A Test of Neutral Molecular Evolution Based on Nucleotide Data

Hudson, Richard R.; Kreitman, Martin; Aguadé, Montserrat

doi:10.1093/genetics/116.1.153

Cited by 1,556 publications

(215 citation statements)

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“…Figure 6 further suggests that the distribution of variants in the hypervariable region is incompatible with a neutral explanation. Only one previous study, that of Kreitman and others on Drosophila melanogaster Adh, has identified a similar peak of polymorphism (KREITMAN and AGUADE 1986;HUDSON et al 1987;KREITMAN and HUDSON 1991). As this peak flanks the amino acid polymorphism causing the electrophoretic difference between D. melanogaster Adh alleles, these authors have concluded that the amino acid polymorphism is subject to balancing selection.…”

Section: Variation In Intensities Of Purifying Selectionmentioning

confidence: 90%

“…For this reason we have sequenced the same region from a number of closely related species. This also provides both phylogenetic information and an interspecific comparison for future tests of selective neutrality (i.e., HUDSON et al 1987). Our sequence analysis of species related to A. thaliana includes C. arenosa, H. diffusa, C. bursa-pastoris, A .…”

Section: Figure 1-(a)mentioning

confidence: 99%

“…KREITMAN (1991) found that the TAJIMA test failed to reject neutrality at D . melanogaster Adh while a test incorporating inter-specific divergence at the locus (HUDSON et al 1987) detected a significant departure from neutrality. An additional reason for not placing too much emphasis on these test results is theoretical: the models on which the tests are based assume a Wright-Fisher distribution and this assumption is violated in the case of a global sample such as ours.…”

Section: Variation In Intensities Of Purifying Selectionmentioning

confidence: 99%

“…Because polymorphism studies were pioneered in Drosophila and Escherichia coli [e.g., LEWONTIN and HUBBY (1966) and MILKMAN (1973), respectively), nucleotide polymorphism studies of nuclear DNA have concentrated on these taxa. KRETIWW'S (1983) studies of alcohol dehydre genase (Adh) in Drosophila initiated this work and, with the introduction of statistical tools to distinguish between the actions of neutral and adaptive processes (HUDSON et aL 1987;MCDONALD and KRFJIWW 1991), his work has remained the standard (KRFSIUAN and HUDSON 1991).…”

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confidence: 99%

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Haplotypic divergence coupled with lack of diversity at the Arabidopsis thaliana alcohol dehydrogenase locus: roles for both balancing and directional selection?

et al. 1994

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We designate a region of the alcohol dehydrogenase locus (Adh) of the weedy crucifer, Arabidopsis thaliana, as "hypervariable" on the basis of a comparison of sequences from ecotypes Columbia and Landsberg. We found eight synonymous and two replacement mutations in the first 262 nucleotides of exon 4, and an additional two mutations in the contiguous region of intron 3. The rest of the sequence (2611 bp) has just three mutations, all of them confined to noncoding regions. Our survey of the hypervariable region among 37 ecotypes of A. thaliana revealed two predominant haplotypes, corresponding to the Columbia and Landsberg sequences. We identified five additional haplotypes and 4 additional segregating sites. The lack of haplotype diversity is presumably in part a function of low rates of recombination between haplotypes conferred by A. thaliana's tendency to self-fertilize. However, an analysis in 32 ecotypes of 12 genome-wide polymorphic markers distinguishing Columbia and Landsberg ecotypes indicated levels of outcrossing sufficient at least to erode linkage disequilibrium between dispersed markers. We discuss possible evolutionary explanations for the coupled observation of marked divergence within the hypervariable region and a lack of haplotype diversity among ecotypes. The sequence of the region for closely related species argues against the possibility that one allele is the product of introgression. We note (1) that several loss of function mutations (both naturally and chemically induced) map to the hypervariable region, and (2) the presence of two amino acid replacement polymorphisms, one of which causes the mobility difference between the two major classes of A. thaliana Adh electrophoretic alleles. We argue that protein polymorphism in such a functionally significant part of the molecule may be subject to balancing selection. The observed pattern of extensive divergence between the alleles is consistent with this explanation because balancing selection on a particular site maintains linked neutral polymorphisms at intermediate frequencies.

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Section: Variation In Intensities Of Purifying Selectionmentioning

confidence: 90%

Section: Figure 1-(a)mentioning

confidence: 99%

Section: Variation In Intensities Of Purifying Selectionmentioning

confidence: 99%

mentioning

confidence: 99%

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Haplotypic divergence coupled with lack of diversity at the Arabidopsis thaliana alcohol dehydrogenase locus: roles for both balancing and directional selection?

et al. 1994

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“…2020). For example, presence of balancing (i.e., diversifying) selection at the Adh locus in Drosophila was discovered by an excess of nucleotide polymorphisms in the coding region relative to the 5’-flanking sequences (HKA test) (Hudson et al . 1987).…”

Section: Introductionmentioning

confidence: 99%

Following the Trail of One Million Genomes: Footprints of SARS-CoV-2 Adaptation to Humans

Akther

Bezrucenkovas

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accumulated genomic mutations at an approximately linear rate since it first infected human populations in late 2019. Controversies remain regarding the identity, proportion, and effects of adaptive mutations as SARS-CoV-2 evolves from a bat- to a human-adapted virus. The potential for vaccine-escape mutations poses additional challenges in pandemic control. Despite being of great interest to therapeutic and vaccine development, human-adaptive mutations in SARS-CoV-2 are masked by a genome-wide linkage disequilibrium under which neutral and even deleterious mutations can reach fixation by chance or through hitchhiking. Furthermore, genome-wide linkage equilibrium imposes clonal interference by which multiple adaptive mutations compete against one another. Informed by insights from microbial experimental evolution, we analyzed close to one million SARS-CoV-2 genomes sequenced during the first year of the COVID-19 pandemic and identified putative human-adaptive mutations according to the rates of synonymous and missense mutations, temporal linkage, and mutation recurrence. Furthermore, we developed a forward-evolution simulator with the realistic SARS-CoV-2 genome structure and base substitution probabilities able to predict viral genome diversity under neutral, background selection, and adaptive evolutionary models. We conclude that adaptive mutations have emerged early, rapidly, and constantly to dominate SARS-CoV-2 populations despite clonal interference and purifying selection. Our analysis underscores a need for genomic surveillance of mutation trajectories at the local level for early detection of adaptive and immune-escape variants. Putative human-adaptive mutations are over-represented in viral proteins interfering host immunity and binding host-cell receptors and thus may serve as priority targets for designing therapeutics and vaccines against human-adapted forms of SARS-CoV-2.

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Evolutionary adaptations of gene structure and expression in natural populations in relation to a changing environment: A multidisciplinary approach to address the million-year saga of a small fish

1998

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A Test of Neutral Molecular Evolution Based on Nucleotide Data

Cited by 1,556 publications

References 15 publications

Haplotypic divergence coupled with lack of diversity at the Arabidopsis thaliana alcohol dehydrogenase locus: roles for both balancing and directional selection?

Haplotypic divergence coupled with lack of diversity at the Arabidopsis thaliana alcohol dehydrogenase locus: roles for both balancing and directional selection?

Following the Trail of One Million Genomes: Footprints of SARS-CoV-2 Adaptation to Humans

Evolutionary adaptations of gene structure and expression in natural populations in relation to a changing environment: A multidisciplinary approach to address the million-year saga of a small fish

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