scholarly journals On the relative roles of background selection and genetic hitchhiking in shaping human cytomegalovirus genetic diversity

2015 ◽  
Vol 25 (1) ◽  
pp. 403-413 ◽  
Author(s):  
Nicholas Renzette ◽  
Timothy F. Kowalik ◽  
Jeffrey D. Jensen
Keyword(s):  
Genetic Diversity ◽  
Human Cytomegalovirus ◽  
Background Selection ◽  
Genetic Hitchhiking

scholarly journals Statistical Tests of Neutrality of Mutations Against Population Growth, Hitchhiking and Background Selection

Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 915-925 ◽  
Author(s):  
Yun-Xin Fu
Keyword(s):  
Population Growth ◽  
Statistical Tests ◽  
Dna Polymorphisms ◽  
Background Selection ◽  
Genetic Hitchhiking ◽  
Alternative Models ◽  
Tests Of Neutrality ◽  
Rare Alleles

The main purpose of this article is to present several new statistical tests of neutrality of mutations against a class of alternative models, under which DNA polymorphisms tend to exhibit excesses of rare alleles or young mutations. Another purpose is to study the powers of existing and newly developed tests and to examine the detailed pattern of polymorphisms under population growth, genetic hitchhiking and background selection. It is found that the polymorphic patterns in a DNA sample under logistic population growth and genetic hitchhiking are very similar and that one of the newly developed tests, FS, is considerably more powerful than existing tests for rejecting the hypothesis of neutrality of mutations. Background selection gives rise to quite different polymorphic patterns than does logistic population growth or genetic hitchhiking, although all of them show excesses of rare alleles or young mutations. We show that Fu and Li's tests are among the most powerful tests against background selection. Implications of these results are discussed.

scholarly journals Hitchhiker’s guide to genetic diversity in socially structured populations

2012 ◽  
Vol 58 (2) ◽  
pp. 287-297 ◽  
Author(s):  
L. S. Premo
Keyword(s):  
Genetic Diversity ◽  
Mitochondrial Dna ◽  
Critical Review ◽  
Structured Populations ◽  
Genetic Hitchhiking ◽  
Gene Substitution ◽  
Dna Diversity ◽  
Low Levels ◽  
Cultural Traits

Abstract When selection increases the frequency of a beneficial gene substitution it can also increase the frequencies of linked neutral alleles through a process called genetic hitchhiking. A model built to investigate reduced genetic diversity in Pleistocene hominins shows that genetic hitchhiking can have a strong effect on neutral diversity in the presence of culturally mediated migration. Under conditions in which genetic and cultural variants are transmitted symmetrically, neutral genes may also hitchhike to higher frequencies on the coattails of adaptive cultural traits through a process called cultural hitchhiking. Cultural hitchhiking has been proposed to explain why some species of matrilineal whales display relatively low levels of mitochondrial DNA diversity, and it may be applicable to humans as well. This paper provides a critical review of recent models of both types of hitchhiking in socially structured populations. The models’ assumptions and predictions are compared and discussed in the hope that studies of reduced genetic diversity in humans might improve our understanding of reduced genetic diversity in other species, and vice versa [Current Zoology 58 (1): 287–297, 2012].

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 Mating System Differences on Nucleotide Diversity at the Phosphoglucose Isomerase Locus in the Plant Genus Leavenworthia

Genetics ◽  
1999 ◽  
Vol 151 (1) ◽  
pp. 343-357 ◽  
Author(s):  
F Liu ◽  
D Charlesworth ◽  
M Kreitman
Keyword(s):  
Genetic Diversity ◽  
Nucleotide Diversity ◽  
Phosphoglucose Isomerase ◽  
Self Incompatibility ◽  
Background Selection ◽  
Selective Sweeps ◽  
Balanced Polymorphism ◽  
Neutral Genetic Diversity ◽  
Low Diversity ◽  
High Diversity

AbstractTo test the theoretical prediction that highly inbreeding populations should have low neutral genetic diversity relative to closely related outcrossing populations, we sequenced portions of the cytosolic phosphoglucose isomerase (PgiC) gene in the plant genus Leavenworthia, which includes both self-incompatible and inbreeding taxa. On the basis of sequences of intron 12 of this gene, the expected low diversity was seen in both populations of the selfers Leavenworthia uniflora and L. torulosa and in three highly inbreeding populations of L. crassa, while high diversity was found in self-incompatible L. stylosa, and moderate diversity in L. crassa populations with partial or complete self-incompatibility. In L. stylosa, the nucleotide diversity was strongly structured into three haplotypic classes, differing by several insertion/deletion sequences, with linkage disequilibrium between sequences of the three types in intron 12, but not in the adjacent regions. Differences between the three kinds of haplotypes are larger than between sequences of this gene region from different species. The haplotype divergence suggests the presence of a balanced polymorphism at this locus, possibly predating the split between L. stylosa and its two inbreeding sister taxa, L. uniflora and L. torulosa. It is therefore difficult to distinguish between different potential causes of the much lower sequence diversity at this locus in inbreeding than outcrossing populations. Selective sweeps during the evolution of these populations are possible, or background selection, or merely loss of a balanced polymorphism maintained by overdominance in the populations that evolved high selfing rates.

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 The pattern of neutral molecular variation under the background selection model.

Genetics ◽  
1995 ◽  
Vol 141 (4) ◽  
pp. 1619-1632 ◽  
Author(s):  
D Charlesworth ◽  
B Charlesworth ◽  
M T Morgan
Keyword(s):  
Genetic Diversity ◽  
Genomic Region ◽  
Stochastic Simulations ◽  
Background Selection ◽  
Effective Population ◽  
Frequency Spectra ◽  
Low Genetic Diversity ◽  
Neutral Locus ◽  
Large Populations ◽  
Site Diversity

Abstract Stochastic simulations of the infinite sites model were used to study the behavior of genetic diversity at a neutral locus in a genomic region without recombination, but subject to selection against deleterious alleles maintained by recurrent mutation (background selection). In large populations, the effect of background selection on the number of segregating sites approaches the effect on nucleotide site diversity, i.e., the reduction in genetic variability caused by background selection resembles that caused by a simple reduction in effective population size. We examined, by coalescence-based methods, the power of several tests for the departure from neutral expectation of the frequency spectra of alleles in samples from randomly mating populations (Tajima's, Fu and Li's, and Watterson's tests). All of the tests have low power unless the selection against mutant alleles is extremely weak. In Drosophila, significant Tajima's tests are usually not obtained with empirical data sets from loci in genomic regions with restricted recombination frequencies and that exhibit low genetic diversity. This is consistent with the operation of background selection as opposed to selective sweeps. It remains to be decided whether background selection is sufficient to explain the observed extent of reduction in diversity in regions of restricted recombination.

scholarly journals The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations

1997 ◽  
Vol 70 (2) ◽  
pp. 155-174 ◽  
Author(s):  
BRIAN CHARLESWORTH ◽  
MAGNUS NORDBORG ◽  
DEBORAH CHARLESWORTH
Keyword(s):  
Genetic Diversity ◽  
Linkage Disequilibrium ◽  
Balancing Selection ◽  
Polymorphic Locus ◽  
Stochastic Simulations ◽  
Population Subdivision ◽  
Background Selection ◽  
Balanced Polymorphism ◽  
Local Selection ◽  
Species Population

Levels of neutral genetic diversity in populations subdivided into two demes were studied by multi-locus stochastic simulations. The model includes deleterious mutations at loci throughout the genome, causing ‘background selection’, as well as a single locus at which a polymorphism is maintained, either by frequency-dependent selection or by local selective differences. These balanced polymorphisms induce long coalescence times at linked neutral loci, so that sequence diversity at these loci is enhanced at statistical equilibrium. We study how equilibrium neutral diversity levels are affected by the degree of population subdivision, the presence or absence of background selection, and the level of inbreeding of the population. The simulation results are compared with approximate analytical formulae, assuming the infinite sites neutral model. We discuss how balancing selection can be distinguished from local selection, by determining whether peaks of diversity in the region of the polymorphic locus are seen within or between demes. The width of such diversity peaks is shown to depend on the total species population size, rather than local deme sizes. We show that, with population subdivision, local selection enhances between-deme diversity even at neutral sites distant from the polymorphic locus, producing higher FST values than with no selection; very high values can be generated at sites close to a selected locus. Background selection also increases FST, mainly because of decreased diversity within populations, which implies that its effects may be distinguishable from those of local selection. Both effects are stronger in selfing than outcrossing populations. Linkage disequilibrium between neutral sites is generated by both balancing and local selection, especially in selfing populations, because of linkage disequilibrium between the neutral sites and the selectively maintained alleles. We discuss how these theoretical results can be related to data on genetic diversity within and between local populations of a species.

scholarly journals Background selection and patterns of genetic diversity in Drosophila melanogaster

1996 ◽  
Vol 68 (2) ◽  
pp. 131-149 ◽  
Author(s):  
Brian Charlesworth
Keyword(s):  
Genetic Diversity ◽  
Drosophila Melanogaster ◽  
Genetic Variability ◽  
Chromosomal Location ◽  
Theoretical Models ◽  
Distal Portion ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Chromosome 4 ◽  
Selective Forces

SummaryTheoretical models of the effects of selection against deleterious mutations on variation at linked neutral sites (background selection) are used to predict the relations between chromosomal location and genetic variability at the DNA level, in Drosophila melanogaster. The sensitivity of the predictions to variation in the mutation, selection and recombination parameters on which they are based is examined. It is shown that many features of the observed relations between chromosomal location and level of genetic diversity in D. melanogaster can be explained by background selection, especially if the weak selective forces acting on transposable elements are taken into account. In particular, the gradient in diversity in the distal portion of the X chromosome, and the lack of diversity on chromosome 4 and at the bases of the major chromosomes, can be fully accounted for. There are, however, discrepancies between predicted and observed values for some loci in D. melanogaster, which may reflect the effects of forces other than background selection.

scholarly journals Human Cytomegalovirus Intrahost Evolution--A New Avenue for Understanding and Controlling Herpesvirus Infections

2014 ◽  
Author(s):  
Nicholas Renzette ◽  
Laura Gibson ◽  
Jeffrey D. Jensen ◽  
Timothy F. Kowalik
Keyword(s):  
Genetic Diversity ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Spatiotemporal Evolution ◽  
Human Host ◽  
New Information ◽  
Long Timescales ◽  
Shed Light

Human cytomegalovirus (HCMV) is exquisitely adapted to the human host, and much research has focused on its evolution over long timescales spanning millennia. Here, we review recent data exploring the evolution of the virus on much shorter timescales, on the order of days or months. We describe the intrahost genetic diversity of the virus isolated from humans, and how this diversity contributes to HCMV spatiotemporal evolution. We propose mechanisms to explain the high levels of intrahost diversity and discuss how this new information may shed light on HCMV infection and pathogenesis.

scholarly journals A New Model of Genetic Variation and Evolution Evaluates Relative Impacts of Background Selections and Selective Sweeps

2020 ◽  
Author(s):  
Xun Gu
Keyword(s):  
Genetic Diversity ◽  
Genetic Variation ◽  
Neutral Theory ◽  
Population Diversity ◽  
Simple Relationship ◽  
Small Contribution ◽  
Background Selection ◽  
Selective Sweeps ◽  
Recombination Rates ◽  
The One

AbstractIntra-population genetic variation and interspecies divergence in chromosome regions can be considerably affected by different local recombination rates. There are two models: (i) the selective sweeps that reduces the genetic diversity at linked sites and elevates the divergence rate; and (ii) the background selection that reduces the genetic diversity at linked sites and divergence rate. An intriguing question, yet highly controversial, is which one is dominant. In this paper, I develop a framework of generalize background selection, formulated by a diffusion model with two killing functions: the one associated with (negative) background selection is the rate to stop a fixation process of a mutation randomly, and the other associated with positive background selection (selective sweep) is the rate to stop a loss process of a mutation randomly. A simple relationship between the level of reduced diversity and the rate of divergence is derived, depending on the strength of generalized background selection (G) and the proportion of positive background selection (β). We analyzed the interspecies divergence and intra-population diversity in low-recombination regions of three organisms (fruitfly, soybean and human). Strikingly, all datasets demonstrated the dominance of (negative) background selection, and the positive background selection (selective sweeps) only has a small contribution (β∼10%). However, our analysis rejects the notion of β=0, namely, a complete negative background selection is unlikely. These findings may shed some lights on the long-term debates around Neutral Theory.

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