Mmmm…that's good Neandertal protein in them bones

4 minute read

A press release from Washington University describes recent work in extracting and sequencing a bone protein from two of the Shanidar Neandertals. The work is a collaboration of Erik Trinkaus, Ivor Karavanic, and scientists at the Max Planck Institute for Evolutionary Anthropology.

The paper has been published in the PNAS Early Access bin. Apparently they attempted to extract protein from Shanidar 2, 4, and 6, as well as Vindija Vi-76/228, but only succeeded in Shanidar 2 and 6. The protein was osteocalcin, which is the second-most abundant protein in bone. The Neandertal amino acid sequences were identical to the human sequences, which themselves do not differ from chimpanzees or orangutans. It is not reported whether there are allelic differences among humans or any of those other species. Gorillas have a sequence that differs from other hominoids at one position, similar to monkeys.

This study is a first, because protein sequence recovery from fossils this ancient has never succeeded, although previous attempts were made to obtain bone collagen from fossil remains. Apparently the chemical characteristics of osteocalcin in particular aided in its preservation by resisting diagenetic breakdown.

This study has sort of a "gee, who'd a thunk it" interest, but otherwise it seems to me like a waste of good samples. There is really no hypothesis that are likely to be tested by protein sequences taken from Neandertal fossils. Consider:

  1. The proteins preserved in bone are by and large structural proteins like collagen and this protein, osteocalcin. These structural proteins have essentially the same function in the bones of all hominoids, so there is little chance that there will be important adaptive changes among them.
  2. Human functional genes tend to have genealogies extending back a million years or more. This means that for most functional genes, Neandertals almost certainly would have had alleles within the modern human range of variability. This is more true for protein sequences than for nucleotide sequences, since the possibility of rare neutral variants is substantially lower for amino acid changes.
  3. Unlike genes, proteins appear only in the tissues where they are active. Functional protein differences between humans and Neandertals are very likely either to be developmental signalling proteins active early in ontogeny, or structural and regulatory proteins of the central nervous system. Neither of these classes of protein is likely to be preserved in Neandertal fossil bone.
  4. It is still not known how most differences in amino acid sequence between protein products arise. Considering that there are only 20,000 or so human genes and many more proteins, it follows that there must be several similar proteins created by each gene through posttranslation processing. So for proteins that are substantially rarer and less bound than structural proteins, there will likely be doubt about whether the same gene product is being compared when differences occur.

When people have talked about fossil protein sequences before, they have usually had in mind the potential recovery of dinosaur proteins or other similarly ancient groups. In that case, the recovery of a structural protein might potentially be helpful for phylogeny, because the relationships with living taxa are so distant that many amino acid changes will have occurred. Likewise, there is some possibility (albeit slim) that a structural protein from a dinosaur might give some information about dinosaur metabolism, such as whether they grew quickly or were warm-blooded.

For Neandertals or any other ancient human group, there is really no information like this to be had. And even in this case, the human and chimpanzee osteocalcin protein are the same, so there is every expectation that the Neandertal protein would also be the same. One may point to the osteocalcin difference between gorillas and the other hominoids as an exception, but it is far from clear that this is an adaptive difference or that it speaks to the presence of adaptive differences in structural proteins generally. The story presented in the paper is that the gorillas may have more dietary vitamin C, and so retain the amino acid sequence of most mammals, while the other hominoids needed the ability to synthesize the protein in the absence of vitamin C. As yet, it is unclear what has to be explained here, since the sequence in most mammals is obviously unavailable (this study presents only "monkey" and "cow". Even so, most mammals do not have a gorilla-like diet -- including the monkey in the study (Macaca fascicularis). And chimpanzees and gorillas in regions where they are sympatric eat mostly the same species, differing mainly in fallback foods.

And if this is the kind of hypothesis that can be tested with this work, then clearly the answer is to find out how the protein functions in living mammals first. This means going beyond the comparisons of living hominoids, monkeys and cows, to sequence mammals that present phylogenetic contrasts in diet. We can almost certainly predict beforehand that no fossil specimen of Homo is going to be different from living humans or chimpanzees. If we can show phylogenetic contrasts between other mammals in this amino acid sequence based on diet, then there is some reason to think that some australopithecines might show a difference. In which case it would be worthwhile to grind some australopithecine bone samples to find the answer. But this shouldn't be done on a whim, but only after comparative studies in mammals show that there is some reasonable chance of an interesting result.

This has turned into a bit of a rant, but please stop letting graduate students grind up our fossils! It is not worth losing rare organic samples just to explore every empirical unknown. Every empirical unknown is not a theoretical unknown, and this case in particular is one where the result could have been predicted in advance.