Fitting background-selection predictions to levels of nucleotide variation and divergence along the human autosomes

The controversy on the relative importance of background selection (BGS; against deleterious mutations) and genetic hitchhiking (associated with positive directional selection) in explaining patterns of nucleotide variation in natural populations stimulated research activities for almost a decade. Despite efforts from many theorists and empiricists, fundamental questions are still open, in particular, for the population genetics of regions of reduced recombination. On the other hand, the development of the BGS and hitchhiking models and the long struggle to distinguish them, all of which seem to be a purely academic exercise, led to quite practical advances that are useful for the identification of genes involved in adaptation and domestication.

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Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome

PLoS Genetics ◽

10.1371/journal.pgen.1004434 ◽

2014 ◽

Vol 10 (6) ◽

pp. e1004434 ◽

Cited By ~ 85

Author(s):

Josep M. Comeron

Keyword(s):

Drosophila Genome ◽

Nucleotide Variation ◽

Background Selection

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Balancing Selection on Electrophoretic Variation of Phosphoglucose Isomerase in Two Species of Field Cricket: Gryllus veletis and G. pennsylvanicus

Genetics ◽

10.1093/genetics/147.2.609 ◽

1997 ◽

Vol 147 (2) ◽

pp. 609-621

Author(s):

Laura A Katz ◽

Richard G Harrison

Keyword(s):

Balancing Selection ◽

Emergent Property ◽

Phosphoglucose Isomerase ◽

Field Cricket ◽

Nucleotide Variation ◽

Eastern United States ◽

Electrophoretic Variation ◽

Sympatric Populations ◽

Field Crickets ◽

Gryllus Veletis

Two species of crickets, Gryllus veletis and G. pennsylvanicus, share six electrophoretic mobility classes for the enzyme phosphoglucose isomerase (PGI), despite evidence from other genetic markers that the two species are not closely related within eastern North American field crickets. Moreover, the frequencies of the two most common PGI electrophoretic classes (PGI-100 and PGI-65) covary in sympatric populations of these species in the eastern United States, suggesting that PGI may be subject to trans-specific balancing selection. To determine the molecular basis of the electrophoretic variation, we characterized the DNA sequence of the Pgi gene from 29 crickets (15 G. veletis and 14 G. pennsylvanicus). Amino acid substitutions that distinguish the electrophoretic classes are not the same in the two species, and there is no evidence that specific replacement substitutions represent trans-specific polymorphism. In particular, the amino acids that diagnose the PGI-65 allele relative to the PGI-100 allele differ both between G. veletis and G. pennsylvanicus and within G. pennsylvanicus. The heterogeneity among electrophoretic classes that covary in sympatric populations coupled with analysis of patterns of nucleotide variation suggest that Pgi is not evolving neutrally. Instead, the data are consistent with balancing selection operating on an emergent property of the PGI protein.

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Sensitive analysis of single nucleotide variation by Cas13d orthologs, EsCas13d and RspCas13d

Biotechnology and Bioengineering ◽

10.1002/bit.27813 ◽

2021 ◽

Author(s):

Xin Qiao ◽

Yanmin Gao ◽

Jiaojiao Li ◽

Zhaoguan Wang ◽

Hongyan Qiao ◽

...

Keyword(s):

Nucleotide Variation ◽

Single Nucleotide Variation ◽

Single Nucleotide ◽

Sensitive Analysis

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Large-Scale Adaptive Hitchhiking Upon High Recombination inDrosophila simulans

Genetics ◽

10.1093/genetics/165.2.895 ◽

2003 ◽

Vol 165 (2) ◽

pp. 895-900 ◽

Cited By ~ 10

Author(s):

Humberto Quesada ◽

Ursula E M Ramírez ◽

Julio Rozas ◽

Montserrat Aguadé

Keyword(s):

Genetic Linkage ◽

Large Scale ◽

Intermediate Frequency ◽

Core Region ◽

Adaptive Mutation ◽

Nucleotide Variation ◽

Extended Haplotype ◽

Major Haplotype ◽

Pattern Of Variation

AbstractNatural selection is expected to leave a characteristic footprint on neighboring nucleotide variation through the effects of genetic linkage. The size of the region affected is proportional to the strength of selection and greatly reduced with the recombinational distance from the selected site. Thus, the genomic footprint of selection is generally believed to be restricted to a small DNA stretch in normal and highly recombining regions. Here, we study the effect of selection on linked polymorphism (hitchhiking effect) by surveying nucleotide variation across a highly recombining ∼88-kb genomic fragment in an African population of Drosophila simulans. We find a core region of up to 38 kb with a major haplotype at intermediate frequency. The extended haplotype structure that gradually vanishes until disappearing is unusual for a highly recombining region. Both the presence in the structured genomic domain of a single major haplotype depleted of variability and the detected spatial pattern of variation along the ∼88-kb fragment are incompatible with neutral predictions in a panmictic population. A major role of demographic effects could also be discarded. The observed pattern of variation clearly provides evidence that directional selection has acted recently on this region, sweeping out variation around a strongly adaptive mutation. Our findings suggest a major role of positive selection in shaping DNA variability even in highly recombining regions.

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Chromosomal Patterns of Microsatellite Variability Contrast Sharply in African and Non-African Populations of Drosophila melanogaster

Genetics ◽

10.1093/genetics/160.1.247 ◽

2002 ◽

Vol 160 (1) ◽

pp. 247-256

Author(s):

M Kauer ◽

B Zangerl ◽

D Dieringer ◽

C Schlötterer

Keyword(s):

Chromosomal Polymorphism ◽

Background Selection ◽

Selective Sweeps ◽

X Chromosomes ◽

Evolutionary Forces ◽

Relative Contribution ◽

African Populations ◽

Neutral Variation ◽

Colonization Process ◽

The Subject

Abstract Levels of neutral variation are influenced by background selection and hitchhiking. The relative contribution of these evolutionary forces to the distribution of neutral variation is still the subject of ongoing debates. Using 133 microsatellites, we determined levels of variability on X chromosomes and autosomes in African and non-African D. melanogaster populations. In the ancestral African populations microsatellite variability was higher on X chromosomes than on autosomes. In non-African populations X-linked polymorphism is significantly more reduced than autosomal variation. In non-African populations we observed a significant positive correlation between X chromosomal polymorphism and recombination rate. These results are consistent with the interpretation that background selection shapes levels of neutral variability in the ancestral populations, while the pattern in derived populations is determined by multiple selective sweeps during the colonization process. Further research, however, is required to investigate the influence of inversion polymorphisms and unequal sex ratios.

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

Genetics ◽

10.1093/genetics/147.2.915 ◽

1997 ◽

Vol 147 (2) ◽

pp. 915-925 ◽

Cited By ~ 294

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.

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Microsatellite Variation and Recombination Rate in the Human Genome

Genetics ◽

10.1093/genetics/156.3.1285 ◽

2000 ◽

Vol 156 (3) ◽

pp. 1285-1298 ◽

Cited By ~ 3

Author(s):

Bret A Payseur ◽

Michael W Nachman

Keyword(s):

Recombination Rate ◽

Microsatellite Polymorphism ◽

Published Data ◽

Strong Positive Correlation ◽

Background Selection ◽

Recombination Rates ◽

Microsatellite Variation ◽

Positive Correlation ◽

Genome Recombination ◽

Neutral Mutations

Abstract Background (purifying) selection on deleterious mutations is expected to remove linked neutral mutations from a population, resulting in a positive correlation between recombination rate and levels of neutral genetic variation, even for markers with high mutation rates. We tested this prediction of the background selection model by comparing recombination rate and levels of microsatellite polymorphism in humans. Published data for 28 unrelated Europeans were used to estimate microsatellite polymorphism (number of alleles, heterozygosity, and variance in allele size) for loci throughout the genome. Recombination rates were estimated from comparisons of genetic and physical maps. First, we analyzed 61 loci from chromosome 22, using the complete sequence of this chromosome to provide exact physical locations. These 61 microsatellites showed no correlation between levels of variation and recombination rate. We then used radiation-hybrid and cytogenetic maps to calculate recombination rates throughout the genome. Recombination rates varied by more than one order of magnitude, and most chromosomes showed significant suppression of recombination near the centromere. Genome-wide analyses provided no evidence for a strong positive correlation between recombination rate and polymorphism, although analyses of loci with at least 20 repeats suggested a weak positive correlation. Comparisons of microsatellites in lowest-recombination and highest-recombination regions also revealed no difference in levels of polymorphism. Together, these results indicate that background selection is not a major determinant of microsatellite variation in humans.

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Selection on X-linked Genes During Speciation in the Drosophila athabasca Complex

Genetics ◽

10.1093/genetics/144.2.689 ◽

1996 ◽

Vol 144 (2) ◽

pp. 689-703 ◽

Cited By ~ 1

Author(s):

Michael J Ford ◽

Charles F Aquadro

Keyword(s):

Computer Simulation ◽

Natural Selection ◽

Molecular Evolution ◽

Restriction Site ◽

Neutral Model ◽

Background Selection ◽

Selective Sweeps ◽

Differential Migration ◽

Site Survey ◽

Low Levels

Abstract We present the results of a restriction site survey of variation at five loci in Drosophila athabasca, complimenting a previous study of the period locus. There is considerably greater differentiation between the three semispecies of D. athabasca at the period locus and two other X-linked genes (neon-transient-A and E74A) than at three autosomal genes (Xdh, Adh and RC98). Using a modification of the HKA test, which uses fixed differences between the semispecies and a test based on differences in Fst among loci, we show that the greater differentiation of the X-linked loci compared with the autosomal loci is inconsistent with a neutral model of molecular evolution. We explore several evolutionary scenarios by computer simulation, including differential migration of X and autosomal genes, very low levels of migration among the semispecies, selective sweeps, and background selection, and conclude that X-linked selective sweeps in at least two of the semispecies are the best explanation for the data. This evidence that natural selection acted on the X-chromosome suggests that another X-linked trait, mating song differences among the semispecies, may have been the target of selection.

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