Correlated evolution of nearby residues in Drosophilid proteins

Autor: Doris Bachtrog, Benjamin J. Callahan, Richard A. Neher, Peter Andolfatto, Boris I. Shraiman
Rok vydání: 2011
Předmět:
Zdroj: PLoS Genetics
PLoS Genetics, Vol 7, Iss 2, p e1001315 (2011)
DOI: 10.5451/unibas-ep53999
Popis: 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.
Author Summary Genes are templates for proteins, yet evolutionary studies of genes and proteins often bear little resemblance. Analyses of gene evolution typically treat each codon independently, quantifying gene evolution by summing over the constituent codons. In contrast, studies of protein evolution generally incorporate protein structure and interactions between amino acids explicitly. We investigate correlations in the evolution of codons as a function of their distance from each other along the protein coding sequence. This approach is motivated by the expectation that codons near each other in sequence often encode amino acids belonging to the same functional unit. Consequently, these amino acids are more likely to interact and/or experience similar selective regimes, introducing correlation between the evolution of the underlying codons. We find codon evolution in Drosophilids to be correlated over a characteristic length scale of ≈10 codons. Specifically, the presence of a non-synonymous substitution substantially increases the probability of further such substitutions nearby, particularly within that lineage. Further analysis suggests both functional interactions between amino acids and correlation in the strength of selection contribute to this effect. These findings are relevant for understanding the relative importance of different modes of selection, and particularly the role of epistasis, in gene and protein evolution.
Databáze: OpenAIRE
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