Y chromosome sequence variation and the history of human populations.

Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.

The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data.

We report a comparison of worldwide genetic variation among 255 individuals by using autosomal, mitochondrial, and Y-chromosome polymorphisms. Variation is assessed by use of 30 autosomal restriction-site polymorphisms (RSPs), 60 autosomal short-tandem-repeat polymorphisms (STRPs), 13 Alu-insertion polymorphisms and one LINE-1 element, 611 bp of mitochondrial control-region sequence, and 10 Y-chromosome polymorphisms. Analysis of these data reveals substantial congruity among this diverse array of genetic systems. With the exception of the autosomal RSPs, in which an ascertainment bias exists, all systems show greater gene diversity in Africans than in either Europeans or Asians. Africans also have the largest total number of alleles, as well as the largest number of unique alleles, for most systems. GST values are 11%-18% for the autosomal systems and are two to three times higher for the mtDNA sequence and Y-chromosome RSPs. This difference is expected because of the lower effective population size of mtDNA and Y chromosomes. A lower value is seen for Y-chromosome STRs, reflecting a relative lack of continental population structure, as a result of rapid mutation and genetic drift. Africa has higher GST values than does either Europe or Asia for all systems except the Y-chromosome STRs and Alus. All systems except the Y-chromosome STRs show less variation between populations within continents than between continents. These results are reassuring in their consistency and offer broad support for an African origin of modern human populations.

Y chromosome haplotypes reveal prehistorical migrations to the Himalayas.

By using 19 Y chromosome biallelic markers and 3 Y chromosome microsatellite markers, we analyzed the genetic structure of 31 indigenous Sino-Tibetan speaking populations (607 individuals) currently residing in East, Southeast, and South Asia. Our results showed that a T to C mutation at locus M122 is highly prevalent in almost all of the Sino-Tibetan populations, implying a strong genetic affinity among populations in the same language family. Furthermore, the extremely high frequency of H8, a haplotype derived from M122C, in the Sino-Tibetan speaking populations in the Himalayas including Tibet and northeast India indicated a strong bottleneck effect that occurred during a westward and then southward migration of the founding population of Tibeto-Burmans. We, therefore, postulate that the ancient people, who lived in the upper-middle Yellow River basin about 10,000 years ago and developed one of the earliest Neolithic cultures in East Asia, were the ancestors of modern Sino-Tibetan populations.

Population growth of human Y chromosomes: a study of Y chromosome microsatellites.

We use variation at a set of eight human Y chromosome microsatellite loci to investigate the demographic history of the Y chromosome. Instead of assuming a population of constant size, as in most of the previous work on the Y chromosome, we consider a model which permits a period of recent population growth. We show that for most of the populations in our sample this model fits the data far better than a model with no growth. We estimate the demographic parameters of this model for each population and also the time to the most recent common ancestor. Since there is some uncertainty about the details of the microsatellite mutation process, we consider several plausible mutation schemes and estimate the variance in mutation size simultaneously with the demographic parameters of interest. Our finding of a recent common ancestor (probably in the last 120,000 years), coupled with a strong signal of demographic expansion in all populations, suggests either a recent human expansion from a small ancestral population, or natural selection acting on the Y chromosome.

Genetic evidence for a higher female migration rate in humans.

Mitochondrial DNA and the Y chromosome have been used extensively in the study of modern human origins and other phylogenetic questions, but not in the context of their sex-specific modes of transmission. mtDNA is transmitted exclusively by females, whereas the Y chromosome is passed only among males. As a result, differences in the reproductive output or migration rate of males and females will influence the geographic patterns and relative level of genetic diversity on the Y chromosome, autosomes and mtDNA (ref. 1). We have found that Y chromosome variants tend to be more localized geographically than those of mtDNA and the autosomes. The fraction of variation within human populations for Y chromosome single nucleotide polymorphisms (SNPs) is 35.5%, versus 80-85% for the autosomes and mtDNA (refs 6-8). A higher female than male migration rate (via patrilocality, the tendency for a wife to move into her husband's natal household) explains most of this discrepancy, because diverse Y chromosomes would enter a population at a lower rate than mtDNA or the autosomes. Polygyny may also contribute, but the reduction of variation within populations that we measure for the Y chromosome, relative to the autosomes and mitochondrial DNA, is of such magnitude that differences in the effective population sizes of the sexes alone are insufficient to produce the observation.

Cw*1701 defines a divergent african HLA-C allelic lineage.

The complete sequence of a new HLA-C allele, Cw*1701, was determined from a South African Zulu individual. Unique features that distinguish Cw*1701 from other HLA-C alleles include multiple point substitutions and an 18 nucleotide insertion in exon 5, which encodes the transmembrane domain. In a phylogenetic analysis of HLA-C sequences, Cw*1701 forms a third, distinct allelic lineage. A comparison of the transmembrane domain of Cw*1701 with other HLA-B and -C alleles reveals that duplications and deletions have been common in the evolution of these loci. A polymerase chain reaction based typing method was used to determine the distribution of this unusual allele in human populations. In contrast to the other two lineages of HLA-C alleles, the Cw*17 lineage is found at high frequencies only in populations of African descent. In addition, the HLA-B/Cw*17 haplotype diversity is higher in Africa.

Geographic clustering of human Y-chromosome haplotypes.

Five polymorphic markers on the Y-chromosome (mostly microsatellites) were typed in 121 individuals from 13 populations around the world. With these markers 78 different haplotypes were detected. Haplotypes present more than once tend to be shared by individuals from the same population or continent. A reconstruction of haplotype phylogeny also indicates significant geographic structure in the data. Based on the similarity of the haplotypes, population relationships were examined and found to be largely concordant with those obtained with other markers. Even though the sample size and the number of markers are small, there is very signficant clustering of the haplotypes by continent of origin.

Construction of human Y-chromosomal haplotypes using a new polymorphic A to G transition.

We report the discovery of a polymorphic A to G transition found on the human Y chromosome by sequencing Y-specific sequence-tagged sites (STSs). It shows maximal linkage disequilibrium with a previously described Alu insertional polymorphism. We analyze further an apparently African Y chromosome which seems to have entered a Mexican Mayan population several generations ago. Using the newly discovered transition and the Y-specific polymorphic Alu insertion, we discuss how the chromosome's haplotype information might be used to answer questions of human origins and migrations.