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Edited* by Susan Lindquist, Whitehead Institute for Biomedical Research, Cambridge, MA, and approved December 9, 2010 (received for review August 30, 2010)
Abstract
Making genes into gene products is subject to predictable errors, each with a phenotypic effect that depends on a normally cryptic sequence. Many cryptic sequences have strongly deleterious effects, for example when they cause protein misfolding. Strongly deleterious effects can be avoided globally by avoiding making errors (e.g., via proofreading machinery) or locally by ensuring that each error has a relatively benign effect. The local solution requires powerful selection acting on every cryptic site and so evolves only in large populations. Small populations with less effective selection evolve global solutions. Here we show that for a large range of realistic intermediate population sizes, the evolutionary dynamics are bistable and either solution may result. The local solution facilitates the genetic assimilation of cryptic genetic variation and therefore substantially increases evolvability.
Footnotes
- 1To whom correspondence may be addressed. E-mail: rajon{at}email.arizona.edu or masel{at}u.arizona.edu.
Author contributions: E.R. and J.M. designed research; E.R. performed research; E.R. and J.M. analyzed data; and E.R. and J.M. wrote the paper.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1012918108/-/DCSupplemental.
Evolution of molecular error rates and the consequences for evolvability
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