More ponderings about proteins

Kia ora,

In April 2020 I published a post to this blog entitled "New Insights into Human Origins - Part 1", in which I discussed a research paper that had reported the sequencing of enamel proteins from an ca. 800,000 year old hominin tooth recovered from the Gran Dolina cave in the Atapuerca mountains in Spain. These proteins were about twice as old as what was then, and still is, the oldest hominin DNA ever sequenced. As I explained in that 2020 post:

"Proteins are biomolecules consisting of chains of organic compounds called amino acids that are assembled using information encoded in DNA, so the more similar two species' DNA is, the more similar we would expect the composition of their proteins to be. Proteins slower rate of degradation compared to DNA presents the opportunity to study hominin phylogeny (the evolutionary relationship between different species) further back in the past than is possible using DNA." 

Of course, this paragraph may erroneously have given the impression that proteins are a perfect substitute for DNA in this regard. As I noted in a subsequently added footnote to the 2020 post, less than 2% of our DNA contains information for creating proteins (a stretch of DNA that encodes for a protein is called a gene). The remaining >98% of our DNA (and the DNA of other hominins as well) is therefore invisible when proteins are all that are available. Over time this noncoding DNA tends to accumulate more mutations, or changes in its sequence, than DNA that codes for proteins and therefore is more useful for untangling evolutionary relationships between species. For example, the protein coding regions of the chimpanzee and human genomes are more similar than the noncoding parts. It does make sense when you take a moment to think about it. A mutation - even a change to a single base pair - in a DNA sequence that codes for a protein (essentially one of the building blocks of the body) is much more likely to have a deleterious impact on an individual's evolutionary fitness than a change to a sequence that doesn't code for anything, but which will still be passed on to any offspring. However, all that being said, proteins do tend to preserve much better than DNA, and as the old saying goes - beggars can't be choosy! 

The tooth from the Gran Dolina cave had previously been assigned to a species of hominin known as Homo antecessor. A comparison of the sequenced proteins with those from Homo sapiens (modern humans), Neanderthals, and Denisovans, which all shared a common ancestor as recently as the Middle Pleistocene (ca. 780,000 - 125,000 years ago), provided evidence that H. antecessor was a close sister lineage to these species. While the 2020 paper also reported the retrieval of proteins from a 1.77 million year old Homo erectus tooth from Dmanisi in Georgia, these sequences were more limited and able to give much less conclusive phylogenetic results.      

In a preprint paper posted on the bioRxiv server on 3 July this year, an international team of researchers, including several from the same labs involved in the 2020 paper, reports the sequencing of proteins from the tooth enamel of four ca. 2 million year old teeth from Swartkrans, a fossil-bearing limestone cave site in South Africa. These teeth had been assigned to the hominin species Paranthropus robustus. While only a small set of enamel proteins were sequenced some promising results were reported. 

Cast of a Paranthropus robustus skull (SK-48) from the Swartkrans site in South Africa. Image sourced here.

   

An artist's impression of what Paranthropus robustus might have looked like when alive. Image sourced here.  

The researchers were able to build a simple evolutionary tree based on the proteins that they sequenced. This tree placed the Paranthropus individuals outside of a grouping of Homo sapiens, Neanderthals, and Denisovans, confirming that these hominin species were all more closely related to each other than they are to the two-million-year-old Paranthropus. All of these species did, however, group more closely with each other than with chimpanzees, gorillas and orangutans. Although honestly, any other result would have raised a few eyebrows!

Additionally, based on one of the types of protein sequenced (amelogenin, a major protein constituent of tooth enamel), the researchers were able to determine the biological sex of the individuals to which the teeth belonged in at least two instances. Different versions of this protein - amelogenin-X and amelogenin-Y - are produced by genes on the X and Y sex chromosomes. The presence of amelogenin-Y in two of the four teeth led the researchers to unambiguously conclude that the teeth belonged to biological males. In one instance this contradicted a previous assignment to a female individual based on size of the tooth alone. The other two teeth, in which amelogenin-Y was not detected, were determined to most likely have belonged to biological females. Although not mentioned in my 2020 post, the presence of amelogenin-Y in the Gran Dolina tooth had also led to the conclusion that the tooth belonged to a biological male. 

Before I finish up, it is important to reiterate that the new paper is a preprint, meaning that it has yet to go through the process of peer review that traditionally precedes formal publication in a scholarly journal. However, when considered alongside the results of the 2020 paper these new results speak to the progress that has been made in even the last few years and the exciting potential of palaeoproteomics (the study of ancient proteins), though still a work in progress. 

Some additional commentary on this research, including opinions from experts, can be found in a Nature news article here. 

Thanks for reading,

Nick