The Y-chromosome of the Soliga, an ancient forest-dwelling tribe of South India.

A previous autosomal STR study provided evidence of a connection between the ancient Soliga tribe at the southern tip of the Indian subcontinent and Australian aboriginal populations, possibly reflecting an eastbound coastal migration circa (15 Kya). The Soliga are considered to be among India's earliest inhabitants. In this investigation, we focus on the Y chromosomal characteristics shared between the Soliga population and other Indian tribes as well as western Eurasia and Sub-Saharan Africa groups. Some noteworthy findings of this present analysis include the following: The three most frequent haplogroups detected in the Soliga population are F*, H1 and J2. F*, the oldest (43 to 63 Kya), has a significant frequency bias in favor of Indian tribes versus castes. This observation coupled with the fact that Y-STR haplotypes shared with sub-Saharan African populations are found only in F* males of the Soliga, Irula and Kurumba may indicate a unique genetic connection between these Indian tribes and sub-Saharan Africans. In addition, our study suggests that haplogroup H is confined mostly to South Asia and immediate neighbors and the H1 network may indicate minimal sharing of Y-STR haplotypes among South Asian collections, tribal and otherwise. Also, J2, brought into India by Neolithic farmers, is present at a significantly higher frequency in caste versus tribal communities. This last observation may reflect the marginalization of Indian tribes to isolated regions not ideal for agriculture.

The Y-chromosome of the Soliga, an ancient forest-dwelling tribe of South India.

A previous autosomal STR study provided evidence of a connection between the ancient Soliga tribe at the southern tip of the Indian subcontinent and Australian aboriginal populations, possibly reflecting an eastbound coastal migration circa (15 Kya). The Soliga are considered to be among India's earliest inhabitants. In this investigation, we focus on the Y chromosomal characteristics shared between the Soliga population and other Indian tribes as well as western Eurasia and Sub-Saharan Africa groups. Some noteworthy findings of this present analysis include the following: The three most frequent haplogroups detected in the Soliga population are F*, H1 and J2. F*, the oldest (43 to 63 Kya), has a significant frequency bias in favor of Indian tribes versus castes. This observation coupled with the fact that Y-STR haplotypes shared with sub-Saharan African populations are found only in F* males of the Soliga, Irula and Kurumba may indicate a unique genetic connection between these Indian tribes and sub-Saharan Africans. In addition, our study suggests that haplogroup H is confined mostly to South Asia and immediate neighbors and the H1 network may indicate minimal sharing of Y-STR haplotypes among South Asian collections, tribal and otherwise. Also, J2, brought into India by Neolithic farmers, is present at a significantly higher frequency in caste versus tribal communities. This last observation may reflect the marginalization of Indian tribes to isolated regions not ideal for agriculture.

Investigating the genetic diversity and affinities of historical populations of Tibet.

This study elucidates Y chromosome distribution patterns in the three general provincial populations of historical Tibet, Amdo (n = 88), Dotoe (n = 109) and U-Tsang (n = 153) against the backdrop of 37 Asian reference populations. The central aim of this study is to investigate the genetic affinities of the three historical Tibetan populations among themselves and to neighboring populations. Y-SNP and Y-STR profiles were assessed in these historical populations. Correspondence analyses (CA) were generated with Y-SNP haplogroup data. Y-STR haplotypes were determined and employed to generate multidimensional scaling (MDS) plots based on Rst distances. Frequency contour maps of informative Y haplogroups were constructed to visualize the distributions of specific chromosome types. Network analyses based on Y-STR profiles of individuals under specific Y haplogroups were generated to examine the genetic heterogeneity among populations. Average gene diversity values and other parameters of population genetics interest were estimated to characterize the populations. The Y chromosomal results generated in this study indicate that using two sets of markers (Y-SNP, and Y-STR) the three Tibetan populations are genetically distinct. In addition, U-Tsang displays the highest gene diversity, followed by Amdo and Dotoe. The results of this transcontinental biogeographical investigation also indicate various degrees of paternal genetic affinities among these three Tibetan populations depending on the type of loci (Y-SNP or Y-STR) analyzed. The CA generated with Y-SNP haplogroup data demonstrates that Amdo and U-Tsang are closer to each other than to any neighboring non-Tibetan group. In contrast, the MDS plot based on Y-STR haplotypes displays Rst distances that are much shorter between U-Tsang and its geographic nearby populations of Ladakh, Punjab, Kathmandu and Newar than between it and Amdo. Moreover, although Dotoe is isolated from all other groups using both types of marker systems, it lies nearer to the other Tibetan collections in the Y-SNP CA than in the Y-STR MDS plot. High resolution and shallow evolutionary time frames engendered by Y-STR based analyses may reflect a more recent demographic history than that delineated by the more conserved Y-SNP markers.

Aptamers against Cells Overexpressing Glypican†3 from Expanded Genetic Systems Combined with Cell Engineering and Laboratory Evolution.

Laboratory in vitro evolution (LIVE) might deliver DNA aptamers that bind proteins expressed on the surface of cells. In this work, we used cell engineering to place glypican 3 (GPC3), a possible marker for liver cancer theranostics, on the surface of a liver cell line. Libraries were then built from a six-letter genetic alphabet containing the standard nucleobases and two added nucleobases (2-amino-8H-imidazo[1,2-a][1,3,5]triazin-4-one and 6-amino-5-nitropyridin-2-one), Watson-Crick complements from an artificially expanded genetic information system (AEGIS). With counterselection against non-engineered cells, eight AEGIS-containing aptamers were recovered. Five bound selectively to GPC3-overexpressing cells. This selection-counterselection scheme had acceptable statistics, notwithstanding the possibility that cells engineered to overexpress GPC3 might also express different off-target proteins. This is the first example of such a combination.

Y-STR markers from Ladakh in the Himalayas.

A total of 223 samples from the general population of Ladakh in Northwestern India were amplified at 17 Y-STR loci using the AmpFlSTR® Yfiler™ system. The DNA profiles generated were employed to generate allelic frequencies, gene diversity, haplotype diversity and discrimination capacity values as well as number of different haplotypes, fraction of unique haplotypes and Rst pair wise genetic distances. Multidimensional Scaling (MDS) and Correspondence Analysis (CA) were performed with the Rst values and allelic frequencies, respectively. The 17-loci discrimination capacity of Ladakh was found to be 0.8093. Eleven out of the 16 loci have diversity values greater than 0.6, and 13 loci possess values greater than 0.5. Ladakh exhibits no significant genetic difference to seven of the 15 reference forensic databases after Bonferroni correction, three of which are located in South Central Asian and four are from the Himalayan region. Rst genetic distance values before and after Bonferroni corrections illustrate the capacity of the Yfiler system to discriminate among Himalayan populations. The intermediate position of the Ladakh population in the MDS and CA plots likely reflects genetic flow and admixture with neighboring populations. In addition, the longitudinal partition of populations in the MDS and CA plots likely reflect human dispersals such as the silk road migrations.

Ladakh, India: the land of high passes and genetic heterogeneity reveals a confluence of migrations.

Owing to its geographic location near the longitudinal center of Asia, Ladakh, the land of high passes, has witnessed numerous demographic movements during the past millenniums of occupation. In an effort to view Ladakh's multicultural history from a paternal genetic perspective, we performed a high-resolution Y-chromosomal survey of Ladakh, within the context of Y haplogroup and haplotype distributions of 41 Asian reference populations. The results of this investigation highlight the rich ethnic and genetic diversity of Ladkah which includes genetic contributions from disparate regions of the continent including, West, East, South and Central Asia. The phylogenetic signals from Ladakh are consistent with the Indo-Aryans' occupation during the Neolithic age and its historic connection with Tibet, as well as the East-West gene flow associated with the Silk Road.

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance.

BACKGROUND: Many synthetic biologists seek to increase the degree of autonomy in the assembly of long DNA (L-DNA) constructs from short synthetic DNA fragments, which are today quite inexpensive because of automated solid-phase synthesis. However, the low information density of DNA built from just four nucleotide "letters", the presence of strong (G:C) and weak (A:T) nucleobase pairs, the non-canonical folded structures that compete with Watson-Crick pairing, and other features intrinsic to natural DNA, generally prevent the autonomous assembly of short single-stranded oligonucleotides greater than a dozen or so. RESULTS: We describe a new strategy to autonomously assemble L-DNA constructs from fragments of synthetic single-stranded DNA. This strategy uses an artificially expanded genetic information system (AEGIS) that adds nucleotides to the four (G, A, C, and T) found in standard DNA by shuffling hydrogen-bonding units on the nucleobases, all while retaining the overall Watson-Crick base-pairing geometry. The added information density allows larger numbers of synthetic fragments to self-assemble without off-target hybridization, hairpin formation, and non-canonical folding interactions. The AEGIS pairs are then converted into standard pairs to produce a fully natural L-DNA product. Here, we report the autonomous assembly of a gene encoding kanamycin resistance using this strategy. Synthetic fragments were built from a six-letter alphabet having two AEGIS components, 5-methyl-2'-deoxyisocytidine and 2'-deoxyisoguanosine (respectively S and B), at their overlapping ends. Gaps in the overlapped assembly were then filled in using DNA polymerases, and the nicks were sealed by ligase. The S:B pairs in the ligated construct were then converted to T:A pairs during PCR amplification. When cloned into a plasmid, the product was shown to make Escherichia coli resistant to kanamycin. A parallel study that attempted to assemble similarly sized genes with optimally designed standard nucleotides lacking AEGIS components gave successful assemblies of up to 16 fragments, but generally failed when larger autonomous assemblies were attempted. CONCLUSION: AEGIS nucleotides, by increasing the information density of DNA, allow larger numbers of DNA fragments to autonomously self-assemble into large DNA constructs. This technology can therefore increase the size of DNA constructs that might be used in synthetic biology.

Taiwanese aborigines: genetic heterogeneity and paternal contribution to Oceania.

In the present study, for the first time, 293 Taiwanese aboriginal males from all nine major tribes (Ami, Atayal, Bunun, Rukai, Paiwan, Saisat, Puyuma, Tsou, Yami) were genotyped with 17 YSTR loci in a attend to reveal migrational patterns connected with the Austronesian expansion. We investigate the paternal genetic relationships of these Taiwanese aborigines to 42 Asia-Pacific reference populations, geographically selected to reflect various locations within the Austronesian domain. The Tsou and Puyuma tribes exhibit the lowest (0.1851) and the highest (0.5453) average total genetic diversity, respectively. Further, the fraction of unique haplotypes is also relatively high in the Puyuma (86.7%) and low in Tsou (33.3%) suggesting different demographic histories. Multidimensional scaling (MDS) and analysis of molecular variance (AMOVA) revealed several notable findings: 1) the Taiwan indigenous populations are highly diverse. In fact, the level of inter-population heterogeneity displayed by the Taiwanese aboriginal populations is close to that exhibited among all 51 Asia-Pacific populations examined; 2) the asymmetrical contribution of the Taiwanese aborigines to the Oceanic groups. Ami, Bunun and Saisiyat tribes exhibit the strongest paternal links to the Solomon and Polynesian island communities, whereas most of the remaining Taiwanese aboriginal groups are more genetically distant to these Oceanic inhabitants; 3) the present YSTR analyses does not reveal a strong paternal affinity of the nine Taiwanese tribes to their continental Asian neighbors. Overall, our current findings suggest that, perhaps, only a few of the tribes were involved in the migration out of Taiwan.

Phylogenetic and forensic studies of the Southeast Florida Hispanic population using the next-generation forensic PowerPlex® Y23 STR marker system.

The purpose of this study is to examine the robustness and sensitivity of the newly available Y-STR multiplex kit, the PowerPlex® Y23 System, by comparing our data at the 23-loci level to the routinely used 17 loci provided by the AmpFlSTR® Yfiler® PCR Amplification kit. For the first time, allelic and genotypic frequencies for the 23 Y-STR loci included in the PowerPlex® Y23 System are provided for the Southeast Florida Hispanic (SFH) population. In addition, we have characterized the SFH population in terms of intra-population and inter-population parameters. We also compared these indices of forensic and population genetics interest in the SFH population to comparable data of previously published populations to assess their phylogenetic relationships. Our 23-loci data was shown to provide more discriminatory values as compared to the data when using only 17 loci. Also, the RST distance values demonstrate the superior capacity of the PowerPlex® Y23 system to discriminate among populations.

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.

On human STR sub-population structure.

This study is an investigation of genetic variation among the CODIS (combined DNA index system) STR (short tandem repeat) reference collections. The analysis was conducted in two parts. The first is an overall comparison (G-test) of allelic frequency distributions for 12 STR loci among 19 forensic databases representing various major groups and ethnic populations. In the second phase of the study, the impact of database replacement on DNA profile frequencies and inclusion probabilities is examined. The G-test results reveal clear allelic frequency differences among the major divisions, and, in some cases, among ethnically distinct subdivisions of the same major group affiliation. Other results indicate that database substitution may sometimes lead to substantial alterations in individual inclusion probabilities. Furthermore, there are numerous instances in which an allele present in some databases is missing in others. Fortunately, in most cases, these effects may not be forensically significant due to the increased discriminatory power of the STR markers employed in the CODIS system. However, differences in inclusion probabilities may become critical in situations in which DNA quantity is severely limited and/or compromised by degradation since, in these cases, the power of forensic STR analysis may be mitigated by reducing the number of informative loci.

Inferring recent human phylogenies using forensic STR technology.

STR loci are characterized by extremely high mutation rates and thus, high levels of length polymorphism both within and among populations. In addition, much of the observed variation is believed to be nearly selectively neutral. Because of these features, STRs are ideal markers for genetic mapping, intra-species phylogenetic reconstructions and forensic analysis. In the present study, we investigate the application of five STR loci (CS1PO, TH01, TPOX, FGA and vWA) routinely used in forensic analysis for delineating the phylogenetic relationships of 10 human populations representing the three major racial groups (African-Caribbean, Croatian from the island of Hvar, East Asian, Han Chinese, Italian, Japanese, Portuguese, UK Caucasian, US Caucasian and Zimbabwe). The resulting tree topology exhibited strong geographic and racial partitioning consistent with that obtained with mtDNA haplotypes, Y-chromosome markers, SNPs, PAIs (polymorphic Alu insertions) as well as classic genetic polymorphisms. These findings suggest that forensic STR loci may be particularly powerful tools and provide the necessary fine resolution for the reconstruction of recent human evolutionary history.

On the genetic uniqueness of the Ami aborigines of Formosa.

In the attempt to reconstruct the prehistory of Pacific and Indian Ocean populations, Taiwan's aborigines appear to be of particular interest. Linguistic and archeological evidence indicates that the dispersal of Austronesian speakers throughout the islands of Oceania and Southeast Asia may have originated from Taiwan about 5,000 years ago. The Ami are Taiwan's largest aboriginal group. Here, we report on six polymorphic point mutation loci in Ami individuals and compare allelic frequencies to worldwide populations. In order to examine the genetic characteristics and relationships of the Ami aborigines, we used the allelic frequency data to generate expected heterozygosities, power of discrimination values, maximum likelihood phylogenetic trees, principal component maps, and centroid gene flow plots. These analyses argue for the genetic isolation and uniqueness of the Ami people. Data supportive of limited gene flow and/or small population size, as well as genetic similarities to Native Americans, were observed.