uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Covariation Is a Poor Measure of Molecular Coevolution
Univ Manchester, Fac Life Sci, Manchester, Lancs, England..
Univ Manchester, Fac Life Sci, Manchester, Lancs, England..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology. Univ Manchester, Fac Life Sci, Manchester, Lancs, England..
2015 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 32, no 9, 2456-2468 p.Article in journal (Refereed) Published
Abstract [en]

Recent developments in the analysis of amino acid covariation are leading to breakthroughs in protein structure prediction, protein design, and prediction of the interactome. It is assumed that observed patterns of covariation are caused by molecular coevolution, where substitutions at one site affect the evolutionary forces acting at neighboring sites. Our theoretical and empirical results cast doubt on this assumption. We demonstrate that the strongest coevolutionary signal is a decrease in evolutionary rate and that unfeasibly long times are required to produce coordinated substitutions. We find that covarying substitutions are mostly found on different branches of the phylogenetic tree, indicating that they are independent events that may or may not be attributable to coevolution. These observations undermine the hypothesis that molecular coevolution is the primary cause of the covariation signal. In contrast, we find that the pairs of residues with the strongest covariation signal tend to have low evolutionary rates, and that it is this low rate that gives rise to the covariation signal. Slowly evolving residue pairs are disproportionately located in the protein's core, which explains covariation methods' ability to detect pairs of residues that are close in three dimensions. These observations lead us to propose the "coevolution paradox": The strength of coevolution required to cause coordinated changes means the evolutionary rate is so low that such changes are highly unlikely to occur. As modern covariation methods may lead to breakthroughs in structural genomics, it is critical to recognize their biases and limitations.

Place, publisher, year, edition, pages
2015. Vol. 32, no 9, 2456-2468 p.
Keyword [en]
coevolution, covariation, molecular evolution
National Category
Evolutionary Biology
URN: urn:nbn:se:uu:diva-265928DOI: 10.1093/molbev/msv109ISI: 000361981900019PubMedID: 25944916OAI: oai:DiVA.org:uu-265928DiVA: diva2:866977
Available from: 2015-11-04 Created: 2015-11-04 Last updated: 2015-11-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedFulltext

Search in DiVA

By author/editor
Whelan, Simon
By organisation
Evolutionary Biology
In the same journal
Molecular biology and evolution
Evolutionary Biology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 186 hits
ReferencesLink to record
Permanent link

Direct link