2021 Massry Prize Laureates
“The central role of population mixture in our species history”
“Using ancient epigenetics to study human evolution”
2021 Massry Prize for the Discovery of Ancient DNA
Clues to the origins of early human life are buried in deep sediments below the earth’s crust. By carbon dating fossils from many thousands of years ago, scientists have created a detailed family tree of human evolution. It starts about 10 million years ago with a common ancestor whose offspring developed into the hominins (humans and their extinct close ancestors), chimpanzees, gibbons and gorillas. The hominins continued to evolve with groups such as Australopithecus making an appearance about 4 million years ago, and then much more recently (about 300,000 years ago) Homo neanderthalensis and Homo sapiens, the anatomically modern human (us!). Through intensive study of skulls and bones, scientists have determined that there was an early migration of hominids out of Africa to Europe and western Asia that gave rise to Neanderthals, while Homo sapiens continued to evolve in Africa. There was a second wave of migration of homo sapiens about 30,000 years ago that went on to populate the entire world; but the relationship between them and the Neanderthals could not be established using fossilized bones alone. So how can we better understand the emergence of modern-day humans?
The Massry prize this year is awarded to three outstanding scientists who made discoveries that have shed new light on the origins of humans, in some cases overturning previous assumptions. Svante Pääbo and David Reich were fascinated by hominins, our direct cousins, and what they might tell us not only about our history but also our biology. Instead of looking at the bones, they looked within the bones at the remaining ancient DNA – the string of nucleotides contained in every cell that, along with our environment, determines who we are. Together, Pääbo and Reich made astounding technical advances. They developed some of the first methods to piece together ancient DNA that had been degraded over 50,000 years and mixed up with the DNA of other organisms that invaded the bone tissue. At the start they could only extract 3% or so of the human DNA but with continued innovation, they were soon recovering over 50% of human DNA from many different fossils. With this amount of data, they were able to re-build the genomes (the complete set of genetic material within the cell) of our ancient ancestors and cousins and compare them to modern Homo sapiens. They found that almost 30% of the Neanderthals’ genome can be identified in modern day humans. In other words, there was a lot of interaction between these groups in pre-historic times.
This turns out to have major implications for how Homo sapiens evolved and for medicine in general. For example, small genetic changes in a number of key genes found in Neanderthals turn out to make modern humans susceptible to diabetes. Neanderthals had more reason to be adapted to starvation which is what likely selected these changes, but these genetic changes are now a detriment with greater availability of high calorie diets in modern society. It also turns out that Tibetan’s have a specific gene variant from another group of ancient humans discovered in Western Asia (the Denisovans). This is an oxygen-sensing gene (note, we previously gave a Massry prize to the scientists who discovered this!) that allows them to function much better at high altitudes. Clearly, parts of the primitive human genome have both created trouble through making humans susceptible to certain chronic diseases, but in other cases helped humans cope with specific types of harsh environments. Very recently these amazing findings led to the discovery that humans with specific Neanderthal mutations are more prone to getting infected with SARS-CoV-2 – which is contributing to ideas of how to prevent such infections in the future.
DNA contains the code of life, but that code has to go through several steps of translation to create individual characteristics. One critical step is the regulation of DNA by methylation. Methylated DNA cannot be read and remains silent, while unmethylated DNA is read to yield the proteins that lead to real-life traits. Methylation can be regulated by environmental factors in real time – this process is called epigenetics. Dr. Liran Carmel reasoned that understanding methylation of ancient DNA could shed further light on which parts of the DNA was active from ancient humans and how ancient humans evolved and responded to their environments. He coined the term “paleo-epigenetics” and found about 900 regions of DNA regulation that were specific to modern humans. Interestingly many related to the development of the voice box and pharynx – a region of incredible importance to modern human speech and communication of complex ideas.
Together these discoveries by Pääbo, Reich and Carmel have revolutionized the study of human evolution and provided deeper insights into who we are and where we came from. The information has already demonstrated how past evolution has favored some traits that are not well adapted for our modern environment. The field will continue to have a major impact on our understanding of human biology and its underpinnings for human medicine.