David Reich – Why the Bronze Age was an inflection point in human evolution

**Dwarkesh Patel** (0:00)
I am back with David Reich, who is a professor of ancient DNA at Harvard. How do you describe what it is that you study?

**David Reich** (0:09)
I'm a geneticist, and I work on human history and how ancient people relate to each other and people living today.

**Dwarkesh Patel** (0:17)
Great. And so we did an interview, was it two years ago at this point, which ended up being one of the most popular interviews I've ever done. I think people just found really compelling that there's so much human history we don't know and are just learning about now as a result of the kinds of techniques that your lab is using. And you have a new preprint that's very exciting, and I wanted to talk to you about it.
So let's begin. Can you give me a little bit of context on what we're talking about today?

**David Reich** (0:45)
Well, the dream was that when this field started, this ancient DNA field started more than 16 or 17 years ago, that we were going to learn a lot about biology, learn about how people's biology changed over time by getting DNA out of ancient human remains and tracking changes over time. And that dream has really not been realized since the beginning of this field. So while the field's been a big success with regard to learning about human history, it's resulted in surprising findings about human migrations, people not being descended from the people who lived in the same place, hundreds or thousands or tens of thousands of years before, and mixture being common in human history, sex bias processes being common in human history, and things that were not expected from archaeology. And so the field's been a big success from that perspective. But what's not been successful is learning about biology and biological change. And one big reason for that has been that the sample sizes have been too small. So when you have a single person's DNA, it provides a tremendous amount of information about history. And that's because when you look at one person's DNA, it's not a single person, it's many people, it's your two parents, it's your four grandparents, it's your eight great grandparents and 16 great great great grandparents and so on. And going back in time, thousands, tens of thousands, even hundreds of thousands of ancestors going back in time contributing to people today.
So when you look at the DNA of a single person's genome or a Neanderthal genome, you have effectively tens of thousands of ancestors all represented in your data. And you can position that individual exquisitely with respect to other people from whom you have data.
But when you are interested in how a particular genetic variant that affects something like your skin pigmentation or affects your ability to digest cow's milk into adulthood, or affects a behavioral trait, when you want to see how that changes over time, a single person gives you only one sample or maybe two samples, the one that is in their mother and the one that's in their father. And so to get a high resolution picture of how the frequency changes over time, you need to have very big sample sizes of truly very large numbers of people. And we just didn't have that until the last few years. So what motivates this study that we're, I think, talking about today and the work that hopefully another number of groups will be doing in the coming years is the fact that we now finally have those numbers and we can do something with the data to see how frequency changes over time.

**Dwarkesh Patel** (3:13)
Can I ask you a question? I'll be asking a lot of many questions through the next few hours, but why are frequency changes especially interesting?

**David Reich** (3:21)
So what we're interested in is using the experiment of nature that's occurred in our history over the last tens of thousands of years to understand what's biologically significant in our DNA.
If there has been a change in environment that a population has experienced, for example, people have shifted to agriculture or begun living close to domesticated animals or moved to a new environment from a cold place to a warm place or a low place to a high place, then there's pressure on the population to adapt to these new stresses, these new needs. And the way you're going to detect that is you're going to see that the frequency of a genetic variant that, for example, might allow you to live at higher altitude, for example, or that might sort of nudge you to have a different behavioral pattern that might be advantageous in the new situation, that genetic variant might push systematically in some direction in a way that is enough that you can detect it. Now, it's very hard to detect slight shifts in frequency by a few percent or a 10 percent, unless you have a very, very big sample size. And so, what we're looking for are those changes in frequency that are too extreme to be due to chance. And that will tell us that there have been pushes against the biology as a result of the changes in environment that people have experienced.