Project description:The project aimed to characterize the collagen type I (COL1) sequences from Pleistocene Macrauchenia sp. and Toxodon sp. bone samples, and by comparison with existing COL1 sequences available from genomic sources establish the phylogenetic position of both extinct species. In order to resolve their phylogenetic position, COL1 was extracted from two Toxodon (samples MLP201204, MACN201212, York12, York13) and two Macrauchenia (samples MLP201212, MACN201202, York14, York15). In addition, modern and Pleistocene COL1 was extracted from additional species currently not present in available databases (Mylodon darwinii, Cyclopes didactylus, Hippopotamus amphibius, Tapirus terrestris) or from species for which COL1 sequences are available (Equus sp., Oryceropus afer). All extractions were performed at BioArCh, University of York (UK). Analyses took place on Bruker maXis HD (Macrauchenia sp., Toxodon sp., Equus sp.) and Thermo Scientific Hybrid Quadruopole-Orbitrap (Macrauchenia sp., Toxodon sp., Mylodon darwinii, Cyclopes didactylus, Hippopotamus amphibius, Tapirus terrestris, Oryceropus afer) platforms.
Project description:East African cichlid fishes have diversified in an explosive fashion, but the (epi)genetic basis of the phenotypic diversity of these fishes remains largely unknown. Although transposable elements (TEs) have been associated with phenotypic variation in cichlids, little is known about their transcriptional activity and epigenetic silencing. Here, we describe dynamic patterns of TE expression in African cichlid gonads and during early development. Orthology inference revealed an expansion of piwil1 genes in Lake Malawi cichlids, likely driven by PiggyBac TEs. The expanded piwil1 copies have signatures of positive selection and retain amino acid residues essential for catalytic activity. Furthermore, the gonads of African cichlids express a Piwi-interacting RNA (piRNA) pathway that target TEs. We define the genomic sites of piRNA production in African cichlids and find divergence in closely related species, in line with fast evolution of piRNA-producing loci. Our findings suggest dynamic co-evolution of TEs and host silencing pathways in the African cichlid radiations. We propose that this co-evolution has contributed to cichlid genomic diversity.
Project description:Women of sub-Saharan African descent have disproportionately higher incidence of Triple Negative Breast Cancer (TNBC), and TNBC-specific mortality. Population comparative studies show racial differences in TNBC biology, including higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily United States (US) populations. Due to heterogenous genetic admixture, and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed tumor-associated immunological profiles are distinct in patients of African descent.