We've reported in the past that researchers were attempting to sequence the Neanderthal genome in an attempt to better understand the origin of modern humans. The need for this project might have gotten a boost from a recent report that suggested that at least some of this pre-modern human lineage lives on in our own genomes. So it seems to be a perfect time to provide an update on how that work's going. Conveniently, both Nature and Science have obliged, and they describe different approaches to this attempt to understand our ancestry.
The Nature paper provides an excellent summary of the difficulties posed by the problem of getting an accurate sequence from ancient samples. They describe a detailed survey of Neanderthal remains, in which they examined 70 different bone and tooth samples for DNA content and contamination. After rejecting most as poorly preserved, they screened six for Neanderthal-specific DNA. Most showed high amounts of contamination by human sequences, but a 38,000 year old sample from Croatia provided over 90 percent Neanderthal sequences. All the work was done using this individual.
Using a new sequencing technique that amplifies single molecules for characterization, they obtained over a quarter-million unique sequences. Nearly 80 percent of these came from unknown sources, which is apparently typical of samples of this age. Most of the rest were equally divided between DNA from soil bacteria and primate sequences. Overall, there were nearly 16,000 individual pieces of primate DNA sequenced. One of the things that quickly became clear was that this DNA had suffered some damage over the years. Attempts to estimate its age relative to humans suggested that the Neanderthal lineage was twice as old that of modern humans, which makes very little sense when you consider that we've outlived them.
A different method of sequencing, which examined populations of DNA molecules (instead of single examples) was used to look at the same sequences. In these populations, the damage should average out—sure enough, 14 of the 34 bases that looked different were the products of damage. Eleven of these were the result of known forms of age-related damage, so they provide information that should help in interpreting the rest of the sequences. It's also worth noting that both the human and Neanderthal sequences are so close to the chimps that, should a Neanderthal sequence look different from both the human and chimp version, chances were good that it was an error, rather than a real difference.
Overall, sequencing reads produced a million bases worth of sequence (.04 percent of the human genome), with sequences available on every chromosome (including the Y – that's Mr. Neanderthal to you!). The group that reports its results in Science worked in collaboration on the same Neanderthal sample, but used a different technique, one in which the Neanderthal DNA is inserted into bacteria, which make multiple copies of a single fragment. It's a slower technique—only 65,000 bases were sequenced—but the same DNA can be obtained from the bacteria as needed, allowing for a higher degree of error correction.
Overall, their results were remarkably similar. One put the split between humans and Neanderthals at 450,000 and 570,000 years ago, the other somewhat earlier. Because these dates are derived in part from the date of hominid-chimp separation, there's a significant error in them that results from uncertainty regarding when the split with chimps actually took place. Both, however, are consistent with the fossil evidence. The sequences reveal very few differences—human and Neanderthal DNA appear to be 99.5 percent identical. One group suggested there was a hint of mixing between human and Neanderthal genomes, while the other found none, but both recognize that the data set is just not large enough to give a definitive answer at this point. In both cases, the data's still too sparse to say anything significant: most of it is in the form of 50-100 base fragments with kilobases of intervening sequences.
Mostly, the papers serve as a status report, one that leaves both groups optimistic for the future, although they plan on taking different paths to it. The group using the high-volume method intends to forge on along their current path in the expectation that two years' worth of similar progress will net a rough draft of the entire Neanderthal genome. The group that published in Science demonstrated that they were able to pull specific sequences near genes known to regulate developmental processes with reasonable success (29/35 worked), and plan on using that technique to try to fish out sequences that are notably different between humans and chimps. Although there won't be any Neanderthals around to appreciate their legacy being uncovered, it's possible that these results will help us find a little bit of Neanderthal in all of us.