Project description:Glycoproteomics is likely to identify Mtb virulence factors because glycoproteins on the bacterial cell envelope are used by mycobacteria to enter the primary human host cell, the macrophage. It has been proposed that Mtb interacts with mannose receptors on host cells via mannosylated proteins to enter the macrophages. Despite the vital importance of these proteins in Mtb pathogenesis, our current knowledge of Mtb glycoproteins is still limited, and only a few secreted and cell wall-associated glycoproteins have to date been described. Previous studies have used laboratory strains as model systems to study glycosylation in Mtb. However, only a few sub-groups within the genetically conserved MTBC appear to cause extensive outbreaks with different clinical presentation and AMR. In this study, we employed qualitative and quantitative mass spectrometry and bioinformatics to explore the glycoproteomic patterns of clinical isolates from four lineages of the MTBC, lineages 3, 4, 5 and 7, to investigate the role of protein glycosylation in Mtb adaptation, survival and AMR.
Project description:The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ~2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations at least 100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa, instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history .220 samples were analysed with the Illumina HumanOmni2.5-Quad BeadChip and are described herein.
Project description:A major challenge in biology is to determine how evolutionarily novel characters originate, however, mechanistic explanations for the origin of novelties are almost completely unknown. The evolution of mammalianM-BM- pregnancy is an excellent system in which to study the origin of novelties because extant mammals preserve major stages in the transition from egg-laying to live-birth. To determine the molecular bases of this transition we characterized the pregnant/gravid uterine transcriptome from tetrapods, including species in the three major mammalian lineages, and used ancestral transcriptome reconstruction to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including numerous genes that mediate maternal-fetal communication and immunotolerance.Furthermore we show that thousands of regulatory elements active inM-BM- decidualized human endometrial stromal cellsM-BM- are derived from ancient mammalian transposable elements which provided binding sites for transcription factors that mediate decidualization and endometrial cell-type identity.M-BM- Our results indicate that one of the defining mammalian novelties evolved via domestication of ancient mammalian transposable elements into hormone-responsive regulatory elements throughout the genome. Examination of histone modification and DNAse hypersensitivity in decidualized dESC
Project description:Long noncoding RNA sequences evolve relatively rapidly, but it is unclear whether this is due to relaxed constraint or accelerated evolution. Here, we trace the recent evolutionary history of human lncRNAs, using genomes of multiple individuals from all great ape species to map fixed lineage-specific nucleotide variants. We find that the lower conservation of lncRNAs compared to protein coding genes partially arises from lncRNA’s more recent evolutionary origin. We identify more than one hundred lncRNAs that show some evidence of accelerated evolution in at least one primate species, including 17 in human. Several of these display transcriptional regulatory activity in an RNA-specific reporter assay. By experimentally reconstructing the ancestral lncRNA sequence, we find that this activity has been altered by human-specific nucleotide substitutions. Functional analysis of accelerated lncRNAs with specific expression in blood suggests lncRNAs have participated in adaptive regulatory changes in the immune system during recent human evolution. Together our results provide evidence that accelerated evolution of lncRNAs may have contributed, through regulatory changes, to human-specific phenotypes.