ArticlePLoS genetics2011
Correlated evolution of nearby residues in Drosophilid proteins.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
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- Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics.PLoS computational biology · 2024Article
- The Effect of Developmental Pleiotropy on the Evolution of Insect Immune Genes.Genome biology and evolution · 2023Article
- RETRACTED: Constraints on the evolution of toxin-resistant Na,K-ATPases have limited dependence on sequence divergence.PLoS genetics · 2022Article
- Local fitness and epistatic effects lead to distinct patterns of linkage disequilibrium in protein-coding genes.Genetics · 2022Article
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- Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing.eLife · 2021Article
- Episodic evolution of coadapted sets of amino acid sites in mitochondrial proteins.PLoS genetics · 2021Article
- Identifying the drivers of computationally detected correlated evolution among sites under antibiotic selection.Evolutionary applications · 2020Article
- Fine-Scale Haplotype Structure Reveals Strong Signatures of Positive Selection in a Recombining Bacterial Pathogen.Molecular biology and evolution · 2020Article
- Crossing fitness valleys via double substitutions within codons.BMC biology · 2019Article
- Selection on the mitochondrial ATP synthase 6 and the NADH dehydrogenase 2 genes in hares (Lepus capensis L., 1758) from a steep ecological gradient in North Africa.BMC evolutionary biology · 2017Article
- Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans.PLoS genetics · 2016Article
- A Genomic Map of the Effects of Linked Selection in Drosophila.PLoS genetics · 2016Article
- Changing preferences: deformation of single position amino acid fitness landscapes and evolution of proteins.Biology letters · 2015Review
- The effects of natural selection across molecular pathways in Drosophila melanogaster.BMC evolutionary biology · 2015Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here we investigate the correlations between coding sequence substitutions as a function of their separation along the protein sequence. We consider both substitutions between the reference genomes of several Drosophilids as well as polymorphisms in a population sample of Zimbabwean Drosophila melanogaster. We find that amino acid substitutions are "clustered" along the protein sequence, that is, the frequency of additional substitutions is strongly enhanced within ≈10 residues of a first such substitution. No such clustering is observed for synonymous substitutions, supporting a "correlation length" associated with selection on proteins as the causative mechanism. Clustering is stronger between substitutions that arose in the same lineage than it is between substitutions that arose in different lineages. We consider several possible origins of clustering, concluding that epistasis (interactions between amino acids within a protein that affect function) and positional heterogeneity in the strength of purifying selection are primarily responsible. The role of epistasis is directly supported by the tendency of nearby substitutions that arose on the same lineage to preserve the total charge of the residues within the correlation length and by the preferential cosegregation of neighboring derived alleles in our population sample. We interpret the observed length scale of clustering as a statistical reflection of the functional locality (or modularity) of proteins: amino acids that are near each other on the protein backbone are more likely to contribute to, and collaborate toward, a common subfunction.
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