Journal Club

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Journal Club: High-throughput sequencing transforms the study of human evolution

In the last five years, great strides have been made in the field of human evolution, such as the sequencing of the Neanderthal genome that revealed that modern humans and Neanderthals interbred, and the discovery of an extinct branch of humanity known as the Denisovans. These advances were made using high-throughput sequencing that could sequence ancient human DNA at rates previously thought to be impossible. This approach promises to soon yield even more insights on human origins, and one day maybe even the genome of the species that gave rise to Homo sapiens, according to a review appearing in the February issue of the Journal of Human Evolution.

The ancient human DNA that survives in fossils typically has degraded into short fragments, and usually comprises no more than 5 percent of the DNA in ancient samples; the rest consists of contaminants. Previously, scientists relied on PCR (polymerase chain reaction) to detect ancient human DNA fragments in amongst overwhelming pools of contamination in order to generate copies of these snippets for sequencing. But PCR is an impractical and expensive approach — sequencing a Neanderthal genome just once using PCR would have required about 20 grams of bone and 6,000 runs, a prohibitively costly exercise, evolutionary geneticist Hendrik Poinar at McMaster University in Hamilton, Canada, and his colleagues noted in the article.

Now scientists use high-throughput sequencing technology to sequence millions of ancient human DNA molecules in parallel, a strategy that both generates far more data and reduces the price of sequencing. Currently, the cost is roughly $0.07 to $10.00 per million bases sequenced, depending on which platform and sequencer researchers use, the reviewers noted.

One discovery that high-throughput sequencing led to was that 1 to 4 percent of the modern human genome is Neanderthal in origin, revealing that our lineages admixed. “We’ve sequenced the Neanderthal and Denisovan genomes, and many more full human genomes are on the way,” Poinar said. “Admixture seen between these groups will reduce the image of isolated populations and show a lot more interconnectedness in the past.”

Paleogeneticist Carles Lalueza-Fox at the Institute of Evolutionary Biology at Barcelona, Spain, who did not take part in this review, said the most exciting aspect of next-generation sequencing technologies is moving paleogenetics to the population level, “especially in more recent periods where we have literally thousands of samples.”

“In the case of the European prehistory and recent history, one of the fields that I think will burst in the next few years, we will be able to test archaeological and anthropological hypothesis about different past migrations and cultural horizons that sometimes have been debated for many decades,” Lalueza-Fox added. “Eventually, we will solve these archaeological controversies, because we will have genomic data from real people that lived, moved, adapted, migrated and died in those periods.”

The future of ancient human DNA studies may delve into  even more distant times. So far, high-throughput sequencing has managed to analyze 400,000-year-old DNA from an unknown hominin that shared a common ancestor with Denisovans. But Poinar and his colleagues suggest it could even help explore DNA from Homo erectus, which lived 143,000 to 1.8 million years ago, and Homo heidelbergensis, which lived 200,000 to 700,000 years ago.

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