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Open Access Highly Accessed Research article

A genetic polymorphism evolving in parallel in two cell compartments and in two clades

Ward B Watt12*, Richard R Hudson3, Baiqing Wang1 and Eddie Wang14

Author affiliations

1 Department of Biology, Stanford University, Stanford, CA 94305-5020, USA

2 Rocky Mountain Biological Laboratory, Crested Butte, CO 81224, USA

3 Department of Ecology and Evolution, University of Chicago, Chicago, IL, 60637, USA

4 Present address: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 0213, USA

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Citation and License

BMC Evolutionary Biology 2013, 13:9  doi:10.1186/1471-2148-13-9

Published: 12 January 2013

Abstract

Background

The enzyme phosphoenolpyruvate carboxykinase, PEPCK, occurs in its guanosine-nucleotide-using form in animals and a few prokaryotes. We study its natural genetic variation in Colias (Lepidoptera, Pieridae). PEPCK offers a route, alternative to pyruvate kinase, for carbon skeletons to move between cytosolic glycolysis and mitochondrial Krebs cycle reactions.

Results

PEPCK is expressed in both cytosol and mitochondrion, but differently in diverse animal clades. In vertebrates and independently in Drosophila, compartment-specific paralogous genes occur. In a contrasting expression strategy, compartment-specific PEPCKs of Colias and of the silkmoth, Bombyx, differ only in their first, 5, exons; these are alternatively spliced onto a common series of following exons. In two Colias species from distinct clades, PEPCK sequence is highly variable at nonsynonymous and synonymous sites, mainly in its common exons. Three major amino acid polymorphisms, Gly 335 ↔ Ser, Asp 503 ↔ Glu, and Ile 629 ↔ Val occur in both species, and in the first two cases are similar in frequency between species. Homology-based structural modelling shows that the variants can alter hydrogen bonding, salt bridging, or van der Waals interactions of amino acid side chains, locally or at one another’s sites which are distant in PEPCK’s structure, and thus may affect its enzyme function. We ask, using coalescent simulations, if these polymorphisms’ cross-species similarities are compatible with neutral evolution by genetic drift, but find the probability of this null hypothesis is 0.001 ≤ P ≤ 0.006 under differing scenarios.

Conclusion

Our results make the null hypothesis of neutrality of these PEPCK polymorphisms quite unlikely, but support an alternative hypothesis that they are maintained by natural selection in parallel in the two species. This alternative can now be justifiably tested further via studies of PEPCK genotypes’ effects on function, organismal performance, and fitness. This case emphasizes the importance, for evolutionary insight, of studying gene-specific mechanisms affected by natural genetic variation as an essential complement to surveys of such variation.

Keywords:
Amino acid polymorphism; Coalescent simulation; Glycolysis; Intramolecular bond variation; Neutral null hypothesis; Parallel evolution; Phosphoenolpyruvate carboxykinase; Selection hypothesis; Splice variation