Genome-wide patterns of selection in 230 ancient Eurasians

Ancient DNA makes it possible to directly witness natural selection by analyzing samples from populations before, during and after adaptation events. Here we report the first scan for selection using ancient DNA, capitalizing on the largest genome-wide dataset yet assembled: 230 West Eurasians dating to between 6500 and 1000 BCE, including 163 with newly reported data. The new samples include the first genome-wide data from the Anatolian Neolithic culture whose genetic material we extracted from the DNA-rich petrous bone and who we show were members of the population that was the source of Europe’s first farmers. We also report a complete transect of the steppe region in Samara between 5500 and 1200 BCE that allows us to recognize admixture from at least two external sources into steppe populations during this period. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height

Methylation of HPV16 and EPB41L3 in oral gargles and the detection of early and late oropharyngeal cancer

As oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) increases in men, the need for a screening test to diagnose OPC early is crucial. While HPV‐associated OPC has a favorable prognosis, recurrence is likely, and metastatic OPC is often incurable regardless of HPV status. Our previous study of pretreatment, male OPC cases (n = 101) and age‐ and smoking‐matched controls (n = 101) found methylation of the host EPB41L3 tumor suppressor gene and HPV16 in the oral gargle was correlated with these biomarkers in the tumor. Methylation of these genes in the oral gargle was significantly (p < 0.0001) higher among cases compared to controls. To further study the utility of HPV16/EPB41L3 methylation, we expanded the sample size and specifically increased the number of early OPC cases (T1‐T2, N0‐N1; small tumors with a single ipsilateral node <3 cm) to evaluate these biomarkers in early and late OPC. This study included 228 OPC cases, 92 of which were early cases and frequency matched to 142 healthy controls. In logistic regression, the AUC for HPV16/EPB41L3 methylation for all OPC cases was 0.82. Among early and late OPC cases, the AUC was 0.78 and 0.85, respectively. For early cases, 76% sensitivity was achieved, replicating results from our prior study, with a specificity of 65%, indicating room for improvement. The ability of HPV16/EPB41L3 methylation to distinguish OPC from healthy controls highlights its utility as a potential biomarker for OPC. However, the inability to predict early OPC better than late stage OPC indicates the need for additional biomarkers to improve screening performance

Methylation of HPV 16 and EPB41L3 in oral gargles: Associations with oropharyngeal cancer detection and tumor characteristics

Merck Investigator Initiated Studies Progra

Differential DNA methylation of vocal and facial anatomy genes in modern humans

Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and experimentally measured DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that likely emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes associated with face and vocal tract anatomy went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-associated 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.TMB is supported by BFU2017-86471-P (MINECO/FEDER, UE), U01 MH106874 grant, Howard Hughes International Early Career, Obra Social “La Caixa” and Secretaria d’Universitats i Recerca and CERCA Program del Departament d’Economia i Coneixement de la Generalitat de Catalunya. D.R. is an Investigator of the Howard Hughes Medical Institute and is also supported by an Allen Discovery Center for the Study of Human Brain Evolution funded the Paul G. Allen Family Foundation. C.L.-F. is supported by FEDER and BFU2015-64699-P grant from the Spanish government. R.P. was supported by ERC starting grant ADNABIOARC (263441). R.M.G. and J.M.O. are supported by NYSTEM contract C030133. Funding for the collection and processing of the 850K chimpanzee data was provided by the Leakey Foundation Research Grant for Doctoral Students, Wenner-Gren Foundation Dissertation Fieldwork Grant (Gr. 9310), James F. Nacey Fellowship from the Nacey Maggioncalda Foundation, International Primatological Society Research Grant, Sigma Xi Grant-in-Aid of Research, Center for Evolution and Medicine Venture Fund (ASU), Graduate Research and Support Program Grant (GPSA, ASU), and Graduate Student Research Grant (SHESC, ASU) to G.H. Collection of the chimpanzee bone from Tanzania was funded by the Jane Goodall Institute, and grants from the US National Institutes of Health (AI 058715) and National Science Foundation (IOS-1052693), and facilitated by Elizabeth Lonsdorf and Beatrice Hahn

Ethical challenges of working with archaeological human remains, with a focus on the UK

This chapter focuses on the ethical and practical considerations concerning archaeological human remains in the UK. It first contextualises the chapter by including a personal perspective of the author’s experience as a bioarchaeologist over the last 35 years in the UK. It then reflects upon the development of bioarchaeology in the UK, and its value in informing us about our past, and its rise from a “cottage industry” to a thriving area of archaeology. It then considers the guidance available for excavation, analysis, curation, and display of archaeological human remains in the UK, and makes recommendations for the future. These include having more open dialogue amongst all stakeholders, treating human remains with dignity and respect and not objectifying them, educating the public and students alike, especially in the case of destructive analyses, and debating who has the right to decide the “fate” of human remains. It further highlights areas of concern and emphasises the responsibility of all stakeholders to ensure appropriate care for our ancestors’ remains. Bioarchaeologists in particular have a duty to do their best for all human remains that have been, and will be, excavated and analysed in the future, and then curated, right across the world. We also have a duty to engage all stakeholders in debates, including the public and Indigenous people