Mitochondrial DNA and Y-chromosomal stratification in Iran: relationship between Iran and the Arabian Peninsula.

Modern day Iran is strategically located in the tri-continental corridor uniting Africa, Europe and Asia. Several ethnic groups belonging to distinct religions, speaking different languages and claiming divergent ancestries inhabit the region, generating a potentially diverse genetic reservoir. In addition, past pre-historical and historical events such as the out-of-Africa migrations, the Neolithic expansion from the Fertile Crescent, the Indo-Aryan treks from the Central Asian steppes, the westward Mongol expansions and the Muslim invasions may have chiseled their genetic fingerprints within the genealogical substrata of the Persians. On the other hand, the Iranian perimeter is bounded by the Zagros and Albrez mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts, which may have restricted gene flow from neighboring regions. By utilizing high-resolution mitochondrial DNA (mtDNA) markers and reanalyzing our previously published Y-chromosomal data, we have found a previously unexplored, genetic connection between Iranian populations and the Arabian Peninsula, likely the result of both ancient and recent gene flow. Furthermore, the regional distribution of mtDNA haplogroups J, I, U2 and U7 also provides evidence of barriers to gene flow posed by the two major Iranian deserts and the Zagros mountain range.

Insights on human evolution: an analysis of Alu insertion polymorphisms.

We analyzed the genetic profile of 563 individuals from 12 geographically targeted human populations from Europe, Asia and Africa using 27 human-specific polymorphic Alu insertions. Phylogenetic analyses indicated a clear correspondence between genetic profiles and historical patterns of gene flow and genetic drift. Sub-Saharan African populations (Benin, Cameroon, Kenya and Rwanda) formed a visibly differentiated cluster, indicating the role of the Sahara desert as a strong natural barrier to gene flow. Moreover, a higher than expected genetic affinity between populations from Europe, North Africa and Asia was detected, probably reflecting the homogenizing effects of bidirectional migratory processes between Eurasia and North Africa during the Plio-Pleistocene and Neolithic periods or the insensitivity of these markers in discriminating between these groups. The Ami aborigines of Formosa present a distinctive degree of genetic uniqueness from all the other groups, consistent with a pattern of isolation by distance, small population size and, accordingly, substantial genetic drift. We further tested all 27 Alu loci for their potential usefulness as ancestry informative markers (AIMs). On the basis of differences between weighted allelic frequencies (delta-values) and F(ST) values, we propose that 11 of the 27 Alu elements could be useful as part of the current AIM panels to assess phylogenetic relationships.

North Indian Muslims: enclaves of foreign DNA or Hindu converts?

The mtDNA composition of two Muslim sects from the northern Indian province of Uttar Pradesh, the Sunni and Shia, have been delineated using sequence information from hypervariable regions 1 and 2 (HVI and HVII, respectively) as well as coding region polymorphisms. A comparison of this data to that from Middle Eastern, Central Asian, North East African, and other Indian groups reveals that, at the mtDNA haplogroup level, both of these Indo-Sunni and Indo-Shia populations are more similar to each other and other Indian groups than to those from the other regions. In addition, these two Muslim sects exhibit a conspicuous absence of West Asian mtDNA haplogroups suggesting that their maternal lineages are of Indian origin. Furthermore, it is noteworthy that the maternal lineage data indicates differences between the Sunni and Shia collections of Uttar Pradesh with respect to the relative distributions of Indian-specific M sub-haplogroups (Indo Shia > Indo Sunni) and the R haplogroup (Indo Sunni > Indo Shia), a disparity that does not appear to be related to social status or geographic regions within India. Finally, the mtDNA data integrated with the Y-chromosome results from an earlier study, which indicated a major Indian genetic (Y-chromosomal) contribution as well, suggests a scenario of Hindu to Islamic conversion in these two populations. However, given the substantial level of the African/Middle Eastern YAP lineage in the Indo-Shia versus its absence in the Indo-Sunni, it is likely that this conversion was somewhat gender biased in favor of females in the Indo-Shia.

Polymorphic Alu insertions and genetic diversity among African populations.

Thorough assessment of modern genetic diversity and interpopulation affinities within the African continent is essential for understanding the processes that have been at work during the course of worldwide human evolution. Regardless of whether autosomal, Y-chromosome, or mtDNA markers are used, allele- or haplotype-frequency data from African populations are necessary in setting the framework for the construction of global population phylogenies. In the present study we analyze genetic differentiation and population structure in a data set of nine African populations using 12 polymorphic Alu insertions (PAls). Furthermore, to place our findings within a global context, we also examined an equal number of non-African groups. Frequency data from 456 individuals presented for the first time in this work plus additional data obtained from the literature indicate an overall pattern of higher intrapopulation diversity in sub-Saharan populations than in northern Africa, a prominent differentiation between these two locations, an appreciably high degree of transcontinental admixture in Egypt, and significant discontinuity between Morocco and the Iberian peninsula. Moreover, the topologies of our phylogenetic analyses suggest that out of the studied sub-Saharan groups, the southern Bantu population of Sotho/ Tswana presents the highest level of antiquity, perhaps as a result of ancestral or acquired Khoisan genetic signals. Close affinities of eastern sub-Saharan populations with Egypt in the phylogenetic trees may indicate the existence of gene flow along the Nile River.

Superimposing polymorphism: the case of a point mutation within a polymorphic Alu insertion.

The COL3A1 Alu insertion is a member of the AluY subfamily. It has been found to be absent in non-human primates and polymorphic in worldwide human populations. The integration of the element into the human genome seems to have preceded the initial migration(s) of anatomically modern humans out of the African continent. Although the insertion has been detected in populations from all the continents, its highest frequency values are located within sub-Saharan Africa. The sequence alignment of the COL3A1 insertion from several African individuals revealed a bi-allelic single nucleotide polymorphism (SNP) at the downstream terminus of the element's poly-A tract. Once discovered, a selective PCR procedure was designed to determine the frequency of both alleles in 19 worldwide populations. The A-allele in this binary SNP experiences a clinal increase in the eastward direction from Africa to Southeast Asia and Mongolia, reaching fixation in the two latter regions. The T variant, on the other hand, exhibits a westward clinal increase outside of Africa, with its lowest frequency in Asia and achieving fixation in northern Europe. The presence of this internal SNP extends the usefulness provided by the polymorphic Alu insertion (PAI). It is possible that superimposing polymorphisms like this one found in the COL3A1 locus may accentuate signals from genetic drift events allowing for visualization of recent dispersal patterns.

Two problematic human polymorphic Alu insertions.

Analysis of two previously described polymorphic Alu insertions (Sb19.3 and NBC3) in world-wide human populations generated genotypic frequencies grossly in violation of Hardy-Weinberg equilibrium expectations. GenBank searches at the National Center for Biotechnology Information (NCBI) and sequencing analyses revealed that samples homozygous for the Sb19.3 Alu insertion amplify a band indistinguishable in size to the lack of insertion amplicon, corresponding to a paralogous locus on chromosome 4. This locus displays a very similar sequence (84%) to that flanking the Sb19.3 Alu insertion located at chromosome 19. Moreover, we have determined that NBC3, a different Alu insertion, is not located in the pseudoautosomal region of the Y-chromosome, as previously reported, but in position Yq11.2. Also, the band that mimics the lack of insertion amplicon corresponds to a paralogous locus located at chromosome X with a similarity of 92% to the sequence flanking the NBC3 Alu insertion. Finally, the utilization of newly designed primers avoided amplification from the paralogous loci and allowed a reliable assignation of genotypes for both loci. Unlike previously reported, using our new primers the Y-specific locus NBC3 was found not to be polymorphic in the populations analyzed.