Where do humans come from?

What makes us distinctly different from our ancestors and the species with which we coexist today?

Svante Pääbo’s pioneering research has evolved a novel field, paleogenomics, which could illuminate such age-old questions about the origins of humanity.

Svante Pääbo is the acclaimed Nobel laureate in Physiology and Medicine in 2022. Through his work, Pääbo has uncovered the entire genome of the Neanderthal and discovered a previously unknown species, the Denisovan. Whilst archaic in nature, this information sheds light on the evolutionary history of the modern-day Homo sapiens’; highlighting both similarities and differences with the genetics of our ancient relatives.

Aware of the enormous task at hand, Pääbo began by sequencing mitochondrial Neanderthal DNA. Over the years, he refined his techniques in order to overcome the vast technical difficulties of sequencing such old DNA. Prone to degradation and contamination with modern substances, often only traces remain, limiting the reproducibility of any results. Eventually, a meticulous PCR-based method was established, with stringent preparation and monitoring of contemporary contaminants. 

In 2010, he became the first scientist to reveal the entire Neanderthal nuclear genome. Later, upon the discovery of a 40,000-year-old bone fragment in Siberia, sequencing reported a unique genome that was attributed to a novel species, the Denisovans.

Following comparative analyses, it was shown that modern day humans of European and Asian descent share 1-4% of their genome with Neanderthals. Similarly, it was found that populations in Melanesia and Southeast Asia share up to 6% of their DNA with Denisovans. When contextualised with the migratory movements of both populations, this suggests that Homo sapiens interbred with both Neanderthals and Denisovans. Estimates suggest that Homo sapiens first migrated out of Africa 70,000 years ago, encountering both species as they expanded north and eastwards.

So far, it has not been established whether extinct hominins interbred with Homo sapiens in Africa, as the climate does not favour the accurate preservation of DNA. However, evidence points that gene flow between the species likely occurred in Africa too.

Aside from postulations about the historical movements of hominins, Pääbo’s work also holds relevance today. Certain genes present in our ancestors remain abundant across the world, as homologies between both Neanderthals and Denisovans with Homo sapiens were found. For example, multiple haplotypes that dictate the risk for severe illness under SARS-CoV-2 were found to be inherited from Neanderthals. Similarly, EPAS1, a Denisovan gene controlling the response to high altitude, enables some Tibetans to survive in harsh climates.

The differences in the genomes of Homo sapiens and its extinct ancestors are also profoundly significant. Ongoing research is exploring the complex phenotypic implications which arise from these genetic differences, on the premise that such characteristics may be responsible for the longevity and dominance of Homo sapiens.

Interestingly, a disproportionate number of genes affected by amino acid changes are involved in the development of the brain in modern humans, suggesting that increasing complexity of the brain was positively selected for in evolution; possibly one of the attributes to which the modern human owes its success. In the case of a different gene, FOXP2, which encodes a transcription factor, it has been shown that certain amino acid substitutions in the gene are common to both the anatomically modern human and its archaic ancestors. However, a change to an intron in the gene, affecting its expression in some tissues, occurred after the genetic divergence of modern humans.

Pääbo’s findings, a product of decades of curiosity- driven perseverance, provide groundbreaking insight into the origins of humanity, and generate ample excitement about the potential of paleogenomics. 

Image: Sangharsh Lohakare on Unsplash