Methods for Assessing Population Relationships and History Using Genomic Data

Genetic data contain a record of our evolutionary history. The availability of large-scale datasets of human populations from various geographic areas and timescales, coupled with advances in the computational methods to analyze these data, has transformed our ability to use genetic data to learn about our evolutionary past. Here, we review some of the widely used statistical methods to explore and characterize population relationships and history using genomic data. We describe the intuition behind commonly used approaches, their interpretation, and important limitations. For illustration, we apply some of these techniques to genome-wide autosomal data from 929 individuals representing 53 worldwide populations that are part of the Human Genome Diversity Project. Finally, we discuss the new frontiers in genomic methods to learn about population history. In sum, this review highlights the power (and limitations) of DNA to infer features of human evolutionary history, complementing the knowledge gleaned from other disciplines, such as archaeology, anthropology, and linguistics

Genetic Study of Population Mixture and Its Role in Human History

Mixture between populations is an evolutionary process that shapes genetic variation. Intermixing between groups of distinct ancestries creates mosaics of chromosomal segments inherited from multiple ancestral populations. Studying populations of mixed ancestry (admixed populations) is of special interest in population genetics as it not only provides insights into the history of admixed groups but also affords an opportunity to reconstruct the history of the ancestral populations, some of whom may no longer exist in unmixed form. Furthermore, it improves our understanding of the impact of population migrations and helps us discover links between genetic and phenotypic variation in structured populations. The majority of research on admixed populations has focused on African Americans and Latinos where the mixture is recent, having occurred within the past 500 years. In this dissertation, I describe several studies that I have led that expand the scope of admixed studies to West Eurasians and South Asians where the mixture is older, and data from ancestral groups is mostly unavailable. First, I introduce a novel method that studies admixture linkage disequilibrium (LD) to infer the time of mixture. I analyze genomewide data from 40 West Eurasian populations and show that all Southern European, Levantine and Jewish groups have inherited sub-Saharan African ancestry in the past 100 generations, likely reflecting events during the Roman Empire and subsequent Arab migrations. Next, I apply a range of methods to study the history of Siddi groups that harbor African, Indian and Portuguese ancestry, and to infer the history of Roma gypsies from Europe. Finally, I develop a novel approach that combines the insights of frequency and LD-based statistics to infer the underlying model of mixture. I apply this method to 73 South Asian groups and infer that major mixture occurred ~2,000-4,000 years ago. In a subset of populations, all the mixture occurred during this period, a time of major change in India marked by the de- urbanization of the Indus valley civilization and recolonization of the Gangetic plateau. Inferences from our analyses provide novel insights into the history of these populations as well as about the broad impact of human migrations

Variation in the molecular clock of primates

Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid–NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​.United States. National Institutes of Health (F32 GM115006-01

Reconstructing Austronesian population history in Island Southeast Asia

Austronesian languages are spread across half the globe, from Easter Island to Madagascar. Evidence from linguistics and archaeology indicates that the ‘Austronesian expansion,’ which began 4,000–5,000 years ago, likely had roots in Taiwan, but the ancestry of present-day Austronesian-speaking populations remains controversial. Here, we analyse genome-wide data from 56 populations using new methods for tracing ancestral gene flow, focusing primarily on Island Southeast Asia. We show that all sampled Austronesian groups harbour ancestry that is more closely related to aboriginal Taiwanese than to any present-day mainland population. Surprisingly, western Island Southeast Asian populations have also inherited ancestry from a source nested within the variation of present-day populations speaking Austro-Asiatic languages, which have historically been nearly exclusive to the mainland. Thus, either there was once a substantial Austro-Asiatic presence in Island Southeast Asia, or Austronesian speakers migrated to and through the mainland, admixing there before continuing to western Indonesia

Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium

Author Manuscript date February 9, 2013Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.National Science Foundation (U.S.). Graduate Research Fellowship ProgramNational Institutes of Health (U.S.). (Training Grant 5T32HG004947-04)Simons Foundatio

Association Between Episodic Memory and Genetic Risk Factors for Alzheimer’s Disease in South Asians from the Longitudinal Aging Study in India–Diagnostic Assessment of Dementia (LASI‐DAD)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156473/3/jgs16735-sup-0001-supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156473/2/jgs16735_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156473/1/jgs16735.pd