Drift barriers to quality control when genes are expressed at different levels

Kun Xiong, Jay P. McEntee, David J. Porfirio, Joanna Masel

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Gene expression is imperfect, sometimes leading to toxic products. Solutions take two forms: globally reducing error rates, or ensuring that the consequences of erroneous expression are relatively harmless. The latter is optimal, but because it must evolve independently at so many loci, it is subject to a stringent “drift barrier”—a limit to how weak the effects of a deleterious mutation s can be, while still being effectively purged by selection, expressed in terms of the population size N of an idealized population such that purging requires s < -1/N. In previous work, only large populations evolved the optimal local solution, small populations instead evolved globally low error rates, and intermediate populations were bistable, with either solution possible. Here, we take into consideration the fact that the effectiveness of purging varies among loci, because of variation in gene expression level, and variation in the intrinsic vulnerabilities of different gene products to error. The previously found dichotomy between the two kinds of solution breaks down, replaced by a gradual transition as a function of population size. In the extreme case of a small enough population, selection fails to maintain even the global solution against deleterious mutations, explaining the nonmonotonic relationship between effective population size and transcriptional error rate that was recently observed in experiments on Escherichia coli, Caenorhabditis elegans, and Buchnera aphidicola.

Original languageEnglish (US)
Pages (from-to)397-407
Number of pages11
JournalGenetics
Volume205
Issue number1
DOIs
StatePublished - Jan 2017

Keywords

  • Cryptic genetic variation
  • Evolvability
  • Proofreading
  • Robustness
  • Stop codon readthrough
  • Transcriptional errors

ASJC Scopus subject areas

  • Genetics

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