► Laboratory on Molecular Paleontology of IVPP
The main purpose of our ancient DNA laboratory is to research topics in evolutionary and population genetics, using molecular genetic approaches to clarify ancient human relationships, archaic hominid introgression into modern humans, migratory routes of early modern humans into Asia and interactions between early modern humans and contemporary local modern humans. Moreover, we use ancient genetic data to investigate the impact of Neolithic agriculture on demographic changes across Europe and Asia and look for potential local adaptations leading up to modern human populations. Major areas of research include:
1. Archaic introgression into early modern humans
In the last few years, the sequencing of multiple archaic hominids has shown that archaic introgression contributed significantly to many human populations globally. An affiliation between the Denisova genome from the Altai Mountains to Melanesians in the Pacific (Meyer et al., 2012, Reich et al., 2010) suggest a more complicated story in East Eurasia than is currently explicable using only present day East Eurasian genomes. Higher levels of Neanderthal ancestry in East Asians (Wall et al., 2013) also begs the question of what is missing in our understanding of East Asian prehistory. More recent work on ancient Eurasians (Fu et al., 2016, Fu et al., 2015, Haak et al., 2015, Lazaridis et al., 2014, Fu et al., 2014) suggest admixture from basal non-Africans into Europeans, lending support to a more complicated Eurasian history than was imagined before the use of ancient data. Evidence also exists that some genes under positive selection in East Eurasians may have originated in archaic hominins, crossing over to human populations with introgression (Huerta-Sanchez et al., 2014, Williams et al., 2014, Abi-Rached et al., 2011). We will sequence and analyze ancient East Eurasians from the last few tens of thousands of years, to determine the role archaic introgression played within East Eurasia.
2. Demographic history in East Asia
It is not well understood how past dynamics led up to the present day composition of East Asian populations. With only one partially sequenced ancient genome from East Asia (Fu et al., 2013)and low genomic diversity in present day populations, the paths and timing of migration into East Asia are murky. By including ancient genomic data from East Asia, we will supplement present day data with sequences representing past populations, which will help to clarify modes of migration and population structure and transition in East Eurasia in the near past.
3. Genetic adaptation in East Eurasia
Several genes are believed to have undergone positive selection in East Eurasia, including EDAR, associated with thicker hair, more active eccrine glands, and altered tooth shape in East Asia (Kamberov et al., 2013), EPAS1, related to adaptation to life at high altitudes on the Tibetan Plateau (Huerta-Sanchez et al., 2014, Yi et al., 2010), LCT, which may be tied to independent adaptation to lactase persistence in Tibet (Peng et al., 2012), and SLC16A11, which affects skin pigmentation (Williams et al., 2014). In studying ancient East Eurasian samples, we will determine in which ancient East Eurasian regions the adaptive variants first appeared, as well as the rate and degree of spread prior to the present day. Furthermore, a genome wide scan including ancient East Eurasian genomes may reveal more genomic regions that have undergone positive selection in the past. East Eurasia is believed to have undergone an independent development of agricultural practices relative to West Eurasia. This suggests unique adaptations in East Eurasia that would not be found in studying only West Eurasians. Understanding how different functional genes were affected by selection in East Eurasian populations provides insight on the dynamics in present day East Eurasian populations. Understanding adaptive pressures in a population's history can inform greatly on appropriate procedures for medical treatment and understanding risk factors within present day populations.
4. Host-Pathogen Coevolution in East Eurasia
Many pathogens are believed to have a long history with human populations, and have coevolved with them over the last few tens of thousands of years. In particular, two such pathogens are Mycobacterium leprosae and Mycobacterium tuberculosis, two mycobacterial species that have been found in many ancient skeletons and are found in a large fraction of present day populations. When humans are infected and diagnosed with leprosy or tuberculosis, respectively, the potential effects can be devastating, oftentimes fatal. Previous research (Bos et al., 2014, Schuenemann et al., 2013, Taylor et al., 2013) has shown how ancient genomes of these two pathogens have provided new insights on their evolution from the last few thousand years to the present day. However, these studies have been focused on West Eurasia and the Americas, and give little insight into major questions on East Eurasian strains raised by studies on modern genomic data (Luo et al., 2015, Comas et al., 2013, Monot et al., 2009). For both pathogens, migration to East Eurasia and from East Eurasia into the Americas is not well understood. The most virulent and prevalent strain of M. tuberculosis, known as the ‘modern Beijing' strain, comes from China but is not representative of the wide diversity of other M. tuberculosis strains found in East Asia, lending urgency to understanding the prehistoric context in East Asia within which this strain arose and spread. Our lab will sequence these bacterial genomes from sites across East Eurasia throughout the last few thousand years to better understand how these pathogens spread and persisted in East Eurasia, and how they relate to present day East Eurasian strains.
Our group is not only highly proficient in using the key technologies required for sequencing ancient DNA, we have also conducted large genome-wide projects and published breakthrough articles, thereby demonstrating keen research perspectives, rigorous scientific practices and strong analytical capabilities in addressing problems in population and evolutionary genetics as well as molecular biology. Our contributions include: the estimation of the proportion and time of gene flow between Neanderthals and Late Pleistocene Central Asian and Siberian humans, using high-quality early modern human genomes; and the discovery that contemporary European populations are comprised of at least three different sources of genetic ancestry, revealing that modern human migration was not straightforward. These are some of the accumulating knowledge and experience within this lab, laying a solid foundation for future research.
Our laboratory has enduring relationships with many international teams at the forefront of ancient DNA research. Most notably, are the continual collaborations with the German Max Planck Institute of Evolutionary Anthropology Professor Svante Pääbo's team. Professor Svante Pääbo is one of the founding members in the field of ancient DNA research, and has had impressive results in leading his team to solve fundamental questions about human origin and evolution, and participating teams are also using advanced experimental and bioinformatics methods leading by international standards. In addition, our laboratory maintains in-depth exchanges and cooperation with the Department of Genetics at Harvard Medical School, in terms of joint research on human origins.