A phalanx (finger bone) excavated from the dig sites of Denisova caves in Siberia was found to have the potential to tell if a person is vulnerable to COVID19. People with a variable chromosomal region 3, through a statistical analysis, were found to be comparatively more vulnerable to the infamous virus. Svante Paabo, the founding director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology and the 2022 Nobel Prize winner, put forth this finding where he stated that the chromosomal region 3 has genetic elements indicated to be inherited from the European Neanderthals.
Among the Founders of Paleogenetics – Svante Paabo
Born in Sweden, Svante Paabo is a well known paleogeneticist (a scientist who studies genetic material preserved in the remains of ancient organisms; somewhat like the character of Dr. John Hammond from the 1993 classic movie Jurassic Park). Though there is a bunch of things he is known for, the top of the list is that he is the winner of the 2022 Nobel Prize for Physiology or Medicine. What catches the eye even more is that his father, Sune Bergstrom, shared the 1982 Nobel Prize in the very same field.
As stated at the official website of Nobel Prize committee, the prize has been awarded “for his discoveries concerning the genomes of extinct hominins and human evolution”. To shed some light on it, we must glance through the story in a bird’s-eye view.
Assuming that my audience is decently aware of the terms used in the animal classification system, the genus Homo (under which we fall as the sapiens species) is categorized under the tribe Hominini (which, in turn, falls under the family Hominidae or “the Great Apes”). The extinct hominins are called as “archaic humans“, which includes the various members of the genus Homo that were present on Earth before the emergence of modern human. As per African fossil records, modern human appeared around 200,000 years ago, while according to European fossil records, Neanderthals appeared around 230,000 years ago. Neanderthals are archaic humans and are now extinct. The last records of their presence dates back to around 30,000 years ago. Moving on to the geographics of their spread, modern humans emerged in Africa and dispersed throughout Eurasia, while Neanderthals lived in Europe, western Asia and the Middle East. If not apparent enough, then let me pinpoint that there is a temporal (time-based) and spatial overlap between the modern humans and Neanderthals. This definitely urged the long unanswered question of interbreeding among the two.
Paabo’s discovery links humans across centuries
To understand if there has been any sort of genetic mixing, there is a straightforward way – to compare the genomes. Human genome had already been sequenced in 2003, however the Neanderthal genome sequencing still needed a lot of work. My exposure in the field helps me partially answer the delay in terms of the availability of the source of DNA, purity of extraction and amount of DNA sample required to sequence. Once successfully extracted, amplification based techniques (conveniently Polymerase Chain Reaction) are used to increase the DNA sample in-hand, which is then optimized for sequencing via the available techniques.
The first draft of the Neanderthal genome was reported by the Max Planck Institute for Evolutionary Anthropology in 2009. In a parallel endeavour, Svante’s group recovered and sequenced DNA from a hominin finger phalanx in the year 2008. Sequencing analyses suggested that the excavated bone belonged to an unknown hominin they termed as “Denisovans” (since the excavation was done in Denisova caves in the Altai Mountains). Another hominin bone was recovered in 2010 and studied on the same grounds. Sample sequencing of this suggested that it belonged to the Neanderthals. Both the genome sequences obtained (2008 and 2010 excavated bones), were then compared to the human genome under Svante’s supervision. Based on unique DNA fragment markers (such as the presence of specific transversion patterns) and the spatial-temporal overlaps it was observed that the Denisovans, the Neanderthals and modern humans might have met and interbred which led to the gene flow observed among these hominin genomes.
The Real Word Implications
A Nature article published in the year 2020 brought to light a stark observation reporting a Neanderthal gene cluster being responsible for severity of infection by the COVID19 causing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This article by Svante Paabo also indicated that the gene cluster present on chromosome region 3 in humans is a “risk locus”, and that the given genetic imprint is found in 50% of the South Asians and 16% of the Europeans. The genomic comparison Paabo’s lab had previously done proved as an immense help in establishing a gene flow relation like this.
From the quick case-study-discussion above, you might have arrived at the conclusion that studying the gene flow patterns in hominins can guide us along the billion base pair long DNA of modern human to identify gene segments associated with diseases. My take on this has two aspects – first that as Darwin suggested a “common descent” which states that all living organisms evolved from the last universal common ancestor (LUCA), the appearance of an entirely new and unrelated species isn’t naturally possible. This brings a glimmer of hope, since even the infectious microorganisms we encounter today, or in the coming future, “have a history” on this planet. Animals like the hominins that have survived the unforgiving wrath of nature must have been “stronger”, in scientific terms they must have developed genetic adaptations which helped them survive (as per the survival of the fittest remark). You’d be mesmerized to notice that this “history” I’m talking about is actually inscribed on the DNA we inherit. DNA doesn’t just inherit, but it also preserves, changes stochastically (if necessary as per natural selection) and maintains the new information for future use (again, a random but realistic event). This brings me to my second remark which stresses that if our genome holds the archaic human DNA that makes us susceptible to some diseases (as in the case of COVID19), there is a similar possibility that our DNA holds the very weapon that can strengthen our immune system against pathogenic attacks.
There’s no doubt that your genome shields you from many such harms even without anyone knowing it. Efforts like Svante’s can help us learn from the mistakes, or in some cases, benefit from the wisdom our ancestors bestowed us with (within our genome).
Who has previously won the Nobel Prize in Biology?
In 2021, the prize was awarded to David Julius and Ardem Patapoutian “for their discoveries of receptors for temperature and touch”.
In 2020, the prize was awarded to Harvey J. Alter, Michael Houghton and Charles M. Rice “for the discovery of Hepatitis C virus”.
In 2019, the prize was awarded to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza “for their discoveries of how cells sense and adapt to oxygen availability”
In 2018, the prize was awarded to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation”
What about the rest of the Nobel Prizes awarded in 2022?
Nobel Prize In Physics 2022 | Alain Aspect, John Clauser And Anton Zeilinger Win Physics Nobel
Nobel Prize In Chemistry 2022 | Sharpless For The Second Time
Nobel Memorial Prize in Economic Sciences 2022 | US Trio Bags the Award
Having a keen interest in topics as this, I’d be leaving the links to some interesting reads here:
Prüfer, K., Racimo, F., Patterson, N. et al. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505, 43–49 (2014). https://doi.org/10.1038/nature12886
Sankararaman S, Patterson N, Li H, Pääbo S, Reich D (2012) The Date of Interbreeding between Neandertals and Modern Humans. PLoS Genet 8(10): e1002947. https://doi.org/10.1371/journal.pgen.1002947
Zeberg, H., Pääbo, S. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature 587, 610–612 (2020). https://doi.org/10.1038/s41586-020-2818-3
DNA as a Data Storage tool: The Future of Data Storage at SciLynk by Nandana J, Samridhi Singh and Akshat Mishra
How Evolution carves our present: Bipedalism – Evolution to Modern Day Walking at SciLynk by Abhijit Mahato
He is a Life Sciences Graduate from the University of Mumbai, DAE, Centre for Excellence in Basic Sciences. Writing a brief knit story to connect with people and using words instead of the usual bs, are the go-to choices under his sleeves. A keen follower of the religion of "football" and a firsthand witness of the busy subway station they call research, he sets out to take another look.