Integrating Ancient and Modern DNA To Study Human History in South Asia and the Americas

Abstract

In the last two decades, advances in next-generation sequencing, genome-wide genotyping arrays, and methods to obtain DNA from ancient individuals have propelled the field of population genetics such that it is now an extraordinarily powerful tool for inferring human history. This thesis focuses on the study of DNA from both present-day and ancient individuals who existed between 50 to over 10,000 years ago. The analyses focus on South Asian, African-American, and Native American history and some applications of these historical insights for improving human health. Chapter 1.1 provides a background to the field, including a survey of the current methods for obtaining DNA from ancient individuals, the major statistical techniques for using genetics to infer human history, and past ways that archaeological and linguistic information have been integrated with genetics to arrive at more robust, contextualized models of the past. Chapter 1.2 provides a philosophical framework for conducting ethically-responsible genetics research in non-Western cultural contexts with a focus on South Asian and Native American groups. This ethical framework forms the groundwork for the studies in this thesis, and each subsequent section is introduced with a statement on how the study’s approach fits into this framework. Chapter 2 details a study on over 260 distinct present-day South Asian groups, demonstrating that 81 of these groups, including 14 with estimated census sizes over one million, descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. These founder events are population bottlenecks that can be detected on the basis of identity-by-descent (IBD) segments shared within the last 100 generations from a common founder, and they highlight an underappreciated opportunity for recessive disease-associated gene mapping in South Asia. Chapter 3 is an admixture mapping study that examines the increased European ancestry at chromosome 1 of African-Americans with Multiple Sclerosis (MS) relative to those without the disease and determines that the signal is due to two genetic variants within the CD58 and FCRL3 genes that together predict a 1.44-fold greater risk for MS in European-Americans compared to African-Africans. Chapter 4 introduces a new software, ContamLD, for estimating contamination in autosomal ancient DNA (aDNA) by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the contaminant DNA. Chapter 5 primarily focuses on three aDNA studies of Central and South America. The first study explores the earliest migrations into Central and South America from 11,000 to 4,000 years ago, while the next two studies focus on the changes in genetic structure over time in the Andes and Patagonia, including genetic analysis of individuals from major Andean cultures, such as the Wari, Tiwanaku, and Inca, as well as ancient individuals from the regions associated with the major Patagonian groups found at the time of European contact with representation of both maritime and terrestrial diet groups. Chapter 6 ties together the insights learned in these studies and compares them to findings of other world regions, highlighting surprising similarities and differences. Overall, this thesis presents just a small snapshot of the power of population genetics for inferring human history and how these insights can sometimes be used in unique ways to advance human health.