Can Covid-19 destroy Neanderthals?

Everyone loves Neanderthals, the big-brained brutes we cut off from assumptions and eventually transformed using our sharp tongues and quick, delicate minds. But we really, though? Is it mathematically possible that we can still be them, and that they are ours?

By the same token, the impossible singular mitochondrial eve, its contemporary y-chromosome Adam and the “out of Africa” ​​hypothesis may not even be compatible, as paleogenetists confer on each other their largely arbitrary haplotype positions at conventions. Trees more confident?

One of the best ways to try to answer this question is to ask what the coronavirus has to say on this issue. Sanvet Panbo, director of the genetics department at the Max Planck Institute, certainly believes that Homo sapiens Neanderthalnsis, or just Homo Neanderthalnsis, if you choose, is extinct. Pabo, son of Nobel laureate Sean Bergstrom in 1982, has lived a good life with Neanderthal bones, finding a gene after gene that is clearly “Neanderthal”. In 1997, Pabo successfully sequenced mitochondrial DNA from a sample found in the Feldhofer Grotto in the Neanderthal valley. Fast-forwarding, a few recent P.R. After the disasters, the Germans were able to capture the productive swede and entrust it with the task of dealing with this inconvenient inherited skeleton that kept showing.

This September, Pebbo and his partner Hugo Zeberg made the announcement The main genetic risk factor for severe COVID-19 is inherited from Neanderthals. (We have noticed that Nature Publications prefer to include H.) By any means, this is an adventurous statement. The team found that severe COVID-19 disease is associated with specific genetic variants in six genes in a 50 k-base-pair-long field of chromosome 3 that are directly inherited from Neanderthals. Similar investigations have also identified a protective Neanderthal haplotype on chromosome (CAR) 12 that reduces the risk of severe covid-9, and a protective field on chromosome 9 that is associated with ABO blood groups.

Not content to rest on their laurels, Pbo and Zeberg have just kicked off one excellent thing. The pair reported recently bioRxiv The preprint server or the other only Neanderthal variant, this time in the promoter field of the DPP4 gene on chr2q24.2, is actually pulling the strings on the covid sensitivity. DPP4 is a widely expressed extracellular diphthedeal peptidase involved in immune function and glucose metabolism. As it happens, the D.P.P. 4 MERS is also a receptor gene for coronavirus. Now we are meeting somewhere.

Yet other researchers have insisted that DPP. 4 is not a SARS-COV-2 receptor, so it is difficult to ignore such coherent findings when therapeutic alternatives are needed. Inhibitors of DPP4, already used clinically for the treatment of diabetes, have an effect on Covid-19 patients. Amid the excitement of ongoing SARS genetic research, we reported on Monday that a handful of immune gene variants, including IFNR2 and TYK2, also control COVID outcomes. Curiously, the study also identified DR4, the sister gene of DD4, living at chr19p13.3, as the main mediator of inflammatory lung injury. DPP9 has the same serine protease activity as DPP4, but differs in that it is not membrane-bound.

The DPP4 gene is not far from the long-degraded residue centromere found nearby in the ChP2q21.3 the q22.1 field. An additional research telomere is also seated in the Q13 band. What are these structures doing here? If one line of the question of what makes us human is pressed for an answer, the best answer is the combination of two small jar chromosomes to make a human chr2. Do Neanderthals have a fused cross 2?

Of course they do. In fact, they have a similar version of the speech gene, FoxP2, which Pebo put on the map in 2002. It seems. Human Foxp2, which differs from the chimpanzee version in two main locations, was famously transformed into the “Kei” family Britain, all of which had a specific disability in the use of the consonant, in a recent COVID risk factor study, using data from the 1000 genomes project. , Then examined with the COVID-19 Host Genetics Initiative to see if the neonarthral had haplotypes for DDP4 associated with disease severity.

The problem with this line of work is that we don’t have enough sequence data to tell us what makes Neanderthals. There are only a few good genomes available from the skeleton ~ 120,000 years old and 50,000,000 years old. These come from Europe and southern Siberia. Such statistical errors make the general public suspicious when their 23 and my scorecards call them 0.98 or 1.67 Neanderthals.

One point that the Kovid epidemic is now successfully running home is that blind medicine will no longer cut it. Blind medicine refers to anything done in the absence of individual patient sequence data. Above, we’ve taken a few cheap shots at paleogenetics and their historical haplotype attribution. This was for good reason, and we have a few more shots to take. When genomics data is provided in terms of reference order, problems can often occur. This is because, in simple terms, there is no such thing as a reference sequence તે even that, is completely arbitrary. Updates and corrections are made from time to time on various reference sequences, but no correct reference sequence will ever occur.

Mers D.P.P. Unlike the 4 receptor, none of the ACE2 receptor variants emerged as a risk factor for severe COVID-19. However, many other genes involved in the SARS-Cavi-2 infection process and life cycle have come to light. For example, four types (rs464397, rs469390, rs2070788 and rs383510) severely affect the expression of TMPRSS2 serine proteases in lung tissue. TMPRS2 – Apocalyptic variants are present at a higher frequency in Europeans and Americans than in Asian populations.

Perhaps a more immediate concern, now that vaccines are being introduced, is the question of who the vaccine can help, and in some cases, who is harmed. The latter probability is usually formulated in light of the now-known phenomenon of antibody-based shelter (ADE). While ADE is taken very seriously for other diseases such as dengue or respiratory syncytial virus, these three bad words are usually simply rejected in the discussion of COVID. However, recent research now suggests that ADE is the very thing in COVID.

In particular, researchers have found that some anti-spike monoclonal antibodies in Covid-19 patients, especially against the N-terminal-domain (NTD) of Spike, have dramatically increased the binding capacity in ACE2, and therefore SARS-Cov. 2 Increased infectivity. . Mutual analysis was used to direct the specific surface area of ​​the NTD. All patients studied had antibodies against this infection-promoting site. Information about spike sequence mutations and ADE risk factors is updated much faster than the time of vaccine development, so it is important for people to get information about the vaccine currently being given about the RNA vaccine. That is, what specific spike sequence is used to produce the vaccine?

Recent reports of new outbreaks of spike mutants have raised more questions. How can a potential vaccine-eving N501Y variant change the game in receptor binding domains or double-NTD-deletion variants? Or how does the new D614G spike variant that provides more efficient replication affect transmissibility and pathogenicity? The answers are getting quicker and furious, and at someone’s risk it will be ignored.

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