Twenty-seven microsatellite loci were used to define genetic variation and relationships among eight Indian riverine buffalo breeds. The total number of alleles ranged from 166 in the Toda breed to 194 each in the Mehsana and the Murrah. Significant departures from the Hardy-Weinberg equilibrium were observed for 26 locus-breed combinations due to heterozygote deficiency. Breed differentiation was analysed by estimation of F(ST) index (values ranging from 0.75% to 6.00%) for various breed combinations. The neighbour-joining tree constructed from chord distances, multidimensional scaling (MDS) display of F(ST) values and Bayesian clustering approach consistently identified the Toda, Jaffarabadi, and Pandharpuri breeds as one lineage each, and the Bhadawari, Nagpuri, Surati, Mehsana and Murrah breeds as admixture. Analysis of molecular variance refuted the earlier classification of these breeds proposed on the basis of morphological and geographical parameters. The Toda buffaloes, reared by a tribe of the same name, represent an endangered breed from the Nilgiri hills in South India. Divergence time of the Toda buffaloes from the other main breeds, calculated from Nei's standard genetic distances based on genotyping data on seven breeds and 20 microsatellite loci, suggested separation of this breed approximately 1800-2700 years ago. The results of the present study will be useful for development of rational breeding and conservation strategies for Indian buffaloes.

Key Points• Inositol hexakisphosphate kinase 1 (IP6K1) knockout mice display lower inorganic polyphosphate levels in platelets.• Low platelet polyphosphate leads to lengthened clotting time, altered clot architecture, and protection against pulmonary thromboembolism.Polyphosphate (polyP), a polymer of orthophosphate moieties released from the dense granules of activated platelets, is a procoagulant agent. Inositol pyrophosphates, another group of phosphate-rich molecules, consist of mono-and diphosphates substituted on an inositol ring. Diphosphoinositol pentakisphosphate (IP 7 ), the most abundant inositol pyrophosphate, is synthesized on phosphorylation of inositol hexakisphosphate (IP 6 ) by IP 6 kinases, of which there are 3 mammalian isoforms (IP6K1/2/3) and a single yeast isoform. Yeast lacking IP 6 kinase are devoid of polyP, suggesting a role for IP 6 kinase in maintaining polyP levels. We theorized that the molecular link between IP 6 kinase and polyP is conserved in mammals and investigated whether polyP-dependent platelet function is altered in IP6K1 knockout (Ip6k1) mice. We observe a significant reduction in platelet polyP levels in Ip6k1 2/2 mice, along with slower platelet aggregation and lengthened plasma clotting time. Incorporation of polyP into fibrin clots was reduced in Ip6k1 2/2 mice, thereby altering clot ultrastructure, which was rescued on the addition of exogenous polyP. In vivo assays revealed longer tail bleeding time and resistance to thromboembolism in Ip6k1 2/2 mice. Taken together, our data suggest a novel role for IP6K1 in regulation of mammalian hemostasis via its control of platelet polyP levels.

Water buffalo (Bubalus bubalis) is broadly classified into river and swamp categories, but it remains disputed whether these two types were independently domesticated, or if they are the result of a single domestication event. In this study, we sequenced the mitochondrial D-loop region and cytochrome b gene of 217 and 80 buffalo respectively from eight breeds/locations in northern, north-western, central and southern India and compared our results with published Mediterranean and swamp buffalo sequences. Using these data, river and swamp buffalo were distinguished into two distinct clades. Based upon the existing knowledge of cytogenetic, ecological and phenotypic parameters, molecular data and present-day distribution of the river and swamp buffalo, we suggest that these two types were domesticated independently, and that classification of the river and swamp buffalo as two related subspecies is more appropriate.

Background: The recently constructed river buffalo whole-genome radiation hybrid panel (BBURH 5000 ) has already been used to generate preliminary radiation hybrid (RH) maps for several chromosomes, and buffalo-bovine comparative chromosome maps have been constructed. Here,

More people globally depend on the water buffalo than any other domesticated species, and as the most closely related domesticated species to cattle they can provide important insights into the shared evolutionary basis of domestication. Here, we sequence the genomes of 79 water buffalo across seven breeds and compare patterns of between breed selective sweeps with those seen for 294 cattle genomes representing 13 global breeds. The genomic regions under selection between cattle breeds significantly overlap regions linked to stature in human genetic studies, with a disproportionate number of these loci also shown to be under selection between water buffalo breeds. Investigation of potential functional variants in the water buffalo genome identifies a rare example of convergent domestication down to the same mutation having independently occurred and been selected for across domesticated species. Cross-species comparisons of recent selective sweeps can consequently help identify and refine important loci linked to domestication.