Abstract
Population geneticists work with a nonrandom sample of the human genome. Conventional practice ensures that unusually variable loci are most likely to be discovered and thus included in the sample of loci. Consequently, estimates of average heterozygosity are biased upward. In what follows we describe a model of this bias. When the mutation rate varies among loci, bias is increased. This effect is only moderate, however, so that a model of invariant mutation rates provides a reasonable approximation. Bias is pronounced when estimated heterozygosity is < approximately 35% Consequently, it probably affects estimates from classical polymorphisms as well as from restriction-site polymorphisms. Estimates from short-tandem-repeat polymorphisms have negligible bias, because of their high heterozygosity. Bias should vary not only among categories of polymorphism but also among populations. It should be largest in European populations, since these are the populations in which most polymorphisms were discovered. As this argument predicts, European estimates exceed those of Africa and Asia at systems with large bias. The magnitude of this European excess is consistent with the version of our model in which mutation rates vary across loci.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bowcock A. M., Ruiz-Linares A., Tomfohrde J., Minch E., Kidd J. R., Cavalli-Sforza L. L. High resolution of human evolutionary trees with polymorphic microsatellites. Nature. 1994 Mar 31;368(6470):455–457. doi: 10.1038/368455a0. [DOI] [PubMed] [Google Scholar]
- Chakraborty R., Fuerst P. A., Nei M. Statistical Studies on Protein Polymorphism in Natural Populations. III. Distribution of Allele Frequencies and the Number of Alleles per Locus. Genetics. 1980 Apr;94(4):1039–1063. doi: 10.1093/genetics/94.4.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harris H., Hopkinson D. A. Average heterozygosity per locus in man: an estimate based on the incidence of enzyme polymorphisms. Ann Hum Genet. 1972 Jul;36(1):9–20. doi: 10.1111/j.1469-1809.1972.tb00578.x. [DOI] [PubMed] [Google Scholar]
- Jorde L. B., Bamshad M. J., Watkins W. S., Zenger R., Fraley A. E., Krakowiak P. A., Carpenter K. D., Soodyall H., Jenkins T., Rogers A. R. Origins and affinities of modern humans: a comparison of mitochondrial and nuclear genetic data. Am J Hum Genet. 1995 Sep;57(3):523–538. doi: 10.1002/ajmg.1320570340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mountain J. L., Cavalli-Sforza L. L. Inference of human evolution through cladistic analysis of nuclear DNA restriction polymorphisms. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6515–6519. doi: 10.1073/pnas.91.14.6515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nei M., Chakraborty R., Fuerst P. A. Infinite allele model with varying mutation rate. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4164–4168. doi: 10.1073/pnas.73.11.4164. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nei M., Roychoudhury A. K. Genic variation within and between the three major races of man, Caucasoids, Negroids, and Mongoloids. Am J Hum Genet. 1974 Jul;26(4):421–443. [PMC free article] [PubMed] [Google Scholar]
- Sherry S. T., Rogers A. R., Harpending H., Soodyall H., Jenkins T., Stoneking M. Mismatch distributions of mtDNA reveal recent human population expansions. Hum Biol. 1994 Oct;66(5):761–775. [PubMed] [Google Scholar]
- Watkins W. S., Bamshad M., Jorde L. B. Population genetics of trinucleotide repeat polymorphisms. Hum Mol Genet. 1995 Sep;4(9):1485–1491. doi: 10.1093/hmg/4.9.1485. [DOI] [PubMed] [Google Scholar]