Today’s guest is Dr Pontus Skoglund, an evolutionary geneticist at the Francis Crick Institute! Pontus is the group leader of the Ancient Genomics Laboratory , which applies and develops ancient genomics to understand past human diversity, primarily focusing on major evolutionary events and their impact on human societies and health. Originally from Sweden, he obtained his PhD from Uppsala University in 2013, and thereafter did his postdoctoral research in David Reich’s laboratory at Harvard Medical School’s Department of Genetics. His research covers a range of topics within evolutionary genetics, such as the link between population migrations and the global transition to agriculture, archaic gene flow, early human evolution in Africa, the peopling of the Americas, and the origin of domestic dogs.
What are your research interests and your particular area of expertise?
I work on ancient genomics, specializing in making sense of ancient DNA data, and the issues that come with it, to learn about genomic history, adaptation, and the human past.
What originally drew you towards evolutionary genetics?
As a kid, I probably visited the Swedish Museum of Natural history in Stockholm over 20 times, but I can’t say that I always knew what I wanted to do. I was always interested in evolution because it relates to who us humans are, but also has a few almost-mechanistic forces (for example mutation) that makes it reminiscent of another topic I really liked in school: physics. So I was very drawn to evolutionary genetics but also conflicted about its historical legacy, which includes eugenics. There was a vibe of biological determinism associated with genetics that was uncomfortable, but it seemed genuinely interesting how we can understand ourselves as the product of both evolution/biology and our social surroundings. Today I think that the more people that enter fields with historical legacies like that, the better. Evolutionary genetics is very exciting in that it crosses perspectives: the past and the future, paleoanthropology and biomedicine.
What was your PhD topic? Where did you complete your PhD and who was your supervisor?
I started my PhD with Mattias Jakobsson at Uppsala University in 2009, and finished in 2013. I had done an MSc project on ancient DNA with Anders Götherström before that and was very attracted to the temporal data that ancient DNA promised. In 2009, ancient DNA was almost laughed at, and seen as a niche pursuit among human geneticists. But for those who looked beyond that there was already evidence that genomic sequencing was possible in principle. In any case, I thought that it would be more important to learn to work with large-scale genomic data for that eventual future, and thought it could be a great opportunity to work with Mattias, and it was. When I started, I didn’t really have a project, just to study human genomes, probably from the present-day, to understand history.
What were the findings from your PhD?
What ended up being the central project was that my thesis co-advisor Anders Götherström and his group had for long been interested in the question of whether farming practice spread through Europe by migrating human groups or as a viral idea, ’memes or genes’. In Scandinavia, people practicing farming and foraging coexisted close together around 5,000 years ago. At the time, there were no ancient human genomes and it seemed that ancient genomes were for huge projects like the Saqqaq genome and the Neandertal genome, both published later in 2010. How could we use this clearly amazing thing that was next-generation sequencing of ancient DNA to do ‘proper’ human statistical genetics, not just of mitochondrial DNA? It seemed nearly impossible to deal with the contamination issue, there was just no way to know nuclear DNA was real unless a high-quality genome could be obtained, or the genome was of a rare ancestry that could not be from contaminating people. Nevertheless, I suggested trying out the direct sequencing approach that we had worked on during my MSc thesis on Anders’ material, as a direct test of whether the two cultural groups reflected different populations.
Sequencing complete genomes would cost a fortune, since the DNA is so poorly preserved, but maybe even just about 1% of random sequences scattered across the genome of each individual could be enough. Since we didn’t have to directly compare each ancient individual to the others, we could use the medical databases of living people’s genomes to connect the dots, and Mattias was an expert in that type of data. The results were quite astonishing to us, prehistoric hunter-gatherers in Scandinavia did not match the genetic makeup of any populations in Europe today, but they were most similar to people in the northern parts of Europe. Farming-associated individuals shared close ancestry with present-day people in the Mediterranean. The data thus suggested Neolithic groups spread across the European continent without much influence from the local people. What I was most excited about was a solution to the contamination problem: I isolated the sequences that showed clear signs of ancient DNA degradation computationally and showed that the results were the same, which was a new approach that is now common. Then, I ended up spending the rest of my PhD working on improving these methods for dealing with modern contamination, and using the analysis approaches on collaborative projects with others, on questions ranging from present-day variation in southern Africa with Mattias and Carina Schlebusch, to remove contamination from a Neandertal sequenced by Johannes Krause and Svante Pääbo, and to help on Eske Willerslev’s projects on genomes from the Americas, which were all very exciting too.
After your PhD, where have you worked? Where has been your favourite place to work?
After my PhD I worked as a postdoc in David Reich’s lab at Harvard University which was a wonderful and highly rewarding experience, and then I moved to my current work at the Francis Crick Institute. As a place and building, my favourite would be the Crick, it is very inspiring and a great place to be a part of the UK archaeo-scientific community.
What current projects are you working on at the Francis Crick Institute? Where do you hope these go in the future?
One of our main interests is to study the past few thousand years of a region in some detail with full genomes: Britain. The reason is not only the detailed archaeological record and community here, but also that the #1 resource in medical genetics is the UK biobank of half a million people. We are hoping to understand genomic history in detail, but also bring ancient genomics and medical genetics together by learning about the evolution of diseases and traits over all the complexities of history. We are also interested in working on the frontier to obtain ancient genome and proteome information from times and places where it is very hard to get it to understand deeper human evolution.
As a geneticist, do you approach questions about the past differently to an archaeologist or anthropologist?
I think most similarly to paleoanthropologists, as we are often studying patterns that occur on the time scale of population history, hundreds or thousands of years. I have been in constant interaction with archaeologists and anthropologists since the beginning of my PhD. It is always very exciting, and face-to-face it is always pleasant to talk with the most genetics-sceptical of archaeologists. A lot of the perceived differences are communicative, but there are also differences in perspectives. To many, and to me as I considered starting in the field, genetics also has a vibe of the old politically-driven race sciences. It is our responsibility to overcome it. A person who was an early role model for me in this was Carina Schlebusch in Uppsala, in how she approached genetic studies of the past in southern Africa.
Is ancestry the most important thing to understand about the human past? Probably not, but all archaeologists and anthropologists I know agree that it would be an amazing information resource to know the parents of everyone who ever lived, the grand weave of human ancestry. Ancient DNA is the closest we can get to that.
Do you work on other projects outside of human evolution studies?
I have been interested in the origin of dogs for a long time, since I was an MSc student. When and where it happened is unknown, to me it is one of the major remaining ‘known mysteries’ of the Upper Paleolithic that should be possible to solve with ancient DNA. We have an ongoing project in the lab on ancient dog and wolf genomes and are hoping to understand the original domestication process, how wolves and dogs evolved over the past 100,000 years, and how tracking dog DNA can teach us new things about human history.
What advice would you give to a student interested in your field of research?
Setbacks and rejections are inevitable, and though it may seem so, almost no one is born with a thick skin. As Paul Nurse, our director here at the Crick, says, most hypotheses are wrong so research is about failing again and again, and university doesn’t really prepare you for that. I would also say that reading the best papers in your field is like cardio to a researcher, and the best way to lead you into developing the right technical skills and identifying interesting questions. Be sincere in your research, be proud of the scientific ethos of finding the truth. Finally I would invest some time in quantitative and computational skills, useful in any discipline related to human evolution.
What do you think has been the most revolutionary discovery in your field over the last 5 years?
For the readers here who may be most interested in deeper human evolution, I would say the finding of particular individuals such as the Oase 1 individual from Romania that has a very recent Neanderthal ancestor, and the archaic human person from Denisova cave that has both a Neanderthal and a Denisovan parent. Until these individual finds, admixture between evolutionarily distant human populations has been somewhat of a statistical abstraction, with many unknowns. While these finds confirmed processes that were in principle already known by statistical analyses of other genomes, I think they provide stable data points that are rare in a field where it can be difficult for many to distinguish between reliable and exaggerated statistical claims.
If you were not an evolutionary geneticist, what would you be?
Within research I would have a hard time picking another topic. I would have enjoyed studying computer science more closely, and perhaps worked on something more directly oriented towards the human future rather than the past.