David Reich is interested in interested in human history and its relationship to biology. His lab takes advantage of the revolution in gene sequencing that has occurred in the last decade, along with new technology to sequence DNA extracted from ancient bones. The historical perspective that he brings to genetic data has led to a number of new insights about human biology and disease.
The laboratory focuses on three areas, all of which capitalize on the historical perspective to learn about human biology.
Using the Historical Perspective to Improve Human Health
A major focus of our laboraotry has been to search for risk factors for disease that occur at very different frequencies across populations. For example, we found seven genetic risk factors for prostate cancer that are sufficient to explain the elevated rate of this disease in African Americans. A current project is motivated by the fact that thousands of groups in India have experienced founder events as strong as those that have occurred in Ashkenazi Jews or Finns. This predicts that there will be many rare recessive diseases in India. Mapping and understanding these diseases should provide a major opportunity for public health improvement as well as a natural laboratory in which to study genetic disease. With our collaborator Kumarasamy Thangaraj at the Center for Cellular and Molecular Biology, Hyderabad, India, we are genetically surveying many groups and exploring which are most likely to be most susceptible to recessive disease (Figure 1).
A New History and Geography of Human Genes Informed by Ancient DNA
We have developed methods for using data from modern and ancient DNA to learn about population structure and mixture events. We have used these methods to reconstruct the deep population history of South Asians, Africans, Europeans, and Native Americans. In collaboration with Svante Pääbo's group (Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany), we have used ancient DNA to find evidence for gene flow from Neandertals into the ancestors of non-Africans and from ancient "Denisovans" into the ancestors of Melanesians. In our own laboratory, we have focused on enabling high throughput ancient DNA studies, generating data on hundreds of ancient DNA samples simultaneously to make it possible to understand human population transformations over time.
The Effect of Population Mixture on Human Biology
The finding that many human populations descend from population mixture events is likely to be biologically important. For example, at the time that Neandertals met and mated with modern humans, they were pre-adapted to Eurasian environments, while modern humans were likely not. Thus, modern humans could have used genetic mutations inherited from Neandertals or their archaic cousins the Denisovans to adapt more quickly to the new and challenging environments they were encountering outside of Africa. Indeed, we have now found evidence of places in the genome where increases or decreases in Neandertal or Denisovan DNA are relevant to human biology (Figure 3). We are working to understand the biological impact of archaic mixture on human history, and also to understand how natural selection combined with population mixture. has transformed human populations over the last eight thousand years.
As of April 26, 2016