Deciphering the DNA Code of Neanderthal Man

smooth wombat writes "U.S. and German scientists have embarked on a two-year long project to map the genetic code of Neanderthal man. Their hope is to gain a greater understanding of how modern human brains evolved. This study comes after last years completion of mapping the DNA of chimpanzees, our closest living relative." From the article: "Over two years, the scientists aim to reconstruct a draft of the 3 billion building blocks of the Neanderthal genome -- working with fossil samples from several individuals. They face the complication of working with 40,000-year-old samples, and of filtering out microbial DNA that contaminated them after death. Only about 5 percent of the DNA in the samples is actually Neanderthal DNA, Egholm estimated, but he and Rothberg said pilot experiments had convinced them that the decoding was feasible."

Comments

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[wheatking]

this and yesterday's article in NYT by the same author (Nicholas Wade) look like placed (indirectly paid for to some PR mavens) ads for 454 lifesciences (if named after the famous chevy engine, a helluva name for a company). 454, having built a fair-to-middling sequencer is trying hard to stay alive in a race to the $1000 genome that will not be won by them or solexa, another startup given their slow pace and limited read lengths of the base pairs. nothing new here. move on folks.

Definitive post on Neandertal Decoding

[kkamrani]

This link, "Announcing a two year Neandertal genome decoding project" links to several science blogger's take on this anouncement including a definited Neandertal sequencing post by John Hawks.

Re:Definitive post on Neandertal Decoding

[jd]

Definitely interesting, highly contradictory though. The blog directly linked to claims that the neandertal DNA is being found in the bacteria - that the bacteria had somehow made it a part of its own DNA. This seems highly improbable. Bacterial DNA can do strange things, but absorbing large chunks of neandertal DNA is almost certainly not one of them.

The other descriptions imply that it's contamination through questionable extraction techniques - they're grinding up the fossils, so ALL the DNA in the sample will be mixed together, and strands may well end up getting broken, making it much harder to sequence correctly.

Sequencing fossil DNA is certainly possible, and is extremely desirable, but the approach seems... odd. The BBC article, for example, claims that they're going to look for the genes that differentiate modern humans from neandertals, such as mental capacity. Given that we don't fully understand what "mental capacity" actually means, or indeed what mental capacity neandertals actually had, they would need to be looking for an unknown difference to identify an entirely theoretical and totally unquantifiable distinction. That's not good science.

Lastly, we know from studies of neandertal mtDNA that there was a large genetic diversity. Far larger than had been suspected, prior to that study. If these scientists are taking neandertal nucleic DNA from significantly different regions and/or times, they cannot be certain that the nucleic DNA had not evolved or otherwise differed to the point where direct comparison or simple in-lining of the genes would make no sense whatsoever.

This is a good research project, but I am highly uncertain of their methods and am not convinced it will yield meaningful results. Because repeat studies will be difficult to do, this is an area where those involved HAVE to take extra care to put their results beyond question. This care is NOT being taken, based on what I'm seeing.

Re:Definitive post on Neandertal Decoding

[jd]

You are correct, because they sequence directly. This isn't necessary for Neandertal DNA as we have plenty of reference points from chimp DNA and human DNA, which are already mapped. We only need to sequence those segments that are different from either.

There is an added problem. Most geneticists use chain termination sequencing, which is good for fairly decent lengths of DNA. 454 uses pyrosequencing which is faster but only good for much smaller lengths. When the unknown elements may contain repeats of unknown length, smaller sample sizes are a Bad Idea. If the sample size is smaller than the repeat, you will be incapable of knowing how long the repeat is and will therefore have multiple equally valid solutions to the analysis. This is Bad, since it is these differences the researchers are looking for.

There is an alternative technique (primer walking/chromosome walking) which works on much larger fragments and should be able to deal with the indeterminacy problem completely.

However, this all assumes that we need to use an existing method at all. We have two known points of reference (humans and chimps) and a ready supply of DNA from both. ALL we need to determine is what segments of Neandertal DNA do not match with either, and then sequence just those segments. What would be needed, then, is a genetic version of diff, as opposed to a genetic version of cat. DNA is ideally suited to producing diffs, because you can't connect non-matching bases, but is much harder to cat.

I'd say that it would make far more sense to do the fundamental research needed to develop new techniques that can exploit the fact that we have multiple known related species with mapped DNA, where the exact relationship with Neandertal is also known, but the differences created by that relationship are not. We have a gigantic library of knowns, which we can use to simplify the process. Instead, 454 is going to use an entirely random, utterly unsuitable method, simply because it's faster than developing a new method.

If people always stuck to the tools they already had, to avoid developing something more appropriate to the problem, we'd still be using stone tools and the closest to blogging anyone could get would be to find a really, really big wall to paint on.

Re:This is going to end badly

[MrFlibbs]

Don't laugh. Richard Dawkins predicts that "the missing link" will be born by the middle of this century. He has an essay on this in a book titled "The Next Fifty Years: Science in the First Half of the Twenty-first Century". This is an interesting book consisting of 25 speculative essays by leading scientists in various fields.

Dawkins' argument is that Moore's Law will eventually make the sequencing of genomes cheap enough to be routine. He speculates that a large database of hominid genomes plus expected advances in gene manipulation would support the creation of pre-human DNA. Once this is done, an implanted embryo with the new DNA could be inserted into a human womb, and out pops the new (old?) species. If Dawkins is correct, then other non-human species such as Neanderthals are also potentially viable.

In the essay, Dawkins briefly discusses the moral implications of such a task. He concludes that any objections are easily overcome by the great service to mankind in proving the correctness of the Theory of Evolution.

Re:Neanderthal Man went extinct because...

[bcrowell]

...the evolution of DNA in Homo Sapiens gave them a larger and more complex brain,
Nope, the average neanderthal had a bigger brain than the average human. However, both neanderthals and our own ancestors don't appear to have achieved any real level of culture until relatively recently in history; their artifacts don't show any specialization or innovation over tens of thousands of years, and they all come from local stone, indicating a lack of trade. The onset of culture didn't have anything to do with an increase in brain size (which didn't change over that short period). It may have had to do with something like the foxp2 gene, which is crucial for developing complex language. It's possible to make up a lot of stories, and nobody knows which is right. It's possible, for example, that humans first crowded out neanderthals because we were skinnier and could survive on less food, and only later developed speech and culture.

The cama.

[Savage-Rabbit]

Here's some background that isn't apparent from the article. The CNN piece talks about Neanderthals in the context of understanding brain evolution, but the million dollar question- in most scientists' minds- is whether Neanderthals and early modern humans interbred, after 500,000 years of separation. It seems at least possible: lions and tigers produce fertile offspring and they diverged 2 million years ago.

I have always had trouble understanding why some scientists flatly deny that interbreeding between Neanderthals and modern humans would have even been possible. Interbreeding between species seperated by longer periods of evolution than 2 million years is possible. Some boffins in Dubai actually managed to produce a living camel/lama hybrid. They had to use artificial insemenation but the result was a living hybrid (which they called a 'cama') and camels and lamas are seperated by 40 million years of evolution. It would seem to me that Neanderthals and modern humans probably could interbreed, in light of what history tells us about human nature it would be strange if they didn't and the only question is: Would the resulting individuals have been fertile? If they weren't it might explain why no Neanderthal DNA has survived in the modern human genome. I will certainly be interested in whether or not this DNA mapping/reconstruction effort succeeds.