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Origin: A Genetic History of the Americas

by Jennifer Raff

by Jennifer Raff

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looking good.<br />

Amplification and sequencing <strong>of</strong> mitochondrial fragments is a bit <strong>of</strong> an oldschool<br />

way <strong>of</strong> studying ancient DNA. As I mentioned before, although<br />

mitochondrial DNA can tell us a lot about a population, it does have some<br />

limitations. When methods for reading <strong>the</strong> DNA sequences <strong>of</strong> complete<br />

nuclear genomes—all 3 billion base pairs—became available, <strong>the</strong> ancient<br />

DNA community quickly realized <strong>the</strong>ir potential. It took time to optimize<br />

<strong>the</strong> DNA extraction methods for <strong>the</strong>se approaches. Talented researchers<br />

identified <strong>the</strong> skeletal elements that were likeliest to contain enough DNA<br />

preserved for whole genome sequencing, which turned out to be teeth and a<br />

small pyramid-shaped section <strong>of</strong> bone at <strong>the</strong> bottom <strong>of</strong> <strong>the</strong> skull that<br />

contains <strong>the</strong> inner ear bones (called <strong>the</strong> petrous or rocklike portion, in<br />

recognition <strong>of</strong> its density). O<strong>the</strong>r researchers perfected <strong>the</strong> extraction<br />

method that I used, allowing <strong>the</strong> smallest DNA fragments to be captured<br />

and cleaned.<br />

Having ascertained that <strong>the</strong>re was ancient mitochondrial DNA preserved<br />

in <strong>the</strong> tiny drops <strong>of</strong> liquid at <strong>the</strong> bottom <strong>of</strong> my tube, I was back in <strong>the</strong> lab a<br />

few weeks later to make a genomic library. Sitting at <strong>the</strong> benchtop inside<br />

<strong>the</strong> highest-pressure room, I slipped my arms into <strong>the</strong> hood and began to<br />

carefully mix a small amount <strong>of</strong> my DNA extraction with water. Keeping<br />

all <strong>the</strong> tubes inside a chilled rack to prevent <strong>the</strong> reaction from starting<br />

before I was ready, I added a few drops <strong>of</strong> a buffer and a tiny amount <strong>of</strong> a<br />

powerful (and outrageously expensive) solution and pipetted <strong>the</strong> solution a<br />

few times to make sure it was completely mixed. I <strong>the</strong>n placed <strong>the</strong> tube<br />

inside <strong>the</strong> <strong>the</strong>rmocycler we keep inside <strong>the</strong> ancient lab and pressed a few<br />

buttons. After returning <strong>the</strong> reagents to <strong>the</strong> freezer, I settled back in my<br />

chair to wait.<br />

For <strong>the</strong> next 45 minutes or so, as I was absorbed in a podcast, <strong>the</strong><br />

machine slowly warmed <strong>the</strong> solution, first to room temperature and <strong>the</strong>n to<br />

a blisteringly hot 145°F (63°C). Inside <strong>the</strong> tube many millions <strong>of</strong> random<br />

DNA fragments that had been extracted from <strong>the</strong> sample were having <strong>the</strong>ir<br />

ends “repaired.” i Think <strong>of</strong> each tubeful <strong>of</strong> DNA as containing millions <strong>of</strong><br />

tiny little snippets <strong>of</strong> ribbons that you want to use for an art project, but <strong>the</strong>y<br />

have been chewed up by a rodent. Looking at <strong>the</strong> ribbons under a powerful

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