Nobel Prize in Physiology or Medicine 2022
Commented by Margarida Amaral, leader of the Functional Genomics and Proteostasis Research Group
The 2022 Nobel Prize in Physiology or Medicine will be awarded to the Swedish biologist Svante Pääbo for his discoveries concerning the genomes of extinct hominins and human evolution. Pääbo is a specialist in Evolutionary Genetics and one of the founders of paleogenomics. Since 1997, Pääbo is Director of the Genetics Department at the Max Planck Institute (MPI) for Evolutionary Anthropology, in Leipzig, Germany. The Department counts with 4 tenured faculty members (being Pääbo one) and two non-tenured members.
The main work that motivated this Nobel award consisted in the first draft of the genome of our archaic relatives, the Neanderthals in 2010, then completed in 2014 in high-quality by sequencing the genome of a Neanderthal woman from Siberia (both studies published in Nature [1], [2]). The latter study used a tiny hominid bone (toe phalanx) estimated to be over 50,000 years old to extract DNA.
Svante Pääbo
While still a student of Medicine at Uppsala University (Sweden), Svante Pääbo developed an interest in Egyptology. Thus, while carrying out his work in the human immune response to adenovirus, he also developed his secret project to isolate ancient DNA from a 2,400-year-old mummy sample. After a brief internship at the University of Zürich, Pääbo moved (in 1987) to the University of California, Berkeley to finally work on ancient DNA as a post-doctoral fellow. There, he worked at the lab of Allan Wilson, a pioneer in the use of genetic tools to study ancient hominid DNA and their relation to contemporary humans.
Svante Pääbo | Photo credit: Sylvio Tüpke, MPI for Evolutionary Anthropology
Technical aspects
Usually, the quality of ancient DNA is not very good, due to extensive fragmentation into very short, chemically damaged pieces and massive contamination with DNA from micro-organisms. However, ‘hard’ tissues (bones and teeth) usually offer the most convenient choice for ancient DNA extraction, as they minimize the degradation occurring in ‘soft’ tissues, while being less prone to contamination. In fact, one member of Pääbo’s department (Matthias Meyer) develops protocols to provide the highest DNA yields from highly degraded samples that maximize its analysis by PCR (polymerase chain reaction) amplification and high-throughput DNA sequencing technologies. Another member of Pääbo’s department (Janet Kelso) develops software approaches to optimize genome analyses so as to ensure that the ancient DNA sequences under study are reliable.
Discoveries
Using these molecular and computational technologies, Pääbo’s team found that the DNA present in the toe phalanx from the Siberian woman was very similar (in ~70%) to the modern human genome. Analysis of mitochondrial DNA (i.e., DNA present in the the energy producing organelles within cells) suggested that this specimen belonged to a Neanderthal. The details of the study are almost incredible, as it indicated that the Neanderthal woman was highly inbred, being the daughter of a very closely related mother and father (either half-siblings, or uncle and niece or aunt and nephew, grandparent and grandchild, or double first-cousins).
Many studies allowed comparisons among genomes of other hominids (e.g., the Denisovan genome a) and other many interesting findings. Though Denisovans and Neanderthals eventually died out, they left behind bits of their genes because they occasionally interbred with modern humans b. For example, it was estimated that 1.5-2.1% percent of the genomes of modern non-Africans can be traced to Neanderthals (see figure below). Denisovans also left genetic traces in modern humans, though only in some Oceanic and Asian populations (see figue below) like the Australian aborigines, (~6% Denisovan genes) or Han Chinese and Native Americans (~0.2 %). The Denisovan genes also appeared to ‘flow’ to a mysterious, 4th group of early humans in Eurasia (see figure below).
Figure | A possible model of gene flow events in the Late Pleistocene (extracted from [2])
Notes:
a The Denisovans are an extinct species of archaic human close but distinct from the Neanderthals and that ranged across Asia during the Lower and Middle Paleolithic.
b Neanderthals and modern humans are estimated to have coexisted in Europe and Asia for at least 30,000 years.
Impact
The relationship between Homo sapiens (modern humans) and extinct hominins has long been a topic of great interest. Pääbo’s pioneer studies allow us to understand the evolution of contemporary homo sapiens. Moreover, they also help identifying which genes played major positive roles in the ability of hominids to survive in the new environments after their expansion out of Africa (the continent that hosted the origin of our existence). In fact, a recent study by Pääbo reports that the major genetic risk for severe COVID-19 respiratory complications is inherited from Neanderthals [3].
Know more about this Nobel Prize here.
Get to know Svante Pääbo by watching his TED Talk on DNA, neanderthals and how closely related we are to our ancient ancestors here.