Does Sequence Conservation Provide Evidence for Biological Function?

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.

Keywords: dN/dS; gene transfer agents; phage domestication; prophage; purifying selection; selection for function; selfish gene.