The ability to sequence ancient DNA derived from human fossils has revolutionised our understanding of human evolution. It shed light on how we interacted with other human populations, such as Neanderthals and Denisovans. It also provided us with valuable insight into the relationship between our genetic make-up, circulating pathogens and evolutionary selection. “For the first time, researchers were able to answer some questions on human history using phylogenetically useful biomolecules from our ancient past,” says Frido Welker, an assistant professor at the University of Copenhagen. Yet despite these scientific breakthroughs, DNA does have its limitations. “The problem with DNA is that it doesn’t survive very long – just several tens of thousands of years,” adds Welker. “At least from an evolutionary perspective, this means we have a small window to study human evolution directly, without having to infer backwards into the past.” To remedy this shortcoming, Welker advocates using ancient proteins recovered from hominin fossils. With the support of the EU-funded HOPE project, he has successfully demonstrated the feasibility of doing exactly that.
The tell-tale protein
The idea of using proteins to research evolutionary history emerged during earlier work, when Welker and colleagues found that ancient animal fossils preserved informative protein sequences. During this work, he realised that if hominin protein sequences could be reliably analysed, they had the potential of being phylogenetically informative. “As proteins are comprised of an amino acid sequence that is determined by the protein-coding DNA sequences in the genome, they too can be phylogenetically informative,” he explains. “Even better, these proteins survive well beyond the lifespan of ancient DNA.” In the HOPE project, which received support from the Marie Skłodowska-Curie Actions programme, Welker aimed to clearly demonstrate the feasibility of this approach using several hominin fossils that dated beyond the preservation limit of ancient DNA. “Accurately determining amino acid sequences is difficult, especially for ancient proteins,” notes Welker. For example, one challenge researchers faced was that these ancient sequences are often modified and fragmented, and might be different from any available reference sequence. Researchers also had to deal with modern protein contamination, which can occur during archaeological excavations and subsequent handling during collection and laboratory analyses.
An exciting period of evolution
To overcome these challenges, the team developed new chemical and computational approaches. “Although certainly not perfect, these approaches gave us confidence that the sequences we used for phylogenetic analysis were endogenous to the fossils and likely represented the correct amino acid sequence,” adds Welker. The approach worked: “We were able to demonstrate how ancient proteins preserved in enamel survive for at least 2 million years in both temperate and tropical areas,” he says. “This in turn allowed us to sequence proteins from ancient fauna, an extinct great ape and two extinct human species – Homo erectus and Homo antecessor.” Challenging the presumption that ancient proteins are phylogenetically uninteresting, the HOPE project has provided a new approach to studying human evolution. Welker is now expanding on this approach through the PROSPER project, which is dedicated to applying some of the work done during the HOPE project to the last 1 million years of human evolution. “This is a really exciting period of human evolution, and one where ancient protein analysis can provide some important biological solutions,” concludes Welker.
HOPE, proteins, human evolution, evolution, fossils, DNA, protein sequences, phylogenetic