Sooty Mangabey Genome Sequence Provides Insight into AIDS Resistance in a Natural SIV Host

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3-4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant leads to reduced cell surface expression of ICAM-2. These data provide a resource for comparative genomic studies of HIV and/or SIV pathogenesis and may help to elucidate the mechanisms by which SIV-infected sooty mangabeys avoid AIDS

Anthropological and Genetic History of Ethnic Groups in Mongolia

The ethnic groups that inhabit the present-day country of Mongolia have a complicated demographic history that has involved several waves of migration of different peoples at different times, especially over the past ten to twenty millennia. The genetic variation in contemporary populations in Mongolia has not been extensively studied. Adding to the interest in genetic studies in Mongolia, previous research has suggested that Mongolia may be a source of the founding population for the New World. However, few results have confirmed this hypothesis. Moreover, the genetic contribution of Mongolians to the gene pools of contemporary populations in Southeast Asia and Oceania has also not been extensively examined. Research on the genetic affinities of Mongolian ethnic groups remains scarce, and the impact of genetic admixture of ethnic groups of exogenous origins is not known. We review the history and demography of Mongolia as well as the genetic studies that relate to understanding variation within the contemporary ethnic groups of Mongolia. Future studies should concentrate on analyzing Y-chromosome variation as to enrich the results from some of the studies performed on mtDNA variation within Mongolia. They should also seek to determine the possible genetic contributions of the ancient Mongolian inhabitants' participation in the settlement of the New World, as well as their genetic contribution to the gene pools of modem populations of Southeast Asia and Oceania. To clarify the complex population history of Mongolia, variation in the mtDNAs of 190 individuals from several Mongolian ethnic groups was analyzed. We used PCR-RFLP analysis to type for coding region SNPs and HVR-I sequencing to assess control region variation in these groups. The resulting data provide insights into the origins and affinities of these populations with East Asian groups, their relationships to neighboring Turkic speaking groups, including indigenous Altaians, and their possible role in the peopling of the Americas

TAS2R38 (Phenylthiocarbamide) Haplotypes in Altaian Populations from South-Central Siberia

Over 70 years ago, it was reported that humans vary in taste sensitivity to the bitter compound phenylthiocarbamide (PTC). The inability to taste PTC is a classic phenotype that has long been assumed to be attributed to the recessive allele in a one-locus, two-allele system. PTC perception has been recognized to vary in all human populations to date. This variability is mainly controlled by the segregation of two common alleles at the TAS2R38 locus on chromosome 7, which encode receptor variants with different ligand affinities. The human TAS2R38 gene has been shown to occur in six haplotypic forms, although only two of these,\ud PAV and AVI, respectively, are associated with the major taster and non-taster phenotypes that have been observed in every population tested to date. This pattern of variation suggests that natural selection may have favored TAS2R38 alleles that are responsive to toxic, bitter phytochemical compounds naturally found in the environment. However, there is relatively little information about tasting gene variation in northern Asian populations. Therefore, to better understand patterns of tasting abilities in this region, we analyzed variation at the TAS2R38 locus in a sample of 253 individuals from indigenous Northern Altaian populations and 187 individuals from Southern Altaian populations in south-central Siberia. We screened the samples for two informative SNPs within the TAS2R38 gene using TaqMan assays that generate taster and non-taster phenotypes. Our data revealed a mixture of haplotypes related to differential tasting ability, as well as previously unrecognized haplotypes in these indigenous groups. We discuss the implications of these data for the genetic relationships of native Altaian populations with other modern human groups, and the possible effects of geographic isolation and adaptation on the patterns of allelic variation seen in south-central Siberia

The role of alternative splicing in primate genome evolution

We present the first pipeline to systematically identify and measure changes in Ψ in alternative splicing events across different genomes without annotation. Our method identified ~15,000 one-to-one orthologous alternative splicing events across human and 4 non-human primates. We show that alternative splicing events are increasing in abundance in every human tissue relative to non-human primates. Additionally, contrary to the tissue-dominated conservation pattern of gene expression, we show that most tissues except for brain, heart, and muscle, have a species-specific splicing pattern. Using these orthologous events, we identified 3,954 significant differential splicing events in 1,807 genes between humans and non-human primates. This thesis represents is part of the ambitious goal towards quantifying all of the changes in genomic complexity that occur between primate species. We provide evidence that these changes could be part of the "missing" genomic basis for the origin of human-specific traits

AncestralClust: Clustering of Divergent Nucleotide Sequences by Ancestral Sequence Reconstruction using Phylogenetic Trees.

MotivationClustering is a fundamental task in the analysis of nucleotide sequences. Despite the exponential increase in the size of sequence databases of homologous genes, few methods exist to cluster divergent sequences. Traditional clustering methods have mostly focused on optimizing high speed clustering of highly similar sequences. We develop a phylogenetic clustering method which infers ancestral sequences for a set of initial clusters and then uses a greedy algorithm to cluster sequences.ResultsWe describe a clustering program AncestralClust, which is developed for clustering divergent sequences. We compare this method with other state-of-the-art clustering methods using datasets of homologous sequences from different species. We show that, in divergent datasets, AncestralClust has higher accuracy and more even cluster sizes than current popular methods.Availability and implementationAncestralClust is an Open Source program available at https://github.com/lpipes/ancestralclust.Supplementary informationSupplementary figures and table are available online