David Reich

In the Bronze Age, there was an intensification of how people lived with much higher population densities, people living more and more next to their animals and getting their diseases and exchanging their diseases with them and with each other.

And so this is a period of rapid, rapid change in terms of how people are living.

resulting in different biological needs of this population.

So it's not surprising, perhaps, that in the context of these dramatic changes, the biology of the population might be not in the ideally adapted position.

That is that there might be what some people call an evolutionary mismatch, where you take a genetic...

variation that's evolved in hunter-gatherers and put it into farmers or pastoralists, and it's not exactly right.

And so what you're seeing is the DNA of this population, which is descended from hunter-gatherers only 10,000 years ago, reacting to the shock of having been moved into an agricultural and Bronze Age and high population density and urban environment.

And a hypothesis is that what we're seeing is the adaptation that occurs as a result of that.

So we look, one of the things we do in this work is we look carefully at many, many of these positions in the DNA.

We actually have an internet browser that you could look at called the Aegis Browser that Ali and a colleague of his, who's a co-author of our paper, built that allows you to query each of these 10 million positions and see the trajectories at each position and the evidence for selection.

And one of the things that we see is that while for the most part, the signals of natural selection we detect are consistent with being constant natural selection over time, in a handful of them, we're able to see that there's been a reversal or a radical change in natural selection.

And very often that occurs in the period between 5,000 to 2,000 years ago, which is the Bronze Age and the Iron Age, a period of rapid population growth and rapid movement to intensive use of many technologies that were not used that way before.

So an example of this is the TIK2 genetic variant that is a major risk factor for severe tuberculosis, which is the major infectious disease, the most important infectious disease killer in the world today.

And if you look at this major risk factor for tuberculosis, this variant rockets up in frequency from eight or 6,000 years ago to maybe nine or 10% in this part of the world.

And then it rockets down in frequency in the last 3,000 years.

In both cases, there's very clear evidence of natural selection, in the first case to increase in frequency, and then in the next case to decrease in frequency.

And a possible reason for this is maybe the spread of tuberculosis maybe becomes endemic in the population 2,000 or 3,000 years ago.

That's potentially consistent with pathogen sequence data and other lines of evidence.

And maybe this variant was protecting against something before then, but then tuberculosis became significant evidence

after that point, and it was so bad that it pushed in the opposite direction.