Microsatellite diversity and the demographic history of modern humans.
Journal: 1997/May - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
PUBMED: 9096352
Abstract:
We have examined differences in diversity at 60 microsatellite loci among human population samples from three major continental groups to evaluate the hypothesis of greater African diversity in this rapidly evolving class of loci. Application of a statistical test that assumes equal mutation rates at all loci fails to demonstrate differences in microsatellite diversity, while a randomization test that does not make this assumption finds that Africans have significantly greater microsatellite diversity (P < 10(-8)) than do Asians and Europeans. Greater African diversity is most apparent at loci with smaller overall variance in allele size, suggesting that the record of population history has been erased at repeat loci with higher mutation rates. A power analysis shows that only 35-40 microsatellites are needed to establish this difference statistically, demonstrating the considerable evolutionary information contained in these systems. On average, African populations have approximately 20% greater microsatellite diversity than do Asian and European populations. A comparison of continental diversity differences in microsatellites and mtDNA sequences suggests earlier demographic expansion of the ancestors of Africans.
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Proc Natl Acad Sci U S A 94(7): 3100-3103

Microsatellite diversity and the demographic history of modern humans

Eccles Institute of Human Genetics, University of Utah Health Sciences Center, and Department of Anthropology, University of Utah, Salt Lake City, UT 84112; Department of Medical Genetics, University of Helsinki, FIN-00014, Helsinki, Finland; Department of Anthropology, Pennsylvania State University, 409 Carpenter Building, University Park, PA 16802
To whom reprint requests should be addressed. e-mail: ude.hatu.sciteneg.nido@jbl.

Henry C. Harpending

Accepted 1997 Jan 23.

Abstract

We have examined differences in diversity at 60 microsatellite loci among human population samples from three major continental groups to evaluate the hypothesis of greater African diversity in this rapidly evolving class of loci. Application of a statistical test that assumes equal mutation rates at all loci fails to demonstrate differences in microsatellite diversity, while a randomization test that does not make this assumption finds that Africans have significantly greater microsatellite diversity (P < 10) than do Asians and Europeans. Greater African diversity is most apparent at loci with smaller overall variance in allele size, suggesting that the record of population history has been erased at repeat loci with higher mutation rates. A power analysis shows that only 35–40 microsatellites are needed to establish this difference statistically, demonstrating the considerable evolutionary information contained in these systems. On average, African populations have ≈20% greater microsatellite diversity than do Asian and European populations. A comparison of continental diversity differences in microsatellites and mtDNA sequences suggests earlier demographic expansion of the ancestors of Africans.

Abstract

Greater genetic diversity in human populations from Africa has been a cornerstone of the argument for an African origin of modern humans, since this greater diversity suggests a greater “age” for African populations. In demographic terms, the greater age hypothesis has been interpreted in at least two ways: first, that human populations outside Africa are descendants of emigrants from a large African population (1); and, second, that all modern humans are derived from expansions from a restricted founding population and that the expansion of African ancestors occurred much earlier than those of populations outside Africa (2, 3).

Many recent empirical studies have demonstrated greater genetic diversity in African populations than in non-African populations. Some of the strongest evidence in support of increased African diversity comes from studies of mtDNA (4), the CD4 microsatellite and a nearby Alu polymorphism (1), and D16S309, a minisatellite system (5). However, each of these systems represents essentially a single locus subject to large stochastic variation. Relethford and Harpending (6) report that a multivariate generalization of variance is greater in craniometric traits from African populations than in populations from Europe and Asia, but the effects of environmental sources of variance were not known. Bowcock et al. (7) showed that heterozygosity in Africans was significantly greater in a sample of 30 dinucleotide microsatellite loci. However, the loci they analyzed were all on chromosomes 13 and 15, violating independence assumptions of their statistical test. Jorde et al. (8) also demonstrated greater African heterozygosity in a sample of 30 tetranucleotide microsatellite loci, but this difference was not statistically significant.

In contrast, classical markers and nuclear restriction fragment length polymorphisms do not show elevated African diversity (9, 10). For these loci, Europeans and occasionally Asians are the most diverse population group, perhaps reflecting ascertainment bias in discovering these systems because they were polymorphic in Europeans (11). This ascertainment bias can be large enough to account for excess heterozygosity in systems in which the average heterozygosity is <0.35 (12). Most classical markers and restriction fragment length polymorphisms fall into this category, making ascertainment bias a possible explanation for the lack of excess African diversity in these systems.

The published genetic data, while mostly supportive of this pattern of elevated African genetic diversity at loci with high mutation rates, are by no means definitive. There is little statistical support for the pattern. To test further the hypothesis of increased African diversity, we have examined 60 unlinked microsatellite loci in a worldwide sample of humans. Using methods appropriate for such systems, we demonstrate a statistically significant elevation of African genetic diversity.

Acknowledgments

We thank Drs. John Relethford, Andrew Clark, and Sarah Tishkoff for comments and suggestions on the manuscript. Some of the Asian samples were contributed by Drs. Ken and Judy Kidd, and some of the African samples were contributed by Dr. Trefor Jenkins. This research was supported by National Science Foundation Grants DBS-9310105, SBR-9514733, and SBR-9512178; National Institutes of Health (NIH) Grant RR-00064; the Technology Access Center of the Utah Human Genome Project (NIH HG00199); and a supplemental equipment grant from the University of Utah. M.B. was supported by a Clinical Associate Physician fellowship (NIH M01-00064).

Acknowledgments

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