Project description:How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we find that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (KYA), and after no more than 8,000-year isolation period in Beringia. Native Americans diversified into two basal genetic branches around 13 KYA, one in North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians and Australo-Melanesians, the latter possibly through the ancestors of Aleutian Islanders. Putative relict populations in South America, including the historical Pericúes and Fuego-Patagonians, are not directly related to modern Australo-Melanesians.
Project description:This study was designed to investigate the efficacy of flow cytometry to accurately identify between normal and cancer cells in colon epithelium in humans diagnosed with colorectal cancer.
Project description:Regulatory changes are broadly accepted as key drivers of phenotypic divergence. However, identifying regulatory changes that underlie human-specific traits has proven very challenging. Here, we use 63 DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes affecting the face and vocal tract went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-affecting genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract
Project description:The Neanderthal and Denisovan genomes enabled the discovery of sequences that differ between modern and archaic humans, the majority of which are noncoding. However, our understanding of the regulatory consequences of these differences remains limited, in part due to the decay of regulatory marks in ancient samples. Here, we used a massively parallel reporter assay in embryonic stem cells, neural progenitor cells and bone osteoblasts to investigate the regulatory effects of the 14,042 single-nucleotide modern human-specific variants. Overall, 1,791 (13%) of sequences containing these variants showed active regulatory activity, and 407 (23%) of these drove differential expression between human groups. Differentially active sequences were associated with divergent transcription factor binding motifs, and with genes enriched for vocal tract and brain anatomy and function. This work provides insight into the regulatory function of variants that emerged along the modern human lineage and the recent evolution of human gene expression.
Project description:Detailed investigation of extremely severe pathological conditions present in ancient human skeletons is important because they can illuminate the breadth of potential interactions between humans and disease etiologies in the past. Here, we applied palaeoproteomics to investigate the bacterial pathogenic factors and host defense response to an ancient human skeletal individual with severe oral pathology. This female skeleton, from the Okhotsk period (i.e., 5th–13th century) of northern Japan, poses abnormal deposition of large amounts of dental calculus and oral dysfunction due to severe periodontal disease. A shotgun mass-spectrometry analysis identified 81 human proteins and 15 bacterial proteins from her calculus. Two pathogenic or bio-invasive proteins originating from two of the three “red complex” bacteria, the core species associated with severe periodontal disease in modern humans, as well as additional two bio-invasive proteins of periodont-associated bacteria were identified. Human proteins associated with the defense response system were identified, but their proportion was mostly similar to that reported in ancient and modern human individuals with lower calculus deposition. These results suggest that the bacterial etiology was similar and the host defense response was not necessarily higher in ancient individuals with abnormal deposition of large amounts of dental calculus.