Project description:The genetic structure of the indigenous hunter-gatherer peoples of Southern Africa, the oldest known lineage of modern man, holds an important key to understanding humanity's early history. Previously sequenced human genomes have been limited to recently diverged populations. Here we present the first complete genome sequences of an indigenous hunter-gatherer from the Kalahari Desert and of a Bantu from Southern Africa, as well as protein-coding regions from an additional three hunter-gatherers from disparate regions of the Kalahari. We characterize the extent of whole-genome and exome diversity among the five men, reporting 1.3 million novel DNA differences genome-wide, and 13,146 novel amino-acid variants. These data allow genetic relationships among Southern African foragers and neighboring agriculturalists to be traced more accurately than was previously possible. Adding the described variants to current databases will facilitate inclusion of Southern Africans in medical research efforts.
Project description:The shift from a hunter-gatherer (HG) to an agricultural (AG) mode of subsistence is believed to have been associated with profound changes in the burden and diversity of pathogens across human populations. Yet, the extent to which the advent of agriculture impacted the evolution of the human immune system remains unknown. Here we present a comparative study of variation in the transcriptional responses of peripheral blood mononuclear cells (PBMCs) to bacterial and viral stimuli between the Batwa, a rainforest hunter-gatherer, and the Bakiga, an agriculturalist population from Central Africa. We observed increased divergence between hunter-gatherers and farmers in the transcriptional response to viruses compared to that for bacterial stimuli. We demonstrate that a significant fraction of these transcriptional differences are under genetic control, and we show that positive natural selection has helped to shape population differences in immune regulation. Unexpectedly, we found stronger signatures of recent natural selection in the rainforest hunter-gatherers, which argues against the popularized notion that shifts in pathogen exposure due to the advent of agriculture imposed radically heightened selective pressures in agriculturalist populations.
Project description:We utilized ChIP Seq to examine the the genomic localization of the increase in H3K9 trimethylation we had previously observed in the hippocampus as a consequence of acute restraint stress in rats (Hunter et. al PNAS 2009).
Project description:Background: The shells of various Haliotis species have served as models of invertebrate biomineralization and physical shell properties for more than 20 years. A focus of this research has been the nacreous inner layer of the shell with its conspicuous arrangement of aragonite platelets, resembling in cross-section a brick-and-mortar wall. In comparison, the outer, less stable, calcitic prismatic layer has received much less attention. One of the first molluscan shell proteins to be characterized at the molecular level was Lustrin A, a component of the nacreous organic matrix of Haliotis rufescens. This was soon followed by the C-type lectin perlucin and the growth factor-binding perlustrin, both isolated from H. laevigata nacre, and the crystal growth-modulating AP7 and AP24, isolated from H. rufescens nacre. Mass spectrometry-based proteomics was subsequently applied to to Haliotis biomineralization research with the analysis of the H. asinina shell matrix and yielded 14 different shell-associated proteins. That study was the most comprehensive for a Haliotis species to date. Methods: The shell proteomes of nacre and prismatic layer of the marine gastropod Haliotis laevigata were analyzed combining mass spectrometry-based proteomics and next generation sequencing. Results: We identified 297 proteins from the nacreous shell layer and 350 proteins from the prismatic shell layer from the green lip abalone H. laevigata. Considering the overlap between the two sets we identified a total of 448 proteins. Fifty-one nacre proteins and 43 prismatic layer proteins were defined as major proteins based on their abundance at more than 0.2% of the total. The remaining proteins occurred at low abundance and may not play any significant role in shell fabrication. The overlap of major proteins between the two shell layers was 17, amounting to a total of 77 major proteins. Conclusions: The H. laevigata shell proteome shares moderate sequence similarity at the protein level with other gastropod, bivalve and more distantly related invertebrate biomineralising proteomes. Features conserved in H. laevigata and other molluscan shell proteomes include short repetitive sequences of low complexity predicted to lack intrinsic three-dimensional structure, and domains such as tyrosinase, chitin-binding, and carbonic anhydrase. This catalogue of H. laevigata shell proteins represents the most comprehensive for a haliotid and should support future efforts to elucidate the molecular mechanisms of shell assembly.
Project description:ChIP-seq analysis of SNAIL binding sites in RH30 cells was performed to discover novel SNAIL binding sites in rhabdmyosarcoma cells.