Origin: A Genetic History of the Americas

(9).
My libraries were finished. Over the next few days, I verified that the
library preparation was successful. Initial sequencing of a small number of
the reads from the library showed that the ancient human DNA molecules
made up about 10% of the total DNA in the sample, enough to let me
sequence the entire genome. As soon as I received the data files from the
sequencing run, I gratefully passed them along to a collaborator who
specializes in analysis of ancient genomes and tried not to be too impatient
as I waited for the results of an analysis of, the first genome to ever be
sequenced from this region of the Americas. I worried about many things:
that the DNA wouldn’t produce a high-quality genome, that one of the
larger labs would scoop me (publish a result from this area before me), that
I would misinterpret the results, and what the descendant community would
think of them. But worrying about things that I could not control got me
nowhere, so I tried to push the project from my mind for a few weeks and
let my collaborator work in peace.
When the first ancient genomes began to be sequenced, computer
programs had to be developed to distinguish between genuine ancient DNA
fragments, those of modern contaminants, and the genomes of
microorganisms that are co-extracted from any sample. One major
breakthrough was the realization that ancient DNA has characteristic
damage patterns that distinguish it from contaminating modern DNA. ii That
meant that by using a particular kind of program, one could estimate the
degree of modern DNA contamination and distinguish between damaged
and undamaged reads.
Additional methods were developed to match tiny ancient DNA
fragments to a map of the complete human genome reference sequence.
This allowed the book of a person’s genome to be assembled from the
millions of random sentence fragments that we recovered from their bones.
The greater the depth of sequencing—the more times we had a word or
sentence confirmed by multiple fragments—the more confident we could be
in distinguishing between the true DNA sequence and damage.
Computational geneticists invented new ways of comparing ancient
genomes with other genomes from ancient and contemporary people and
developed powerful tools for modeling population histories using these new
kinds of data. Now we could estimate changes in population size at