It is my absolute pleasure to introduce today’s guest, Professor Lluis Quintana-Murci, a population geneticist at the Pasteur Institute and Collège de France! He has led the Human Evolutionary Genetics Unit at the Pasteur Institute since 2007, and also currently holds the position of Professor of Human Genomics and Evolution at the Collège de France in Paris. Lluis is internationally renowned for his research on the genetic architecture of human populations and the role of genetic diversity in human adaptation. His team are particularly interested in how genomic data can be used to infer the past demographic history of our species, to explore how natural selection influences human diversity and to understand how pathogens have shaped human evolution.
What are your research interests and your particular area of expertise?
My area of expertise is human population genetics, with an emphasis on understanding both the demographic past of human populations and the various ways through which they have adapted to local environments – climatic, nutritional or pathogenic – all along their journey around the world. I am particularly interested in two areas of the world: Central Africa, which hosts the largest group of living hunter-gatherers (the so-called rainforest hunter-gatherers or ‘pygmies’) and, more recently, the Pacific.
I also have a strong interest in how pathogens and infectious diseases have shaped human evolution, since infectious agents have accompanied humans since their emergence in Africa. Understanding how natural selection imposed by pathogens has affected the diversity of our genomes is an alternative way to identify genes and biological functions that have play a key role in human survival against deadly infectious diseases, which highlights the value of dissecting the most natural experiment ever done: that of Nature.
In the context of selection and adaptation, I have a strong interest in how admixture, be it ancient or modern, has influenced human adaptation. In other words, when one faces a new environment to which they need to adapt, instead of waiting for an advantageous mutation to appear and increase in frequency in the population, why not rather admix with another population that already harbours the advantageous mutation in their gene pool? We have been quite focused on this topic over the last few years, in particular, on how ancient early Europeans acquired, though admixture with Neanderthals, advantageous variants involved in resistance to infectious diseases.
What originally drew you towards evolutionary genetics?
A combination of many things. I grew up in Mallorca, an island of the Mediterranean, so my contact with nature was quite important. I liked the sea a lot and my mother used to show me documentaries about Jacques Cousteau and his sea explorations (that was the only way I shut up immediately…since I was a very, very chatty child). These things conditioned me to like nature and I wanted to be a marine biologist. At the same time, ever since I was a child, I have always been very attracted by other cultures and people speaking other languages. I remember listening carefully on the beach to the languages spoken by tourists. I did love that, it was my own way of traveling. I’ve felt attracted to human diversity since ever. All this, together with my strong interest in history and story-telling, naturally brought me to population and evolutionary genetics, where diversity, history and stories form the basis of it.
What was your PhD topic? Where did you complete your PhD and who was your supervisor?
I did my PhD in the University of Pavia (Italy) under the direction of Silvana Santachiara-Benerecetti, one of the first students of Luca Cavalli-Sforza. Indeed, during the early 90’s where I was doing my PhD, Cavalli-Sforza spent a few months in the departments, swinging between Pavia and Stanford. It was a great place to do a PhD in population genetics, given the strong evolutionary and population genetics flavour of the whole department. Life-wise, it was less fun…having lived in Mallorca and Barcelona in the ‘post-movida’ 80’s period, living in a small provincial Italian city was like travelling back to the 50’s during my grandmother’s childhood! The topic of my PhD was the evolutionary history of eastern African populations through the study of mitochondrial DNA and Y chromosome markers, which was the best you could do in population genetics in the early 90’s.
What were the findings from your PhD?
They were super cool. We first found a mitochondrial DNA marker of Indian origin in various Ethiopian populations, and we wondered whether it was the result of recent admixture or if it was an old lineage present in eastern Africa that was brought to India. By enlarging our sample sizes from eastern Africa and several Asian and European populations, we showed that indeed we had discovered an old marker that supported a coastal route out of Africa of modern humans 60,000 years ago, starting from the horn of Africa and following the coasts of south Asia. This was the first genetic evidence of a coastal route of exit of modern humans out of Africa, and was published in Nature Genetics in 1999.
After your PhD, where have you worked? Where has been your favourite place to work?
After my PhD, I have been essentially living in Paris all the time. In theory, I came here 20 years ago for a post-doc and I never left! Work-wise the Pasteur Institute is great, and Paris….is Paris! I immediately felt in love with this city. It is a good balance between a southern city and a northern city. Though don’t think that I am chauvinist, since I am not French! (well, I guess I am also French now). But seriously, I really like Paris both to work and to live. Having said that, I have spent periods in other cities as an invited researcher or professor. I have great memories of Tucson (Arizona) where I spent some months in Mike Hammer’s lab. I loved that city, a bit calm for my taste, but the nature was amazing. I also spent a summer at Rockefeller University two years ago…one of the best experiences of my life. I do love NYC!
What current projects are you working on at the Pasteur Institute Where do you hope these go in the future?
We continue to work on the demographic and adaptive history of humans, but with a stronger focus now on the South Pacific. This region of the world is a land of contrasts, as it was first peopled just after the out-of-Africa exodus, around 45,000 years ago, then no immigration occurred until around 4,000 years ago when Austronesian-speaking peoples, most likely from Taiwan, entered the region. It is also super interesting that some populations from the Pacific present the highest worldwide levels of combined Neanderthal and Denisovan ancestry. We are dissecting the demographic past of this region and exploring how the ‘archaic’ ancestry found in these populations participated in their adaptation to the island environments of the Pacific.
On the other hand, we maintain a strong interest in immunity and infectious diseases. In particular, we are exploring the genetic, epigenetic and environmental factors that drive our differences in immune responses. We are all different, we are all diverse (fortunately!), and we want to understand the sources of such diversity. We are also studying how ethnic background, age, sex and metabolism influence our susceptibility to infection, using as a model influenza A virus and…SARS-CoV-2!
What advice would you give to a student interested in your field of research?
Just one. Be passionate. If you like science, all will come along perfectly. Because if you like science, you will naturally work hard on it. Some people really insist that we should maintain a good work-life balance. And this is very true. But sometimes I don’t really understand it, as I do many things in my life, science, writing, reading, gardening, watching movies, eating, etc…but when I do science, I don’t think “Now, time to work”. For me, science is totally integrated into my “life”. Hopefully that makes sense…. I guess what I mean is that the only healthy advice I can give is: if you like science, go for it, you will find a job and you will enjoy it. A bit of mobility also helps to find a job.
What do you think has been the most revolutionary discovery in evolutionary genetics over the last 5 years?
I am obviously biased but, for me, it has been the discovery, bolstered by the progress in paleogenomics, that admixture with ancient hominins like Neanderthals or Denisovans helped early modern humans to adapt to their local environments, a phenomenon known as ‘adaptive introgression’. As some of my colleagues say, ‘this part of Neanderthal that is within us’ helped early Eurasians to adapt to cold climates and pathogens, viruses in particular, among other phenotypes.
If you were not an evolutionary geneticist, what would you be?
That’s tricky. So many things. If I had to remain in science, I would be a marine biologist, my first passion, and work on the behavioural biology of Cetaceans. I am fascinated by the complexity of their social relationships as well as by their mode of communication. Outside of science, I would have liked to be a writer, which actually I do a lot in science anyway, and it is also something that I love. I like the mixed feeling of suffering and satisfaction that comes at the same time when writing. Yes, I would have liked to be a writer.
Conversations in Human Evolution 