TY - JOUR
T1 - A model of compensatory molecular evolution involving multiple sites in RNA molecules
AU - Kusumi, Junko
AU - Ichinose, Motoshi
AU - Takefu, Masasuke
AU - Piskol, Robert
AU - Stephan, Wolfgang
AU - Iizuka, Masaru
N1 - Funding Information:
We thank G. Bazykin and two anonymous reviewers for comments on an earlier version of the manuscript. This work was partially supported by Grants-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (Grant no. 25400139 and 25400143 to MI) and the Deutsche Forschungsgemeinschaft (Grant no. STE 325/ 8-1 to WS).
PY - 2016/1/7
Y1 - 2016/1/7
N2 - Consider two sites under compensatory fitness interaction, such as a Watson-Crick base pair in an RNA helix or two interacting residues in a protein. A mutation at any one of these two sites may reduce the fitness of an individual. However, fitness may be restored by the occurrence of a second mutation at the other site. Kimura modeled this process using a two-locus haploid fitness scheme with two alleles at each locus. He predicted that compensatory evolution following this model is very rare unless selection against the deleterious single mutations is weak and linkage between the interacting sites is tight. Here we investigate the question whether the rate of compensatory evolution increases if we take the context of the two directly interacting sites into account. By "context", we mean the effect of neighboring sites in an RNA helix. Interaction between the focal pair of sites under consideration and the context may lead to so-called indirect compensation. Thus, extending Kimura's classical model of compensatory evolution, we study the effects of both direct and indirect compensation on the rate of compensatory evolution. It is shown that the effects of indirect compensation are very strong. We find that recombination does not slow down the rate of compensatory evolution as predicted by the classical model. Instead, compensatory substitutions may be relatively frequent, even if linkage between the focal interacting sites is loose, selection against deleterious mutations is strong, and mutation rate is low. We compare our theoretical results with data on RNA secondary structures from vertebrate introns.
AB - Consider two sites under compensatory fitness interaction, such as a Watson-Crick base pair in an RNA helix or two interacting residues in a protein. A mutation at any one of these two sites may reduce the fitness of an individual. However, fitness may be restored by the occurrence of a second mutation at the other site. Kimura modeled this process using a two-locus haploid fitness scheme with two alleles at each locus. He predicted that compensatory evolution following this model is very rare unless selection against the deleterious single mutations is weak and linkage between the interacting sites is tight. Here we investigate the question whether the rate of compensatory evolution increases if we take the context of the two directly interacting sites into account. By "context", we mean the effect of neighboring sites in an RNA helix. Interaction between the focal pair of sites under consideration and the context may lead to so-called indirect compensation. Thus, extending Kimura's classical model of compensatory evolution, we study the effects of both direct and indirect compensation on the rate of compensatory evolution. It is shown that the effects of indirect compensation are very strong. We find that recombination does not slow down the rate of compensatory evolution as predicted by the classical model. Instead, compensatory substitutions may be relatively frequent, even if linkage between the focal interacting sites is loose, selection against deleterious mutations is strong, and mutation rate is low. We compare our theoretical results with data on RNA secondary structures from vertebrate introns.
UR - http://www.scopus.com/inward/record.url?scp=84947747734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947747734&partnerID=8YFLogxK
U2 - 10.1016/j.jtbi.2015.10.008
DO - 10.1016/j.jtbi.2015.10.008
M3 - Article
C2 - 26506471
AN - SCOPUS:84947747734
VL - 388
SP - 96
EP - 107
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
SN - 0022-5193
ER -