Everybody loves Neandertals, those big-brained brutes we supposedly outcompeted and ultimately replaced using our sharp tongues and quick, delicate minds. But did we really, though? Is it mathematically possible that we could yet be them, and they us?
By the same token, could not the impossibly singular Mitochondrial Eve, her contemporary Y-chromosome Adam, and even the “Out of Africa” hypothesis simply be convenient fictions paleogeneticists tell each other at conferences to give their largely arbitrary haplotype designations and subsequently derived evolutionary trees more credence?
Perhaps one of the best ways to try to answer this question is to ask what the coronavirus has to say about the issue. Svante Pääbo, director of the genetics department at the Max Planck Institute certainly believes that Homo sapiens Neanderthalensis, or just Homo Neanderthalensis, if you prefer, is extinct. Pääbo, the son of 1982 Noble laureate Sune Bergström, has made a nice living off of Neandertal bones, finding gene after gene that is distinctly “Neandertal.” In 1997, Pääbo successfully sequenced mitochondrial DNA from a specimen found in Feldhofer grotto in the Neander valley. Fast-forwarding past a few recent PR disasters, the Germans were able to capture the productive Swede and set him upon the task of dealing with these inconvenient heirloom skeletons that kept showing up.
This September, Pääbo and colleague Hugo Zeberg announced that the major genetic risk factor for severe COVID-19 is inherited from Neanderthals. (We note that Nature publications prefer to include the h.) By any measure, this is a bold statement. The team found that severe COVID-19 disease is associated with specific genetic variants in six genes within a 50K-base-pair-long region of chromosome 3 that derived directly from a Neanderthal heritage. Similar investigations have also identified a protective Neanderthal haplotype on chromosome (chr) 12 that reduces the risk of severe COVID-9, and a protective region on chromosome 9 that is associated with the ABO blood groups.
Not content to rest on their laurels, Pääbo and Zeberg have just kicked things up a notch. The pair recently reported on the bioRxiv preprint server that another exclusively Neandertal variant, this time in the promoter region of the DPP4 gene at chr2q24.2, is really pulling the strings on COVID susceptibility. DPP4 is a widely expressed extracellular dipeptidyl peptidase involved in immune function and glucose metabolism. As it happens, DPP4 is also the receptor gene for the MERS coronavirus. Now we are getting somewhere.
Image Credit: Wikipedia
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