We all carry Neanderthal DNA, which tells us who our extinct relatives were but has little impact on who we are. The genetic information found in all cells of the human body creates the basis for appearance, physiology and behaviour. The same information tells the history of our ancestors and the secrets of human evolution. An analysis of the genomes of 27,566 Icelanders now provides the most detailed information on the traces Neanderthals left in the human genome 50,000 years ago. This Neanderthal heritage comprises 2% of every Eurasian genome, and this study shows that it has little impact on human biology and disease. The analysis provided new interesting knowledge about the lives of Neanderthals and other unexpected ancestors and how humans met them.
All humans are genetically unique. Most of the genetic code we carry comes from our Homo sapiens ancestors.
All human populations outside Africa trace their ancestry back to a group that travelled outside that continent 60,000 years ago and later populated the rest of the world. Although the genomes of non-African descendants come from that Homo sapiens group, a small portion of about 2% derives from archaic humans: the Neanderthals. This is because after they left Africa, modern humans and Neanderthals had descendants, probably in the Middle East. An international research team has compiled new insights into the Neanderthal nature from the fragments left in our genomes 50,000 years ago.
“We have found pieces of the Neanderthal puzzle by scanning through the genomes of more than 27,000 Icelanders. Because we find different pieces in each person, we were able to reconstruct 50% of the Neanderthal genome. Previous studies implied that these fragments were associated with an increased risk of disease (such as propensity to diabetes, depression and higher addiction to nicotine), but our new study suggests that the Neanderthal genome has had less impact on our health today than previously thought,” explains Mikkel Heide Schierup, Professor, Bioinformatics Research Centre (BiRC), Aarhus University.
A better picture
Postdoctoral fellow Laurits Skov of BiRC developed this relatively new method for tracing archaic fragments of genomes from Neanderthals, and this comprised the basis for the new study. He and Moisès Coll Macià, a PhD student at BiRC, took the new method to Iceland, where the biopharmaceutical company deCODE Genetics has genetic data and health information for more than half the population.
“deCODE Genetics has the world’s best and largest genomic data set. An example of this is that they know which gene copy comes from the father and which from the mother. They also know phenotypical and health information for each sample such as height, blood cholesterol or depression. By combining deCODE Genetics’ data and expertise with our new method, we started a project 10 times larger than previous studies of Neanderthal DNA in the human genome,” explains Laurits Skov.
The researchers tried to associate Neanderthal sequences with various physical traits or increased disease incidence from the deCODE database. Unlike previous studies, they found that the Neanderthal DNA within Icelanders has little impact on human biology.
“Many of the Neanderthal mutations previously found in the modern human genome have been thought to be associated with increased risk of disease. But our study shows that human gene variants located right next to the Neanderthal genes explain this increased risk much better,” says Moisès Coll Macià.
The traits and diseases that Neanderthal content does affect reported in this study are a slightly lower risk of prostate cancer, lower concentration of haemoglobin, shorter height and slightly faster coagulation of blood plasma.
Other archaic humans on the scene
Among all fragments, the researchers found that a non-negligible part were more associated with another prehistoric human rather than the Neanderthals: the Denisovans.
“So far, Denisovan genes have mainly been found among Australian Aborigines, people from eastern Asia and people in Papua New Guinea. To explain this Denisovan component in Iceland, we think that Neanderthals had descendants with Denisovans before they met Homo sapiens, and they transferred both Neanderthal and Denisovan DNA to the children,” explains Mikkel Heide Schierup.
Another possibility is that Homo sapiens met Denisovans long before modern humans met Neanderthals.
“Both explanations are equally likely, and both explanations are a great surprise. It is well known that a group of our ancestors left Africa and met Neanderthals in Europe about 50,000 years ago and mixed. However, it is a great surprise that either of these groups also had descendants with Denisovans, who lived in a very distant area (Siberia), and this is relevant scientific news,” says Mikkel Heide Schierup.
Older mothers and younger fathers
One major feature of the high quality of the deCODE data is the ability to distinguish which of the two copies of an individual’s DNA come from the father and which from the mother. When one of the DNA copies contained a Neanderthal sequence and the other a human sequence – for the same genomic positions – the researchers were able to compare modern humans and Neanderthals face to face. Based on the difference in the number and type of mutations accumulating differently in modern humans and Neanderthal fragments, the study reveals new information about the parental age of these two human groups.
“The analysis suggests that, 100,000 to 500,000 years ago, Neanderthal women became mothers on average at a later age than contemporary Homo sapiens women did in Africa. In contrast, the Neanderthal men became fathers at a younger age than their modern African cousins,” says Moisès Coll Macià.
Almost a folk hero
The study was based on a total of 3 months of field studies at deCODE Genetics in Iceland by the two young researchers from Denmark, Laurits Skov and Moisès Coll Macià. The 3-month stay in Iceland was a rich learning experience for both, although they did not actually have to collect data, but only analyse and compare existing data.
“The study was far from a classic field study, and in fact we could easily have performed the analysis online – instead of going to Iceland. However, deCODE Genetics requires their investigators to be physically present to access their data, since data security is their top priority. In addition, they are very selective about who they collaborate with and for which studies,” explains Moisès Coll Macià.
deCODE Genetics has genetic data from more than 160,000 adult Icelanders, or more than half the population, at their headquarters in Reykjavik. The company was founded 25 years ago by neurologist Kári Stefánsson to use genetic data to develop new methods for identifying, treating and preventing diseases. Initially, you might think that a private company would meet great resistance in being the custodian of the genetic data of an entire population.
“In the taxi to deCODE Genetics, the driver virtually referred to Kári Stefánsson as a folk hero, and it dawned on us that the Icelanders consider deCODE Genetics to be a huge benefit for the country. I think they have been incredibly good at being both open and inclusive and using public events to show how the genetic studies can benefit Icelanders by improving personalized treatment in the future. Iceland can provide many lessons for other countries planning to do the same thing,” says Moisès Coll Macià.
“The nature of Neanderthal introgression revealed by 27,566 Icelandic genomes” has been published in Nature. In 2018, the Novo Nordisk Foundation awarded a grant to Mikkel Heide Schierup for the project The Extraordinary Evolution of Human Sex Chromosomes.