With the exception of a single Y chromosome from Morocco with the M269 mutation (haplotype 117b), all group IX African chromosomes are characterized by the presence of the M173 and M207 derived alleles and the absence of the downstream mutations (haplotype 117). Haplotype 117 was found only in Cameroon, where it accounts for 26% of the chromosomes (40% in northern Cameroon). Chromosomes from Cameroon with this haplotype are the same as those reported in a previous article as belonging to haplotype 1C (Scozzari et al. ¹⁹⁹⁹). Since, so far, no population data have been published for the M269 mutation, in the present study 102 European and 8 Middle Eastern Y chromosomes were analyzed for this marker. These chromosomes had been previously classified as haplotype 1 by Scozzari et al. (2001) (DYS257 A/ SRY₁₀₈₃₁ G chromosomes, corresponding to haplotypes 110–118 and 123 [group IX], and 124–131 [group X] of Underhill et al. [2001b]). In contrast to the group IX chromosomes from Cameroon, all western Eurasian chromosomes were found to carry the M269 derived allele.

Khoisan Origins and Genetic Affinities

The Khoisan people exhibit a number of characteristics, such as light skin color, female steatopygia and macronymphia, and the presence of “click” sounds in their language, that make them markedly distinct from neighboring Bantu groups and other sub-Saharan Africans (Hiernaux 1974; Cavalli-Sforza et al. ¹⁹⁹⁴). Genetic analyses based on autosomal (Excoffier et al. ¹⁹⁸⁷; Cavalli-Sforza et al. ¹⁹⁹⁴) and mtDNA (Watson et al. ¹⁹⁹⁶; Chen et al. ²⁰⁰⁰) markers also showed that the Khoisan represent an outlier group in the context of sub-Saharan Africa, a finding confirmed by our correspondence analysis (fig. 3B). If we exclude the recent introduction of Bantu chromosomes (see above), the current Khoisan Y chromosomes fall into only four distinct subsets: those carrying the M51 (haplotype 4) and M14 (haplotypes 6 and 7) mutations, which are Khoisan-specific, and those characterized by the M112 (haplotype 15) and M35 (haplotype 35) mutations, which are shared with Pygmies and Ethiopians, respectively. These haplotypes are not closely related and coalesce to the root of the Y-chromosome phylogeny, suggesting that, as previously noted (Scozzari et al. ¹⁹⁹⁹), the gene pool of modern Khoisan people is the result of several admixture events, ending with Bantu population-mediated gene flow. Of note is the observation that the M51 lineage found in the Khoisan, which represents 26% of the Khoisan chromosomes analyzed to date, and the M13 lineage, which is found at a high frequency in Ethiopia (41%, including data from Underhill et al. [2000]), are united by M220, which is indicative of a shared common paternal ancestry. These findings, along with the sharing of haplotype 35 (table 2 and fig. 2), suggest a certain degree of ancient genetic affinity between Khoisan and Ethiopians. Hypotheses about the presence of some ancestors of modern Khoisan in eastern Africa have been made on the basis of Khoisan-like skeletal materials found in eastern and northeastern Africa (Bräuer 1978; Tobias 1978) and on the basis of linguistic affinities with some modern eastern African populations that also use “clicks” in their languages (Greenberg 1963). Such a scenario is reinforced by the observation that haplotype 28, from which haplotype 35 is derived, and haplotype 5, which is phylogenetically the closest to haplotypes 2 and 4, have been found in Ethiopia but not in southern Africa. Although these data support the sharing of an ancestral gene pool between Khoisan and Ethiopians, the high divergence of haplotypes carrying the M13 and M51 mutations (fig. 1, and the large number of mutations observed in a more complete tree than that in fig. 1 [L.L.C.-S., unpublished data]) and the extensive interpopulation STR diversity observed within haplotype 35 (fig. 4E) indicate that the Ethiopian and Khoisan Y-chromosome components have been separated for a considerable period of time.

Group IX Chromosomes in Sub-Saharan Africa: An Asian Origin?

In sub-Saharan Africa, the majority of the haplotypes fall within one of three groups (groups I–III in fig. 1) sharing the ancestral allelic state at the M89 locus. In contrast, the majority of non-African chromosomes carry the derived allele at this locus (groups VI–X in fig. 1). The only notable exception in sub-Saharan Africa is represented by a set of chromosomes that harbors the M207 and M173 mutations (haplotype 117 in fig. 1) and is found in different linguistic groups of northern Cameroon, at an average frequency of 40%. These two mutations define all members of group IX (haplotypes 110–123 in the study by Underhill et al. [2001b]), a haplogroup that shares the M9 mutation with haplogroups VII, VIII, and X (haplotypes 81–96, 97–109, and 124–131, respectively, in the study by Underhill et al. [2001b]). So far, all group IX chromosomes from Europe and the Middle East that we analyzed were found to carry either the M269 mutation (haplotype 117b and derivatives) or the SRY₁₀₈₃₁ and M17 mutations (haplotypes 119–122). Both of these groups of haplotypes are very common in western Eurasia but harbor opposite frequency clines (R.S., unpublished data; P.A.U., unpublished data). Haplotypes carrying the SRY₁₀₈₃₁ mutation are not restricted to western Eurasia but are also common in central, northern, and southern Asia (Hammer et al. ²⁰⁰¹; Karafet et al. ²⁰⁰¹). Exclusive to Asia is a third group IX lineage, characterized by the M73 mutation (haplotype 123). The fourth and last group IX lineage identified so far is represented by the Cameroonian haplotype 117, which lacks any known downstream mutations.

How can the presence of Group IX chromosomes at considerable frequency in Cameroon be explained? A priori, we can envision three possibilities. First, group IX chromosomes in Cameroon are due to rather recent male gene flow from Europe or the Near East. Second, the entire M9 superclade (haplogroups VII–X) has an African origin. Third, group IX chromosomes in Cameroon represent a footprint of a male back migration from Asia to Africa. The first scenario seems to be very unlikely, because only derived haplotypes, carrying the M269 or M17/SRY₁₀₈₃₁ mutations, have been detected in western Eurasia. The second hypothesis, an African origin of the M9 superclade that includes haplotype 117, would imply a subsequent impressive extinction of derivative lineages in sub-Saharan Africa, since no other haplotypes carrying the M9 mutation (haplogroups VII–X) have been observed in this region (the only exception being represented by a few haplotype 109 chromosomes found in the Fulbe from Cameroon). The last scenario, that of a back migration from Asia to Africa, currently appears to be by far the most plausible. This is because most of the M9 haplotypes (the majority of group VII and VIII lineages, as well as some group IX and X lineages reported by Underhill et al. [2000]) have been observed only in Asia. Moreover, this possibility appears to be further supported by the recent finding of the UTY2+/M173− intermediate haplotype (Karafet et al. ²⁰⁰¹) in central and northeastern Asia (the UTY2 marker in the study by Karafet et al. [2001] corresponds to M207 in the present study).

On the basis of phylogeographic Y-haplotype analyses, Asia has been regarded as the source of several old migrations leading to the peopling of America, Oceania, and Europe (Karafet et al. ¹⁹⁹⁹; Santos et al. ¹⁹⁹⁹; Hammer et al. ²⁰⁰¹; Underhill et al. ^2001b; Wells et al. ²⁰⁰¹; Lell et al. ²⁰⁰²). In particular, M173-bearing chromosomes in Europe are considered to delineate an ancient expansion from Asia during the Upper Paleolithic, ~30,000 years ago (Semino et al. ²⁰⁰⁰; Underhill et al. ^2001b; Wells et al. ²⁰⁰¹). It is quite reasonable to hypothesize that an ancient Asian gene pool was the source of both the European (haplotype 117b) and Cameroonian (haplotype 117) M173 chromosomes. The fact that haplotype 117 is rare or absent in Asia (P.A.U., unpublished data) or the Middle East (present study), suggests that a large portion of its microsatellite diversity in Cameroon accumulated within the African continent after the proposed back-migration event, probably as a consequence of a population expansion. The coalescence age of the African haplotype 117, which we estimated as 4,100 years (95% CI 2,400–8,060 years), could thus represent a date for such an expansion and a lower limit for the time of entry into Africa. The occurrence of the latter event may not necessarily be recent. Although anthropological evidence indicates recent movements between western Asia and Africa by pastoralists (Cavalli-Sforza et al. ¹⁹⁹⁴), the phylogeography and diversity patterns of M173-associated lineages suggest an earlier demographic history. The absence in northern Cameroon of Y haplotypes affiliated with the recolonization of Europe following the Last Glacial Maximum, as well as the subsequent Neolithic transition (Semino et al. ²⁰⁰⁰), is consistent with this interpretation. Interestingly, phylogenetic analysis of primate T-cell lymphotropic viruses type 1 indicate a putative Asian origin (Vandamme et al. ¹⁹⁹⁸) followed by a simian- or human-mediated introduction to Africa 20,000 years ago (Van Dooren et al. ²⁰⁰¹).

An ancient human back migration from Asia to Africa had already been proposed by Altheide and Hammer (1997) and Hammer et al. (1998, 2001), on the basis of nested cladistic analysis of Y-chromosome data. They suggested that the presence of YAP⁺ chromosomes in Africa was due to such an event, but this has recently been questioned by Underhill et al. (2001b) and Underhill and Roseman (2001), primarily on the basis of the Asian-specific YAP⁺ subclade that neutralizes the previous phylogenetic inferences. Thus, the only evidence of a migration from Asia to sub-Saharan Africa that is fully supported by Y-chromosome data relies, at least for the moment, on the finding of haplogroup IX chromosomes in Cameroon.

Interestingly, a frequency of 13% has been previously reported in an Egyptian sample for a group of chromosomes defined as haplotype 1C (Scozzari et al. ¹⁹⁹⁹) and closely related to the M173 chromosomes. Unfortunately, this sample was not available for the present study. Although we cannot define more precisely the haplotype of the Egyptian 1C Y chromosomes, it is worth noting that four of six of these chromosomes showed dinucleotide microsatellite haplotypes that matched or were one-step neighbors of the M173 chromosomes found in Cameroon.

The genetic uniqueness of the northern Cameroon populations outlined here is based entirely on Y-chromosome evidence. It is desirable that additional markers are examined to provide a complement to the Y-chromosome data. In particular, an mtDNA analysis might help to evaluate possible sex-specific differences in migratory behavior.

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The genetic structure of 126 Ethiopian and 139 Senegalese Y chromosomes was investigated by a hierarchical analysis of 30 diagnostic biallelic markers selected from the worldwide Y-chromosome genealogy. The present study reveals that (1) only the Ethiopians share with the Khoisan the deepest human Y-chromosome clades (the African-specific Groups I and II) but with a repertoire of very different haplotypes; (2) most of the Ethiopians and virtually all the Senegalese belong to Group III, whose precursor is believed to be involved in the first migration out of Africa; and (3) the Ethiopian Y chromosomes that fall into Groups VI, VIII, and IX may be explained by back migrations from Asia. The first observation confirms the ancestral affinity between the Ethiopians and the Khoisan, which has previously been suggested by both archaeological and genetic findings.