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Research

Overview

The lab’s research interests are within the field of human and non-human primate population and evolutionary genetics. We are primarily an empirical lab that is interested in using genetic data in model-testing frameworks to elucidate key parameters characterizing the evolution of anatomically modern humans. Disentangling the complex and intertwined roles of demographic history and natural selection in shaping patterns of genetic/genomic variation in humans—as well as the other hominins and non-human primates species from which we are most recently diverged—is a key aspect of this inference process.

Primate Comparative Genomics

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One of the most effective ways of understanding the evolution of the human genome is to compare it to those of other species, in particular apes and other phylogenetically more distant primates such as baboons or lemurs. Such comparisons can also inform us about the exact mechanisms of evolution, while understanding the genetic basis for tree-swinging in gibbons or why chimpanzees, but not gorillas, can eat KFC chicken is fascinating in its own right. We are interested in developing and applying quantitative genetics methods to whole genome data in order to better understand demographic and evolutionary processes in a range of primate species. In particular we are interested in (a) understanding how the evolution of the autosomes and X-chromosomes has been affected by features such as higher variance in male reproductive success, sex-biased migration, different efficiencies of positive/negative selection and opposing forces of selection on males and females, (b) understanding how mutation and recombination rates observed in modern humans compare to other primates species who vary in effective population size, body size and generation time and (c) developing methods for inferring demographic history and natural selection that account of geographical/demic sampling biases so often present amongst DNA samples from wild born apes.

Three-spined stickleback genomics

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We traditionally envision adaptation of organisms to new environments as starting with appearance of a new favorable mutation and spreading to the population. While this view applies well to microbes, such as yeast or bacteria, it usually takes much longer for new mutations to arise and spread in large-bodied, less-abundant species, and when they do, they are more likely to be lost. An alternative view for adaptation that may apply well to humans is emerging; many mutations persist in populations for a long time as “standing genetic variation” (SGV) even though they have weak or even adverse effects on chances to survive and reproduce (i.e., natural selection). When an environment changes or people migrate, variants in the SGV may become highly advantageous, allowing the population to adapt quickly to its new surroundings. There is growing evidence that SGV is crucial for adaptation of many species over short time scales. However, while examples of adaptation based on SGV are growing, surprisingly little is known, either theoretically or empirically, about the evolutionary dynamics of adaptation based on this mechanism. In the last five years, the Threespine Stickleback (TS, Gasterost eus aculeatus) fish has emerged as the premier subject to study adaptation based on SGV. Sea-run stickleback contain abundant SGV and have repeatedly invaded fresh water. Much of their adaptation to fresh water occurs within a decade after they colonize it and depends on SGV. The overall goal of our research is to understand the evolutionary dynamics of adaptation based on SGV in TS. In collaboration with Professor Mike Bell (E&E Stony Brook), we are aiming to address such questions by characterizing genomic variation in ancestral anadromous TS populations as well as multiple Alaskan freshwater TS populations sampled at various time points starting immediately after the colonization of the lakes, allowing us to directly observe and model the dynamics of allele frequency evolution through time.

aDNA from Migration Period Europe

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Few topics in European history are as controversial and disputed as the barbarian migrations into the Roman world at the end of Antiquity (~400 AD). Historians have debated for centuries the magnitude, nature, and impact of the movement of populations from the borders of the Roman empire into its heart between the fifth and seventh centuries. For example were barbarian invasions or migrations the cause of the disintegration of the Roman Empire? How large and significant were these migrations? Did they replace local populations, simply dominate them, or rapidly merge with them? The traditional sources used by scholars to answer these and other questions regarding the period have been written sources and archaeological material. However, the development of 2nd generation sequencing over the past five years has led to a revolution in paleogenetics, allowing us to reliably extract whole genomes from hominin specimens tens of thousands of years old. Thus it should conceivably be feasible to extract aDNA from samples from the Migration Period era, which may reveal new information about this important period in European history. Therefore, led by historian Patrick Geary (Institute for Advanced Study, Princeton), we are part of an international project that will attempt to extract, sequence and analyze mitochondrial, Y chromosome and autosomal aDNA from ~800 Medieval specimens from Italy, Hungary and Austria collected through a network of European archaeologists. This data will be used to shed light on the proposed migration of the Langobards (also known as the Lombards), a Germanic people first identified as living along the shores of the Baltic Sea in the 1st century C.E but later established in Pannonia (what is now Western Hungary, the Czech Republic, and Eastern Austria) prior to their entry into Italy in 568, where they established a vast kingdom that lasted for ~200 years. We will utilize a multidisciplinary approach within a quantitative framework, with the aim of extending this project to other barbarian migrations from Migration Period Europe.

The Evolutionary Genetic Basis of Epilepsy

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2nd generation sequencing is having an enormous impact on the search for genes that underlie the genetic basis of neurological disorders. Pathogenic de novo variants are emerging as one of the main factors that cause epilepsy, particularly within ion channel genes. As an example, ~80% of children with Dravet Syndrome, a catastrophic childhood epilepsy associated with a variety of other debilitating problems such as severe intellectual disability and motor problems, appears to be caused de novo mutations in the voltage-gated sodium channel SCN1A, while more than 100 children with other severe childhood epilepsies have now been found to harbor mutations within SCN8A. However, while the protein structures are very similar, and both are expressed at high levels in the brain, SCN1A mutations tend to cause disease via loss of gene function, while SCN8A-based diseases are caused by gain-of-function mutations. We are interested in exploring the evolution of these key ion channels, and are characterizing both genetic and epigenetic variation across various taxa, in particular amongst primates