Origin: A Genetic History of the Americas

often impossible to complete the genomic jigsaw puzzle. Either there
simply aren’t enough molecules preserved, or the ancient human’s DNA is
so scarce compared to all the other DNA in the extraction (from soil
microbes and other sources) that it would be prohibitively expensive to
sequence to levels high enough to get all the pieces needed to assemble for
a whole genome. Imagine trying to put together an extremely hard 1,000-
piece jigsaw puzzle when its pieces are mixed into a pile with 100,000 other
pieces from 100 other puzzles, and every piece that you pull out of the pile
costs you money. This is a pretty accurate description of what it’s like to try
to sequence a nuclear genome—often 1% or fewer of the total DNA
fragments you get out of an extraction will belong to the ancient human.
You can screen DNA extractions to estimate how much human DNA is
present and whether there’s enough to make sequencing worthwhile.
Screening saves you a lot of money, but the downside is that it means you
can only get genomes from a tiny number of individuals with exceptional
preservation.
A second approach is to fish for the human DNA out of the pond of all
DNA fragments in the extraction, a process called target capture. To do this,
you use baits—fragments of human DNA or RNA that bind to their
corresponding DNA sequences, which have been preselected by researchers
as informative for population differences. These baits are created from a
modern human genome, and they are engineered to be attached to biotin
(also known as vitamin H), a molecule that likes to attach to a protein
known as streptavidin. The biotin-streptavidin binding is so strong that it’s
used for countless clever applications in molecular biology. In the case of
this ancient DNA fishing expedition, researchers coat magnetic beads with
streptavidin. When they have baited the pond of DNA fragments, they mix
them with the beads. The baits bind to the streptavidin-coated beads, which
are then held in place by magnets as they are repeatedly washed. All
nonhuman DNA is thus removed, and (after unhooking the DNA “fish”
from the baits) the purified ancient human DNA fragments can then be
amplified and sequenced. This approach provides data from preselected
sites across the whole nuclear genome while being vastly cheaper and more
feasible than trying to sequence the whole genome outright. A group of
scientists has made the sequence for their capture probes for over 1.2
million spots across the genome (the 1240K capture array) freely available