Review
Heredity (2007) 99, 364–373; doi:10.1038/sj.hdy.6801031; published online 11 July 2007
Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level
A L Hughes1
1Department of Biological Sciences, University of South Carolina, Columbia, SC, USA
Correspondence: Dr AL Hughes, Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA. E-mail: austin@biol.sc.edu
Received 10 April 2007; Revised 4 June 2007; Accepted 6 June 2007; Published online 11 July 2007.
Abstract
Recent years have seen an explosion of interest in evidence for positive Darwinian selection at the molecular level. This quest has been hampered by the use of statistical methods that fail adequately to rule out alternative hypotheses, particularly the relaxation of purifying selection and the effects of population bottlenecks, during which the effectiveness of purifying selection is reduced. A further problem has been the assumption that positive selection will generally involve repeated amino-acid changes to a single protein. This model was derived from the case of the vertebrate major histocompatibility complex (MHC), but the MHC proteins are unusual in being involved in protein–protein recognition and in a co-evolutionary process of pathogens. There is no reason to suppose that repeated amino-acid changes to a single protein are involved in selectively advantageous phenotypes in general. Rather adaptive phenotypes are much more likely to result from other causes, including single amino-acid changes; deletion or silencing of genes or changes in the pattern of gene expression.
Keywords:
positive selection, nearly neutral theory, nucleotide substitution
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