David Reich
π€ SpeakerAppearances Over Time
Podcast Appearances
And so the approach that we used was we took the DNA samples that we had, most of which were very low percentages of human DNA, less than 10%, often less than 1%, which is such a low proportion that it's prohibitively expensive to sequence them and to just brute force sequencing them, given the technology that we had available at the time.
And so we took these samples and washed them over a artificially synthesized set of short DNA fragments that targeted positions of the DNA that we were interested in analyzing.
So this is more than a million positions that are highly variable in people.
And we picked many of these to be biologically interesting.
We had a whole set of known biological targets that affected traits in genome-wide association studies, which is the way that people look to see if there's particular genetic variants in modern people that have particular impacts and phenotypes and traits.
And so what we did is we had this artificially synthesized set of DNA fragments that we washed our ancient sample over, and it bound the parts of the DNA that we targeted.
And the resulting sequence that we generated was very enriched for the parts of the genome that were informative about history.
And even though only 10% or 1% of the DNA was human, it ended up that a very large fraction was from the parts of the genome that we were interested in, and it became economically efficient to do it,
It's mostly microbial.
So it's from bacteria and fungi that colonize a person's body after they die.
Depending on how they die, there'll be more or less of these bacteria and fungi.
And so when you typically sequence DNA from a person, it'll just be full of microbial sequence.
Sometimes the microbial sequence is very interesting.
So it might be pathogens that a person died of.
So there's, for example,
amazing work about, for example, different plagues of malaria and black death and hepatitis B and so on that have been obtained from the sequences of these pathogens in people's teeth and other parts of their body when they died.
But we're focusing here on the human DNA.
And so what we did is we, this changed the amount of data that was possible to produce from tens per year to hundreds per year.
And then we further roboticized and industrialized the process so that there were many hundreds or even thousands per year.
And so just in our laboratory, we've been generating genome scale data from more than 5,000 individuals per year.