Cutting edge: Why Paabo’s findings are crucial to understanding how modern-day humans evolved?

This year’s Nobel prize for medicine has been awarded for genetic research on human evolution. Swedish scient Svante Paabo, who is known for sequencing the genome of extinct species, has been awarded the Nobel Prize for his groundbreaking research comparing the genome of modern humans and our closest extinct relatives.
What did Paabo’s research on sequencing the genome of the extinct species show?
First, Paabo uncovered the genome sequence of human’s closest extinct relative, the Neanderthal. This was followed the discovery of another extinct species Denisova. His research has established during the period of co-exence humans had mingled with Neanderthal as well as Denisova ——— that resulted in the transfer of genetic material of extinct species into present-day humans. In essence, through his landmark research, we now know that humans carry about 1-2 percent of DNA from Neanderthal.
For instance, his research showed that between 1 and 4% of the genetic material of people from Eurasia – where the humans heading out of Africa first interacted with Neanderthals. Put together, the inherited genetic material makes up about 40% of the Neanderthal genome. Similarly, around 4 to 6% of the genetic material of Melanesians – indigenous people of the region ranging from Indonesia to Papua New Guinea, Vanuatu, and Fiji – comes from Denisovans.
Why is this important?
First, because of his discoveries, we are able to understand what makes humans different and unique from their close extinct relatives.
It is important because the inherited genes affect our physiology (the physical body) to this day. Take, for example, the Denisovan EPAS1 gene inherited Tibetans – and in a very low-frequency Han Chinese — gives them a survival advantage.

Another inherited cluster of genes known to be involved in microbial recognition and allergic reactions is found in surprisingly high frequencies in the modern humans, suggesting that it has favourable outcomes.
More recently, one of his studies showed that a gene inherited from Neanderthals could influence the risk of respiratory failure in those with Sars-CoV-2. Humans have inherited non-disease genes that affect our pigmentation or sleep patterns from these ancient beings as well.
Clues of our origin
The ability to compare the modern human genomic sequence and that of the ancient hominins also allows us to understand what makes us humans. Unlike Neanderthals who also had big brains, lived in groups, and used tools, modern humans were able to create complex cultures, develop technologies, create art, and cross open water to spread to all parts of the planet. Researchers believe there could be clues in the genomes as to why homo sapiens flourished while the other species went extinct.

Paablo’s work has also enabled researchers to refine the Out of Africa model, in which all modern humans are traced back into Africa in an unbroken line, adding that interbreeding occurred between ancient and modern humans.
How Paabo made it possible to sequence ancient genomes?
Fuelled a strong interest in Egyptology, Paabo has been trying to sequence ancient genomes since he was a graduate student. His work not only resulted in the finding of the hominin Denisovans but also led to the establishment of a new scientific discipline called paleogenomics.
Unlike the human genomes or that of Sars-CoV-2 being sequenced at an increasingly fast pace now, sequencing the DNA from samples tens of thousands of years old is riddles with challenges – the DNA is chemically modified and degrades over the years with only trace amounts remaining and the remaining DNA is contaminated with DNA from modern humans and microbes.
Seemingly an impossible task, Paabo devised various methods to ensure only the genomes of the ancient relatives are read when the samples are sequenced. At first, he started sequencing the DNA from Neanderthal mitochondria – instead of the more detailed DNA sequence found in the nucleus of the cells – because it is present in thousands of copies, there increasing the chance of success. Not only could this method sequence fewer base pairs of the DNA, it also presented the challenge of parts being lost – mitochondrial DNA is passed exclusively through the maternal line, and fragments would be lost if a woman has sons.
Later on, DNA amplification and more powerful sequencing methods ensured that his team could sequence the small fragments of the nucleus DNA. But it also compounded the problem of contamination. To remove contamination, he started to look at sites in the genome that are different in Neanderthals and modern humans, using sites where present-day humans differ from both chimpanzees and Neanderthals and looking for male contamination in female Neanderthal samples using unchanging parts of the Y chromosome.
Using these techniques he was able to complete a full Neanderthal genome with 3 billion base pairs (similar to humans).
“I think it’s interesting to think about if Neanderthals had survived another 40 thousand years, how would that influence us? Would we see even worse racism against Neanderthals, because they were really in some sense different from us? Or would we actually see our place in the living world quite in a different way when we would have other forms of humans there that are very like us but still different. We wouldn’t make this very clear dinction between animals and humans that we do so easily today,” said Paabo in an interview with the Nobel Prize website.