title: Climbing mount probable: mutation as a cause of nonrandomness in evolution.
abstract: The classic view of evolution as "shifting gene frequencies" in the Modern Synthesis literally means that evolution is the modulation of existing variation ("standing variation"), as opposed to a "new mutations" view of evolution as a 2-step process of mutational origin followed by acceptance-or-rejection (via selection and drift). The latter view has received renewed attention, yet its implications for evolutionary causation still are not widely understood. We review theoretical results showing that this conception of evolution allows for a role of mutation as a cause of nonrandomness, a role that could be important but has been misconceived and associated misleadingly with neutral evolution. Specifically, biases in the introduction of variation, including mutational biases, may impose predictable biases on evolution, with no necessary dependence on neutrality. As an example of how important such effects may be, we present a new analysis partitioning the variance in mean rates of amino acid replacement during human-chimpanzee divergence to components of codon mutation and amino acid exchangeability. The results indicate that mutational effects are not merely important but account for most of the variance explained. The challenge that such results pose for comparative genomics is to address mutational effects as a necessary part of any analysis of causal factors. To meet this challenge requires developing knowledge of mutation as a biological process, understanding how mutation imposes propensities on evolution, and applying methods of analysis that incorporate mutational effects.
authors.affiliation: Center for Advanced Research in Biotechnology, Rockville, MD 20850, USA. stoltzfu@umbi.umd.edu
authors.forename: Arlin
authors.initials: A
authors.lastname: Stoltzfus
authors.forename: Lev Y
authors.initials: LY
authors.lastname: Yampolsky
mesh_terms: D019143:Evolution, Molecular; D040961:Genetic Drift; D014644:Genetic Variation; D005828:Genetics, Population; D008957:Models, Genetic; D009154:Mutation