MBE Advance Access published online on February 12, 2009
Molecular Biology and Evolution, doi:10.1093/molbev/msp024
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Research Article |
Haplotypic background of a private allele at high frequency in the Americas
1 Department of Anthropology, University of California, Davis, Davis, California, United States of America
2 Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of America
3 Department of Evolutionary Biology, EBC, Uppsala University, Uppsala, Sweden
4 Department of Anthropology, University of Kansas, Lawrence, Kansas, United States of America
5 Department of Anthropology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
6 Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland, United States of America
7 Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America
8 Department of Anthropology, University of Illinois, Urbana-Champaign, Urbana, Illinois, United States of America
9 Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia
10 Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia
11 Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, United States of America
12 California National Primate Research Center, Davis, California, United States of America
To whom correspondence should be addressed: Kari Britt Schroeder, Department of Anthropology, 330 Young Hall, University of California, Davis, One Shields Ave. Davis, CA 95616, email: kbschroeder{at}ucdavis.edu, phone: 530-752-8570, fax: 530-752-8885
Received for publication September 11, 2008. Revision received December 20, 2008. Accepted for publication January 16, 2009.
Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 SNPs across 
500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the "American Modal Haplotype" (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared to other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared to that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all modern Native Americans and Western Beringians trace a large portion of their ancestry to a single founding population which may have been isolated from other Asian populations prior to expanding into the Americas.
Key Words: Private allele • D9S1120 • Homo sapiens • Native American • migration