Mutation: Difference between revisions

{{cquote|Our theoretical findings indicate that mutator hitchhiking can set in motion a self-reinforcing loss of replication fidelity, but the question of how a process as robust as natural selection could allow this to happen remains. The key fact is that natural selection, although eminently robust, is a short-sighted process that favors traits with immediate fitness benefits. The fitness cost of mutator hitchhiking is generally not anticipated because of the slow accumulation of deleterious load. When a mutator hitchhikes with a new beneficial mutation, a simple model shows that the increased deleterious load due to the mutator is in fact suppressed during the spread of the beneficial mutation. Indeed, the full fitness cost of the mutator is only realized well after the beneficial mutation has stopped spreading (''SI Text''). A mutator may therefore enjoy the immediate benefit of producing a new beneficial mutation without anticipating the eventual increase in deleterious load. Because of this delay in the accumulation of deleterious load, natural selection can drive mutation rate up to the point of no return, where fM^mM^u² becomes the dominant term ([http://www.pnas.org/content/vol104/issue15/images/large/zpq0130757960004.jpeg Fig. 4A]); even if the increase in deleterious load is lethal, it is not anticipated ([http://www.pnas.org/content/vol104/issue15/images/large/zpq0130757960004.jpeg Fig. 4B]). At the population level, this failure to anticipate the establishment of a lethal deleterious load is partly due to the sharpness of the threshold separating lethal from viable mutation rates ([http://www.pnas.org/cgi/content/full/104/15/6266#B22 22, 24]), such that there is no slow fitness decrease to "warn" of impending extinction. <ref>[http://www.pnas.org/cgi/content/abstract/0607280104v1 ''Complete genetic linkage can subvert natural selection''] by Philip J. Gerrish, Alexandre Colato, Alan S. Perelson, and Paul D. Sniegowski, ''Proceedings of the National Academy of Sciences'' USA, published online before print April 3, 2007

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== References ==