Evolutionary Fingerprinting of Genes

Item Type Journal Article
Author Sergei L Kosakovsky Pond
Author Konrad Scheffler
Author Michael B Gravenor
Author Art F Y Poon
Author Simon D W Frost
URL http://www.ncbi.nlm.nih.gov/pubmed/19864470
Publication Molecular Biology and Evolution
ISSN 1537-1719
Date Oct 28, 2009
Extra PMID: 19864470
Journal Abbr Mol. Biol. Evol
DOI 10.1093/molbev/msp260
Accessed 2009-12-30 14:22:35
Library Catalog NCBI PubMed
Abstract Over time, natural selection molds every gene into a unique mosaic of sites evolving rapidly or resisting change - an 'evolutionary fingerprint' of the gene. Aspects of this evolutionary fingerprint, such as the site-specific ratio of nonsynonymous to synonymous substitution rates (dN/dS), are commonly used to identify genetic features of potential biological interest; however, no framework exists for comparing evolutionary fingerprints between genes. We hypothesize that protein coding genes with similar protein structure and/or function tend to have similar evolutionary fingerprints, and that comparing evolutionary fingerprints can be useful for discovering similarities between genes in a way that is analogous to, but independent of, discovery of similarity via sequence-based comparison tools such as BLAST. To test this hypothesis, we develop a novel model of coding sequence evolution that uses a general bivariate discrete parameterization of the evolutionary rates. We show that this approach provides a better fit to the data using a smaller number of parameters than existing models. Next, we use the model to represent evolutionary fingerprints as probability distributions and present a methodology for comparing these distributions in a way that is robust against variations in data set size and divergence. Finally, using sequences of three rapidly evolving RNA viruses (HIV-1, Hepatitis C virus and Influenza A virus) we demonstrate that genes within the same functional group tend to have similar evolutionary fingerprints. Our framework provides a sound statistical foundation for efficient inference and comparison of evolutionary rate patterns in arbitrary collections of gene alignments, clustering homologous and non-homologous genes and investigation of biological and functional correlates of evolutionary rates.
Title Evolutionary Fingerprinting of Genes
Date Added 2009-12-30 09:22
Date Modified 2009-12-30 09:22