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MBE Advance Access published online on June 16, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh193
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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Accepted June 1, 2004

Original Articles

Average Allozyme Heterozygosity in Vertebrates Correlates with Ka/Ks Measured in the Human-Mouse Lineage

David O. F. Skibinski 1* Robert D. Ward 2

1 School of Biological Sciences, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK
2 CSIRO Marine Research, GPO Box 1538, Hobart, Tasmania 7001, Australia

* To whom correspondence should be addressed. E-mail: d.o.f.skibinski{at}swansea.ac.uk.


  Abstract

It is well established that different allozyme proteins vary in heterozygosity in averages made over large numbers of species. For example, the enzyme 6-phosphogluconate dehydrogenase has a much higher average heterozygosity than glutamate dehydrogenase. Allozyme data alone provide insufficient power to determine the evolutionary cause of such a difference. Many studies have now been carried out on the DNA sequences coding for allozymes. These have identified diverse selective and non-selective causes of polymorphisms at individual loci. However the studies are mainly in a small number of model species; thus it is difficult to identify from these DNA studies specific causes of global average heterozygosity differences among allozyme proteins. Here we demonstrate that estimates of average heterozygosity for 37 allozyme proteins in vertebrates correlate positively with Ka and Ka/Ks but not with Ks, measured in the human-mouse lineage. The values of Ka/Ks are less than 0.25, and Ka/Ks is negatively correlated with subunit number (quaternary structure), a measure of structural constraint. Proteins with lower levels of constraint have higher values of both Ka/Ks and heterozygosity. These results better support the hypothesis that differences in average allozyme diversity between proteins are more closely related to differences in the level of purifying selection than to differences in the underlying mutation rate or level of positive selection.

Keywords: allozyme, heterozygosity, Ka, Ks, constraint, substitution
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