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An empirical test of the concomitantly variable codon hypothesis.

Lauren M F Merlo¹, Mark Lunzer, Antony M Dean

¹Department of Ecology, Evolution, and Behavior, University of Minnesota, 100 Ecology Building, 1987 Upper Buford Circle, Saint Paul, MN 55108, USA.

Proceedings of the National Academy of Sciences of the United States of America

|June 21, 2007

Summary

Molecular evolution models assume independent site evolution, but codependencies (covarions) exist in triosephosphate isomerase (TIM). These covarions are rare in related proteins but increase with genetic distance, challenging phylogenetic assumptions.

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Area of Science:

Molecular Evolution
Biochemistry
Genetics

Background:

A core assumption in molecular evolution models is that individual sequence sites evolve independently.
This assumption lacks empirical validation and may not accurately reflect evolutionary processes.

Purpose of the Study:

To investigate the extent of codependent evolution among sites in the triosephosphate isomerase (TIM) enzyme.
To determine if concomitantly variable codons (covarions) are present and under what conditions they arise.

Main Methods:

Analysis of hybrid triosephosphate isomerase (TIM) proteins to detect functional and structural anomalies.
Examination of codependency patterns in relation to genetic distance between protein sequences.

Main Results:

Codependencies among sites (covarions) were identified in TIM proteins, evidenced by reduced function and misfolding in hybrids.
Covarions were found to be relatively rare in closely related proteins.
The potential for covarions increases significantly with greater genetic distance between proteins.

Conclusions:

The independent evolution assumption in molecular evolution models is challenged by the existence of covarions.
The prevalence of covarions increases with divergence, potentially complicating phylogenetic analyses of distantly related organisms.
Understanding covarions is crucial for accurate reconstruction of ancient evolutionary relationships.