Mitochondrial DNA geneflow indicates preferred usage of the Levant Corridor over the Horn of Africa passageway.

Both the Levantine Corridor and the Horn of Africa route have figured prominently in early hominid migrations from Africa to Eurasia. To gauge the importance of these two African-Asian thoroughfares in the demic movements of modern man, we surveyed the mtDNA control region variation and coding polymorphisms of 739 individuals representing ten African and Middle Eastern populations. Two of these collections, Egypt and Yemen, are geographically close to the Levant and Horn of Africa, respectively. In this analysis, we uncover genetic evidence for the preferential use of the Levantine Corridor in the Upper Paleolithic to Neolithic dispersals of haplogroups H, J*, N1b, and T1, in contrast to an overwhelming preference in favor of the Horn of Africa for the intercontinental expansion of M1 during the Middle to Upper Paleolithic. Furthermore, we also observed a higher frequency of sub-Saharan mtDNA compared to NRY lineages in the Middle Eastern collections, a pattern also seen in previous studies. In short, the results of this study suggest that several migratory episodes of maternal lineages occurred across the African-Asian corridors since the first African exodus of modern Homo sapiens sapiens.

The Levant versus the Horn of Africa: evidence for bidirectional corridors of human migrations.

Paleoanthropological evidence indicates that both the Levantine corridor and the Horn of Africa served, repeatedly, as migratory corridors between Africa and Eurasia. We have begun investigating the roles of these passageways in bidirectional migrations of anatomically modern humans, by analyzing 45 informative biallelic markers as well as 10 microsatellite loci on the nonrecombining region of the Y chromosome (NRY) in 121 and 147 extant males from Oman and northern Egypt, respectively. The present study uncovers three important points concerning these demic movements: (1) The E3b1-M78 and E3b3-M123 lineages, as well as the R1*-M173 lineages, mark gene flow between Egypt and the Levant during the Upper Paleolithic and Mesolithic. (2) In contrast, the Horn of Africa appears to be of minor importance in the human migratory movements between Africa and Eurasia represented by these chromosomes, an observation based on the frequency distributions of E3b*-M35 (no known downstream mutations) and M173. (3) The areal diffusion patterns of G-M201, J-12f2, the derivative M173 haplogroups, and M2 suggest more recent genetic associations between the Middle East and Africa, involving the Levantine corridor and/or Arab slave routes. Affinities to African groups were also evaluated by determining the NRY haplogroup composition in 434 samples from seven sub-Saharan African populations. Oman and Egypt's NRY frequency distributions appear to be much more similar to those of the Middle East than to any sub-Saharan African population, suggesting a much larger Eurasian genetic component. Finally, the overall phylogeographic profile reveals several clinal patterns and genetic partitions that may indicate source, direction, and relative timing of different waves of dispersals and expansions involving these nine populations.

Multiple forms of U2 snRNA coexist in the silk moth Bombyx mori.

Eight U2 snRNA variants were isolated from several Bombyx mori U2-specific RT-PCR libraries. U2 sequences and secondary structures were generated and examined in terms of potential RNA and protein interactions. Analysis indicated that nucleotide changes occurred in both stem/loop and single-stranded areas. Changes in the double stranded areas were either compensatory, single substitutions (e.g. C <--> U) or prevented the double-stranded formation of one or two base pairs. The polymorphisms were clustered in moderately conserved regions. Some of the changes observed generated stronger base pairing. Inter-species conserved protein or RNA-binding sites were relatively unaffected. No polymorphic sites were found in known functional sequences. Bombyx mori and Drosophila melanogaster U2 sequences are 95% and 70% similar at the 5'- and the 3'-ends of the molecule, respectively. Phylogenetic analysis of the U2 sequences demonstrates remarkable conservation across species.

The Basques according to polymorphic Alu insertions.

Polymorphic Alu insertions provide a set of DNA markers of interest in human population genetics. Approximately 1000-2000 of these insertions have not reached fixation within the human genome. Each one of these polymorphic loci most probably resulted from a unique insertional event, and therefore all individuals possessing the insertion are related by descent not just state. In addition, the direction of mutational change is toward the gain of the Alu element at a particular locus. Therefore, the improved knowledge of both the ancestral state and the direction of mutational change greatly facilitates the analysis of population relationships. As a result, Alu insertion polymorphisms represent a significant tool for population genetic studies. In this study, polymorphic Alu insertions have been employed to ascertain phylogenetic relationships among Basque groups and worldwide populations. The Basques are considered to be a geographic isolate with a unique language and customs. They may be direct descendants of Cro-Magnon enclaves from the upper Paleolithic (38,000 to 10,000 years). The Basques are distributed among narrow valleys in northeastern Spain with little migration between them until recently. This characteristic may have had an effect on allelic frequency distributions. With the aim of studying this possible effect, we have analyzed six autosomal polymorphic Alu loci from four different sites within the Spanish Basque region in order to ascertain any genetic heterogeneity among the Basques. The results are consistent with a lack of homogeneity among these four autochthonous Basque groups.

Distribution of HLA-DQA1, polymarker, CSF1PO, vWA, TH01, TPOX, D16S539, D7S820, D13S317, and D5S818 alleles in East Bengali and West Punjabi populations from Indo-Pak Subcontinent.

Blood samples were collected from 115 individuals residing in the Pakistani state of West Punjab and 81 Bengali individuals residing in the state of East Bengal, India. These samples were analyzed for the loci HLA-DQA1, PM (LDLR, GYPA, HBGG, D7S8, and GC) and eight short tandem repeats: CSF1PO, TPOX, THO1, vWA, D16S539, D7S820, D13S317, and D5S818. Departures from Hardy-Weinberg (HWE) were observed in Punjabi population at LDLR, THO1, D13S317, D5S818, and D16S539 and at CSF1PO and THO1 in Bengali population.

Alu elements and the human genome.

Alu insertional elements, the most abundant class of SINEs in humans are dimeric sequences approximately 300 bp in length derived from the 7SL RNA gene. These sequences contain a bipartite RNA pol III promoter, a central poly A tract, a 3' poly A tail, numerous CpG islands and are bracketed by short direct repeats. An estimated 500,000 to 1 x 10(6) units are dispersed throughout the human haploid genome primarily in AT rich neighborhoods located within larger GC dense chromosomal regions via a mechanism known as retroposition. Retroposition activity of Alu elements is determined by both internal and flanking regulatory elements as well as distant genes affecting transcription or transcript stability. Alu elements impact the organization and expression of the human genome at many levels including the processes of recombination, transcription and translation. Twelve subfamilies of Alu are defined by distinct patterns of diagnostic base substitutions. Subfamilies may be classified as young, intermediate or old reflecting the time since the start of retroposition by their members. Some insertions of the youngest subfamilies are not yet fixed in the human species and represent polymorphic loci. Alus are excellent molecular markers for a variety of reasons. They aid in tracing the complex pattern of duplication and rearrangements that occurred during the evolution of primate genome. Unlike other mutations, Alu sequences are rarely lost completely once retroposed, have a defined ancestral state and are free from homoplasy since independent and identical insertions are highly unlikely. Because of these characteristics, Alus are literally molecular fossils. Polymorphic Alu loci are especially useful in studies of human genetic diversity and in pedigree and forensic analysis.

Phylogenetic signals from point mutations and polymorphic Alu insertions.

Allelic frequency data derived from five polymorphic Alu insertion loci and five point mutation polymorphic loci were compared to determine their ability to infer phylogenetic relationships among human populations. While point mutation polymorphisms inferred a monophyletic Caucasian clade that is corroborated by other studies, these data failed to support the generally accepted monophyly of Orientals with native Americans. In addition, there is less statistical bootstrap support for the maximum-likelihood tree derived from the point mutation polymorphisms as compared to those generated from either the Alu insertion data or the combined Alu insertion + point mutation data. The Alu data and the combined Alu insertion + point mutation data inferred a monophyletic relationship among the Oriental and native American populations. The Alu insertion data and the combined Alu insertion + point mutation data also displayed two separate, well defined, tight clusters of the Caucasian and the Oriental + native American populations which was not inferred from the point mutation data. These findings indicate greater phylogenetic information contained in Alu insertion frequencies than in allelic frequencies derived from point-mutations.

Inter- and intrapopulation studies of ancient humans.

For a genetic analysis of ancient human populations to be useful, it must be demonstrated that the DNA samples under investigation represent a single human population. Toward that end, we have analyzed human DNA from the Windover site (7000-8000 BP). MHC-I analysis, using allele-specific oligonucleotide hybridization to PCR amplified Windover DNA, microsatellite analysis by PCR of the APO-A2 repeat and mtD-loop 3' region sequencing on multiple individuals spanning nearly the full range of estimated burial dates all confirm the hypothesis that there is a persistence of both nuclear and mitochondrial haplotypes at Windover throughout its entire period of use. Thus, Windover can be considered a single population. Neighbor-joining tree analysis of mtDNA sequences suggests that some mitochondrial types are clearly related to extant Amerind types, whereas others, more distantly related, may reflect genetically distinct origins. A more complete sequence analysis will be required to firmly resolve this issue. Calibrating genetic relationships deduced by tree analysis, radiocarbon dates and burial position, yields a human mtD-loop DNA rate of evolution of 3700 to 14,000 years per percent change. Both values are within the range of recent, independently calculated values using estimates of evolutionary divergence or theoretical population genetics. Thus we are beginning to realize the promise of ancient DNA analysis to experimentally answer heretofore unapproachable questions regarding human prehistory and genetic change.