By Helen Albert, Editor

Although archaeologists and anthropologists have been studying the ancient remains of our ancestors for many years, the study of ancient DNA extracted from these specimens began more recently. In 1984, Russell Higuchi, Allan Wilson and colleagues (University of California, Berkeley, USA) managed to extract DNA from a museum specimen of the Quagga, an extinct relative of the Zebra.

Over the next few years Svante Pääbo, one of the founders of paleogenetics, managed to extract DNA from mummified human samples that were thousands of years old. However, the field of ancient DNA really took off with the advent of the polymerase chain reaction (PCR) in the late 1980’s. After this, many research teams attempted to extract ancient DNA from a wide range of different samples with varying degrees of success

In the intervening years, the field has continued to advance and some of the initial problems associated with contamination and degradation of the DNA in ancient samples have been overcome, notably by Pääbo and his team at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. By 2004, mitochondrial DNA had been extracted from a number of Neanderthal fossil specimens across Europe by the Leipzig-based team and their collaborators and by 2010, Pääbo and colleagues had sequenced a draft version of the Neanderthal genome from bones found in the Vindija Cave in Croatia.

Last month, leaders in the field gathered at the Wellcome Genome Campus in Cambridgeshire for a new conference to celebrate recent advances and achievements in ancient DNA research from the last 30 years ­– Human Evolution: Fossils, Ancient and Modern Genomes.

The Denivosan identity

In 2010, DNA was extracted from a 41,000-year-old woman’s finger bone found in the Denisova Cave in southern Siberia. When researchers studied the mitochondrial DNA extracted from this sample they found it was different to both modern humans and Neanderthals, but that it shared a common ancestor from about 1 million years ago. This suggests that the woman was from a group of hominins that migrated out of Africa separately from the ancestors of both modern humans and Neanderthals.

Subsequent analysis suggests several teeth found in the same cave are from other ‘Denisovan’ individuals. But, unlike Neanderthals, the Denisovans are unique in so far being characterised by ancient DNA analysis rather than by large-scale physical fossil evidence.

Speaking at the conference, Liran Carmel (The Hebrew University of Jerusalem, Israel) explained that he and his colleagues investigated whether they could reconstruct Denisovan anatomy by mapping gene expression (via DNA methylation markers) in Neanderthals and chimpanzees.

Looking at expression of genes associated with appearance, they first tested whether they could use DNA methylation maps in chimpanzees and Neanderthals to accurately predict anatomical features, for example, midfacial prognathism (projecting facial features) in Neanderthals. They showed their method was approximately 84% accurate in identifying diverged traits and 82% accurate in predicting direction of change of the traits in the two species.

Using the same technique, the researchers looked at markers of methylation on the DNA extracted from the Denisovan samples. The resulting anatomical profile suggests that while they do share some traits with Neanderthals, such as a projecting face and large jaw, they also have other features such as an expansion in the cranium and differences in tooth size.

Interestingly, the Denisovan anatomy predicted by Carmel and colleagues fits the morphology of two recently discovered skulls in Xuchang China, suggesting that (as speculated) they may be from Denisovans.

 

How Neanderthal are we?

Since sequencing the Neanderthal genome, comparisons have been made with the DNA of modern humans and there is evidence to show that all modern, non-African people have retained at least 1-2% of their DNA from Neanderthals due to interbreeding at some point in the past.

The amount of Neanderthal DNA in the human genome has gone down over time, but a small percentage has remained.

Janet Kelso (Max Planck Institute for Evolutionary Anthropology, Leipzig), another speaker at the conference, explained that while some of this inherited ancestry may be harmful, some may be beneficial.

For example, inheritance of certain gene variations may have helped modern humans to develop a more effective immune system for fighting off disease and infection. The toll-like receptors (TLR) are proteins that play an important role in the innate immune system. Kelso and colleagues recently discovered a genetic cluster of three such receptors with specific combinations of variants (haplotypes) linked to the Neanderthal genome (TLR6, TLR1 and TLR10).

A study carried out by researchers at 23andMe showed that genetic variants in the same three TLR genes are also associated with asthma and allergies in modern humans, in that individuals with archaic genetic variants seem more likely to develop allergies.

Kelso commented that individuals with Neanderthal genetic variants seem to be less likely to have Helicobacter pylori infection or are able to fight it off better. But she said this is likely to be a proxy for pathogens in general and likely indicates increased efficacy of the immune system.

Neanderthal genes have also been linked to appearance. For example, a variant in the gene BNC2 found in Neanderthals is found at high frequency (~66%) in modern humans with pale skin that does not tan easily and is subject to freckling.

Behaviours have also been linked to inheritance of archaic genes. Kelso noted that being an ‘evening person’ seems to be linked to a Neanderthal genetic inheritance, which is probably linked to light exposure.

These are just two examples of the high calibre research presented at the Human Evolution conference, but they serve to illustrate how far the field has come in 30 years. They also demonstrate the dramatic impact that rapid advances in new generation sequencing technology have had on ancient DNA research, as well as highlighting the value that genetic information can bring to a field that previously relied solely on fossil discoveries to discover more about our evolution and ancestry.