
Simone Crescenzo ◽  
Gerardo Petrosino ◽  
...  
Keyword(s):  
Functional Diversity ◽  
Genetic Drift ◽  
Brown Trout ◽  
Balancing Selection

Supergene degeneration opposes polymorphism: The curious case of balanced lethals

2021 ◽  
Author(s):  
Emma Berdan ◽  
Alexandre Blanckaert ◽  
Roger K Butlin ◽  
Thomas Flatt ◽  
Tanja Slotte ◽  
...  
Keyword(s):  
Equilibrium State ◽  
Balancing Selection ◽  
Mutation Accumulation ◽  
Small Population ◽  
Quasi Equilibrium ◽  
Deleterious Mutations ◽  
Critical Factors ◽  
Critical Aspect ◽  
Allopatric Divergence

Supergenes offer some of the most spectacular examples of long-term balancing selection in nature but their origin and maintenance remain a mystery. A critical aspect of supergenes is reduced recombination between arrangements. Reduced recombination protects adaptive multi-trait phenotypes, but can also lead to degeneration through mutation accumulation. Mutation accumulation can stabilize the system through the emergence of associative overdominance (AOD), destabilize the system, or lead to new evolutionary outcomes. One such outcome is the formation of balanced lethal systems, a maladaptive system where both supergene arrangements have accumulated deleterious mutations to the extent that both homozygotes are inviable, leaving only heterozygotes to reproduce. Here, we perform a simulation study to understand the conditions under which these different outcomes occur, assuming a scenario of introgression after allopatric divergence. We found that AOD aids the invasion of a new supergene arrangement and the establishment of a polymorphism. However, this polymorphism is easily destabilized by further mutation accumulation. While degradation may strengthen AOD, thereby stabilizing the supergene polymorphism, it is often asymmetric, which is the key disrupter of the quasi-equilibrium state of the polymorphism. Furthermore, mechanisms that accelerate degeneration also tend to amplify asymmetric mutation accumulation between the supergene arrangements and vice versa. As the evolution of a balanced lethal system requires symmetric degradation of both arrangements, this leaves highly restricted conditions under which such a system could evolve. We show that small population size and low dominance coefficients are critical factors, as these reduce the efficacy of selection. The dichotomy between the persistence of a polymorphism and degradation of supergene arrangements likely underlies the rarity of balanced lethal systems in nature.

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