Does Sequence Conservation Provide Evidence for Biological Function?. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Omer, Seila; Harlow, Timothy J.; Gogarten, Johann Peter
• Is Part Of: Trends in microbiology. Volume 25:Issue 1(2017)
• Page Start: 11
• Page End: 18
• Publication Date: 2017-01
• Subjects: purifying selection -- prophage -- phage domestication -- gene transfer agents -- selection for function -- dN/dS -- selfish gene; Microbiology -- Periodicals; Infection -- Periodicals; Virulence (Microbiology) -- Periodicals; Infection -- Periodicals; Microbiology -- Periodicals; Virulence -- Periodicals; Microbiologie -- Périodiques; Infection -- Périodiques; Virulence (Microbiologie) -- Périodiques; Infection; Microbiology; Virulence (Microbiology); 579
• DOI: 10.1016/j.tim.2016.09.010
• Languages: English
• ISSNs: 0966-842X

Abstract

Abstract : Finding a signature of purifying selection in a gene is usually interpreted as evidence for the gene providing a function that is targeted by natural selection. This opinion offers a very different hypothesis: purifying selection may be due to removing harmful mutations from the population, that is, the gene and its encoded protein become harmful after a mutation occurred, possibly because the mutated protein interferes with the translation machinery, or because of toxicity of the misfolded protein. Finding a signature of purifying selection should not automatically be considered proof of the gene's selectable function. Trends: The current accepted definitions of biological function for a gene assume an evolutionary history shaped by natural selection. This assumption is based on the observation that most genes, characterized genotypically and phenotypically, display in their DNA sequence a considerable excess of synonymous substitutions over what would be expected, if the substitution process were random. Many genes potentially detrimental for bacterial fitness, lacking functionally relevant expression, share a common evolutionary record with their host organisms through vertical descent. Their DNA sequences present the same type of selective footprints found in neighboring functional genes. The observation that natural selection operates on both functional and putative nonfunctional genes challenges the default connection between sequence conservation and biological function.