July 17, 2009

Analysis of five Neandertal Genomes (Briggs et al. 2009)

This is a very exciting paper, both for the apparent advance in ancient DNA technology, and for the finding of a smaller effective population size for Neandertals. The reduced mtDNA diversity in Neandertals might be the result of selection. Even among current cold-adapted populations, mtDNA diversity is reduced, and this is due to bioenergetic adaptation for a cold climate.

Chemistry World has some details on the new technical advance:
Now, Pääbo and colleagues have created a quicker, less expensive, and less wasteful method to reconstruct the genomes of ancient specimens. 'The samples we used in this new project were even more poorly preserved than that original sample [analysed last year], meaning that the shotgun method would have cost hundreds of millions of pounds,' says graduate student Adrian Briggs who helped pioneer the new technique. 'Hence the need for our new targeted retrieval method - primer extension capture (PEC).'

'We have managed to immortalise a precious DNA source, for example a Neanderthal DNA extract, by making many thousands of copies of every original DNA molecule in that source,' says Briggs. In doing so, ancient DNA sequences can be stored in a 'library' they can be used again and again. The technique uses 5'- biotinylated oligonucleotide primers and a DNA polymerase that isolate Neanderthal mtDNA sequences from the plethora of contaminant DNA. Sequences of interest are then directly extracted from this amplified library of degraded DNA before the sequencing step. 'This saves on experimental time and costs by several thousand fold,' Briggs adds.

Eske Willerslev, an expert on ancient DNA at the University of Copenhagen, Denmark, thinks this is an important technological breakthrough. 'The capture approach makes it possible to retrieve very short pieces of DNA (50-70bp) that is difficult if not impossible using regular [ approaches,' he comments. 'This means that the chances of retrieving endogenous rather than contaminant DNA increases significantly.'
The much publicized Neandertal DNA data from Vindija cave were taken from an almost ideal sample in terms of preservation.

LiveScience has some details on the implications for the demography of Neandertals:
In fact, new genetic evidence from the remains of six Neanderthals (Homo neanderthalensis) suggests the population hovered at an average of 1,500 females of reproductive age in Europe between 38,000 and 70,000 years ago, with the maximum estimate of 3,500 such female Neanderthals.

"It seems they never really took off in Eurasia in the way modern humans did later," said study researcher Adrian Briggs of the Max-Planck Institute for Evolutionary Anthropology in Germany.

The research, which will be published in the July 17 issue of the journal Science, suggests the small population size of our ancestral cousins may have been a factor in their demise.

"Because there never really were millions of them, they probably were more susceptible to some event that made them go extinct, which to me, suspiciously coincides with the emergence of modern humans," Briggs told LiveScience.

Ian Tattersall, curator of anthropology at the American Museum of Natural History in New York, who was not involved in the current research, said the study "does support notions that toward the end of last ice age, the Neanderthal population was declining as a result of harsh circumstances." He added, "I don't believe Neanderthals would've gone extinct if it wasn't for this new element, the Homo sapiens competing for the same resources."
I really find it hard to believe that Neandertals died out beause of competition with Homo sapiens. After all, a population of a few thousand could quite easily have been accommodated in Paleolithic Europe; population density was so low, that there were plenty of resources for modern humans and Neandertals alike.

There are plenty of scenaria for the disappearance of the Neandertals, ranging from absorption by modern humans (although recent estimates of introgression are usually from modest to very low) to cannibalism, to contracting diseases brought by Homo sapiens and for which they had no immunity. We don't even know how long the co-existence between the species was before the disappearance of Neandertals. The argument for a causative role of modern humans in Neandertal demise is weakened if the latter persisted for many thousands of years after the arrival of the former.

If, however, Neandertals were so limited in numbers, perhaps there was no major reason for their disappearance. It could very well have been a statistical accident as random fluctuations in population size may have driven them to a non-viable demographic size from which they may not have been able to recover.

As usual for a Science paper, there are plentiful open access supplementary data.

Science doi:10.1126/science.1174462

Targeted Retrieval and Analysis of Five Neandertal mtDNA Genomes

Adrian W. Briggs et al.


Analysis of Neandertal DNA holds great potential for investigating the population history of this group of hominins, but progress has been limited due to the rarity of samples and damaged state of the DNA. We present a method of targeted ancient DNA sequence retrieval that greatly reduces sample destruction and sequencing demands and use this method to reconstruct the complete mitochondrial DNA (mtDNA) genomes of five Neandertals from across their geographic range. We find that mtDNA genetic diversity in Neandertals that lived 38,000 to 70,000 years ago was approximately one-third of that in contemporary modern humans. Together with analyses of mtDNA protein evolution, these data suggest that the long-term effective population size of Neandertals was smaller than that of modern humans and extant great apes.



Maju said...

Fascinating info, thanks.

I really find it hard to believe that Neandertals died out beause of competition with Homo sapiens. After all, a population of a few thousand could quite easily have been accommodated in Paleolithic Europe; population density was so low, that there were plenty of resources for modern humans and Neandertals alike.

I'd say that if "population density was so low" it was precisely because those were the figures the resources allowed for that kind of economy.

Along time there may be moments when population is suboptimal or exceeds the optimal figure. But, in the latter case, Malthusian brakes act as regulators - the population can never really grow above the viable figures without immediately decreasing due to scarcity and its derived high mortality. And when the population is suboptimal, natural demographic growth will soon make it reach the optimal figures.

And I don't think this would be different for Neanderthals. At most their economic system could have been somewhat different from ours (smaller foraging range for example). So I don't think the objection is valid (though maybe the speculated figures are not correct - can't say).

The Live Science article also says that The Neanderthals had about three times less genetic diversity than the modern humans.

I find this surprisingly high in fact. After all, modern humans are almost 7 billion people and even 50 kya H. sapiens already occupied more than three times the range of Neanderthals, what probably means that they were already more than three times their numbers.

The Other Jim said...

Even among current cold-adapted populations, mtDNA diversity is reduced, and this is due to bioenergetic adaptation for a cold climate.

Reduced mtDNA diversity in cold-adapted populations has not been demonstrated to be DUE to bioenergetic adaptation. This is a sexy hypothesis, but one not proven at all, and an active battlefield in the ongoing neutral / adaptive debates.

terryt said...

"This is a sexy hypothesis, but one not proven at all".

I agree. Reduced mtDNA diversity in cold-adapted populations is as likely to be a product of sequential periods of selection amoung migrants into such regions as being due to bioenergetic adaptation. Such selection would also account for the much reduced Neanderthal mtDNA diversity, especially as they seem to have been isolated from any genetic input for much more than 100,000 years if not half a million.

argiedude said...

Also equally interesting is their apparent technological breakthrough that allowed them to obtain DNA from much more degraded/contaminated Naenderthal remains than the Croatian sample sequenced earlier this year.

But I tried to understand the method in their supplementary file and couldn't. I saw something about neanderthal DNA having some distinctive thing about it that allowed their scanning machine to eliminate human contaminant sequences, reducing costs 100 fold or more. I dunno, it looks to be something that's going to produce big results in the future of ancient DNA testing. Can someone explain it? Also if it applies to just mtdna, or will it be useful for autosomal DNA, also?

Maju said...

They managed to clone the mtDNA like a thousand times for little cost, what allows as many replications as possible and rechecking the data as many times a need be without further extractions.

I do not understand the technological details though.