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We examined variation on the nonrecombining portion of the human Y chromosome to investigate human evolution during the last 200,000 years. The Y-specific polymorphic sites included the Y Alu insertional polymorphism or 'YAP' element (DYS287), the poly(A) tail associated with the YAP element, three point mutations in close association with the YAP insertion site, an A-G polymorphic transition (DYS271), and a tetranucleotide microsatellite (DYS19). Global variation at the five bi-allelic sites (DYS271, DYS287, and the three point mutations) gave rise to five 'YAP haplotypes' in 60 populations from Africa, Europe, Asia, Australasia, and the New World (n = 1500). Combining the multi-allelic variation at the microsatellite loci (poly(A) tail and DYS19) with the YAP haplotypes resulted in a total of 27 'combination haplotypes'. All five of the YAP haplotypes and 21 of the 27 combination haplotypes were found in African populations, which had greater haplotype diversity than did populations from other geographical locations. Only subsets of the five YAP haplotypes were found outside of Africa. Patterns of observed variation were compatible with a variety of hypotheses, including multiple human migrations and range expansions.

To better understand the role of malaria in influencing patterns of variation at loci that confer resistance to malaria, we sequenced 11-kb at three unlinked loci in 45 individuals from the Dogon, a population who reside in an endemic malarial environment and ~200 non-African individuals from 4 populations. The first locus, [beta]-globin, contains two alleles that are known to confer resistance to malaria, HbC and HbS. The other two loci, Dmd44 and APXL, ate not subject to malarial selection and likely reflect demographic processes. The HbC allele was found at 10.4% in only the Dogon; the HbS allele was absent in all populations. The frequency spectrum at [beta]-globin in the Dogon exhibited an excess of rare polymorphisms (Tajima's D = -1.15, P>0.10) but did not in the global sample (TD = +0.137, P>0.10) or in any other population sample (-0.047 < TD < +0.836). Tajima's D values at Dmd44 and APXL in the Dogon were less negative than at [beta]-globin ([TD.sub.APXL] = -0.46; [TD.sub.Dmd44] = 0.87) as well as in all non-African populations (-0.24 < [TD.sub.APXL] < +0.76; -0.33 < [TD.sub.Dmd44] < +1.73). The skew in the frequency spectrum at [beta]-globin in the Dogon and the absence of this pattern at Dmd44 and APXL do not support a model of population growth in the Dogon since demographic processes are expected to affect all loci similarly. To further explore the effects of malarial selection at [beta]-globin, a closer examination of sequence variation on the HbC and non-HbC chromosomes is in progress.