Proteins in dental enamel shed new light on human history

Breaking new ground 31. mar 2020 4 min Lektor v. EvoGenomics Enrico Cappellini Written by Kristian Sjøgren

Researchers from the University of Copenhagen have studied 800,000-year-old dental enamel from our distant relatives to obtain unique insight into human history. One of the researchers says that the proteins from dental enamel can help to develop our collective family tree.

A relative of humans called Homo antecessor lived in what is now Spain 800,000 years ago.

These human predecessors, which scientists initially thought were our direct ancestors, belonged to a closely related sister group in our evolutionary family tree. This is demonstrated by new research from the University of Copenhagen that may help to rewrite our entire ancient history.

The researchers behind the discovery have used proteins in dental enamel to construct the oldest genetic profile of prehistoric humans so far.

In fact, the record used to be 400,000 years, and this has now doubled.

“Now we can examine our genetic relationship with other prehistoric humans and distant relatives almost 1 million years back in time. This enables us to construct a family tree much more accurately than with the morphological studies used so far,” explains Enrico Cappellini, Associate Professor, Section for Evolutionary Genomics, Globe Institute, University of Copenhagen.

The discovery has been published in Nature.

Revolutionary technique sheds new light on prehistoric primates and rhinoceroses

The 800,000-year-old genetic information in the form of protein sequences has been discovered because the researchers from the University of Copenhagen have developed a method for extracting and analysing proteins from ancient dental enamel.

Sciencenews published an article describing this method, which the researchers used to confirm the relationship between a long-extinct rhinoceros and its modern descendants.

The researchers also used this method to confirm the relationship between a gigantic prehistoric ape and all living primates.

In the study on prehistoric apes, the researchers examined dental enamel from a 1.9 million-year-old fossil and confirmed that the gigantic ape Gigantopithecus, which could weigh up to 600 kg, was closely related to today’s orangutans.

“The 1.9 million-year-old Gigantopithecus proteins are the oldest-recorded genetic information ever discovered and used to establish relationships between species,” explains Enrico Cappellini.

Seven 800,000-year-old proteins found in dental enamel

In the new study, the researchers used the method to reconstruct the amino acid sequences of seven proteins from Homo antecessor.

The researchers compared the amino acid sequences of the seven proteins with similar sequences from modern humans, Homo heidelbergensis and Neanderthals.

The researchers examined differences between the amino acid sequences in the proteins and used these to determine the relationship between them. This enabled them to conclude whether Homo antecessor was a sister group close to our own lineage.

“In 1997, when the remains of a Homo antecessor were discovered, they were thought to be our direct ancestors. Since then, other studies have questioned this conclusion. The first genetic study of this species demonstrates that we modern humans, Homo antecessor, Neanderthals and Denisovans are closely related,” says Enrico Cappellini.

Compared genomes with proteins

The researchers did not actually examine dental enamel from modern humans, Neanderthals or Homo heidelbergensis at all.

Instead, they started with whole-genome sequencing.

By translating the genetic information in the DNA into proteins, the researchers compared the proteins of Homo antecessor with proteins derived from the other human species.

“We have examined data that are already publicly available on the genomes of other human species. But DNA surviving as long as the proteins in dental enamel is almost inconceivable, so we have to find proteins in older fossils to determine anything about their genetics or compare them with more recent species,” explains Enrico Cappellini.

Proteins confirmed that the prehistoric human was a man

The proteins from the dental enamel of Homo antecessor can be used for other purposes than just determining their relationship with modern or extinct human species.

One thing the researchers concluded was that the dental enamel they examined came from a man.

Two of the proteins in the dental enamel differ between men and women.

This is because one of the proteins is encoded by the sex chromosomes, and men have a Y and an X chromosome, while women have two X chromosomes.

“The fact that we found two isoforms – functionally similar proteins – in the dental enamel indicates that the molar come from a man and not a woman. Conversely, if we find only one isoform, we cannot definitely say that the enamel comes from a woman. This may also happen because we simply cannot find the male isoform of the protein,” says Enrico Cappellini.

Discovering more proteins to improve understanding of our ancestors and distant relatives

The researchers from the University of Copenhagen plan to develop their method so they can look back further in time and extract more genetic information from fossils.

This genetic information in dental enamel is relatively limited because the number of proteins is so small. The researchers therefore also want to determine whether they can extract proteins from bones.

“Finding proteins in other bones would be extremely interesting. The more proteins we can extract from the fossils, the more we can say about the prehistoric humans, and the more easily we can construct our own family tree for the time since we diverged from the chimpanzees between 7 and 9 million years ago,” explains Enrico Cappellini.

A very excited colleague

The new study is very exciting, according to Mikkel Heide Schierup, Professor, Bioinformatics Research Centre (BIRC), Aarhus University.

Mikkel Heide Schierup was not involved in the research, but he has read the article and is very excited.

“We will never be able to find DNA that is that old, and this therefore provides opportunities to start answering some really interesting questions about our ancestors. I am sure that this will launch a series of studies from the same research group,” says Mikkel Heide Schierup.

In particular, Mikkel Heide Schierup is pleased that Homo florensis, also known informally as the hobbit, is being investigated and put in its rightful place in our family tree.

“I imagine the researchers are already looking into this, because it makes sense to explore whether this human relative was Homo erectus or just a modern human being that looked a bit strange. Morphological studies have difficulty in determining this with certainty, but this method may make it possible. I am really looking forward to the results,” says Mikkel Heide Schierup.

Looking back even further into human history

Enrico Cappellini says that the researchers are hoping and planning to look even further back into the human past than the 800,000 years they have managed so far.

With Gigantopithecus, they looked back 1.9 million years, and initially the researchers would like to look just as far back into human history for human relatives such as Homo erectus and Australopithecus.

“So far, these species have only been characterized and related to our family tree through morphological studies of their bones and skulls. By putting a genetic profile on them, we can much more accurately relate them to the other species in the family tree and make this much more robust when we look back into our own past. So far, our record is 1.9 million years, and we can probably recreate that in studies of human dental enamel,” says Enrico Cappellini.

Enrico Cappellini says that initially examining human relatives originating in South Africa makes the most sense, since the climatic conditions in the past millions of years have been more favourable there for preserving genetic information such as proteins.

The dental proteome of Homo antecessor” has been published in Nature. Several co-authors are employed at the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.

I use high-resolution mass spectrometry (MS) to sequence ancient protein residues recovered from paleontological and cultural heritage materials. I am...

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