- I'm very pleased to welcome you to this public talk sponsored by the Department of Biochemistry, the great Department of Biochemistry. And we're thrilled to have Svante Paabo here with us this afternoon. This talk is part of the Biochemistry Colloquium's International Steenbock Lectureship, and that's funded by the estate of Harry Steenbock. Svante Paabo is a world-renowned researcher from the Max Planck Institute for Evolutionary Anthropology in Germany. He's a founder of the field of paleogenetics, the study of ancient DNA. He uses DNA obtained from ancient bones to piece together human origins and the history of how we spread across the globe. He has shown how much DNA we share with Neanderthals, and how some genetic variance from the Neandertals are beneficial, while some are involved in disease. And my colleague Aseem Ansari, Professor of Biochemistry, will tell you more about Svante's work and introduce him, thank you.  - Thank you, Marsha. This is the first International Steenbock Symposium Lecture series and it has been an unusual one because this is the first time we've actually had a second lecture in the Historical Society. So that tells you of the broad appeal of the deep and abiding question, the mystery that Professor Paabo is investigating. That is, of our origins, of our human origins. Where did we start? What other types of archaic humans might have been? And where are we today? How do they contribute to our being here? He started this, I first noticed his papers from 1987, where he was among the first people to clone a mummified DNA from Egyptian mummies. And from then onwards it has been just an intellectually stimulating series of contributions, both scientific and making it accessible to general audiences. That's what you're seeing today. You can see much of that work in over 290 papers that he's published, most of them in some of the world's best journals, but even more interesting I recently discovered I had not seen this before but I recently discovered his book The Neanderthal Man. This tells you about his personal journey as he traveled through those 30 years, making his way, in the last few years deciphering the Neanderthal genome, incredible resolution, you hear about it today. As well as Denisovan genome and other archaic that he's pursuing. With that I would also like to say, those 30 years, the advancements that he's made, both scientific and conceptual, have brought him numerous awards. Yesterday when I tried to introduce him, I sort of mixed things up because they were just so many. So today I decided not to try and list all the awards that he's won, except to say that he's won some of the most prestigious awards and is a member of some of the most prestigious societies and national academies. Most people work a lifetime to be a member of one national academy. He's a member of a dozen, including the US National Academy of Sciences, German, Swedish, Finnish, Russian. Uncommon to have that. He has been widely recognized for his amazing and penetrating work. I would also like to point out that he has had a direct impact on UW, he's contributed to UW in many ways. First of all, bringing the science and the humanities communities here together. General audience. This is one very clear evidence of his impact on our community. The second one is Jesse Dabney and his mentor Bill Aylward, who's studying Troy. Where is Jesse, Jesse, stand up. There he is, stand up, stand up. Jesse is Paabo's student. He did his PhD work at the Institute, the Max Planck, that Marsha just mentioned. And he is now here with William Aylward, trying to essentially build the Molecular Archaeology Group. This is an attempt to bring together chemists, genomicists, biomathematicians, anthropologists, archaeologists, et cetera. So already you can see Svante's immediate impact on our community. We look forward to all sorts of wonderful things that this Molecular Archaeology Group will do for us with Jesse and William at its helm. With that, let me invite Professor Paabo to tell us about the amazing stuff that he's done over the last several years.  - Thank you very, very much for the very generous introduction. I'm both pleased and honored to be here for this first Steenbock symposium. I have had two wonderful days on campus talking to many, many people and learning many things. So what I then wanted to do is to talk to you a bit about how we have been able to reconstruct the genome of Neanderthals, relatives of Neanderthals, what we learned from that, talk a little bit about what we begin to learn from studying the genomes of very early modern humans outside Africa and in the end talk a bit about functional implications of this. Functional implications of the contribution from Neanderthals and Denisovans their relatives to present-day humans. And what we can learn maybe about what's specific to humans relative to Neanderthals. Let me start out by pointing out what you already know, I think, that our genetic materials, DNA stored on chromosomes in all cells in our body so we can study our genome looking at DNA from such chromosomes from any cells. And this DNA molecule, as you know, let's see if I, I do have a pointer here this DNA molecule is double-stranded, as you know. The information is encoded in a sequence of four letters or nucleotides. And the two strands are really important because when a cell divides there are enzymes in the cell that take these strands apart and you synthesize. New strands with the old as a template in a very exact process but there are then errors that are sometimes made. Sometimes a wrong base is built in. You have a mutation. And if this happens in the germline and it's not repaired before the next separation comes, it will appear in the next generation as a mutation that you can detect in the form of a difference between two human DNA sequences that you compare. If you compare two genomes of people in this room, you have a difference about every 1200, 1300 letters, there's a difference between two genomes. And these mutations rain down on our genomes approximately as a function of time. So if we add in here a chimpanzee, you will have more differences. You will have about a difference every 100 bases or so. If you're now interested in the history of our genomes or the history of a DNA sequence, what you will do is study these differences, use the best models that we have for how these mutations accumulate, and reconstruct the history, and depict it in the form of a tree like this. Very simple in this case. The two human sequences go back to common ancestors recently, much further back once shared with the chimpanzees. And you know also that we have three billion bases in our genome. So a difference every thousand or so means there are three million differences between any two genomes, also between the two genomes inherited from your father and your mother, so there's a lot of information to reconstruct history here. If you now do that and look on this variation world-wide, what you will find is that you find most variation in Africa. And you take the entire world outside Africa, although there are a lot more people living outside Africa than inside Africa, because you have less variation there. And in addition, most of the DNA sequences you find outside have close relatives inside Africa. But there is a component, if you like, of the variation inside Africa that have no close relatives outside. So the interpretation of this pattern is then that modern humans, that is the direct ancestors of people living today, evolved in Africa, accumulated variation there, and a part of that variation went out and colonized the rest of the world. You can also estimate approximately when that happened. And it's rather recently in sort of evolutionary terms within the last hundred thousand years or so. When these modern humans then came out of Africa they must have met other forms of humans that existed since a long time in Eurasia. Neandertals to western Eurasia, other forms farther east in Asia. And we are then, our lab, is sort of, if you like, sort of obsessed with these Neanderthals. You may then ask, well, first of all remind you about th