Homo Sapiens and Neandertals: The COVID-19 Connection

Frederick L. Coolidge¹ and Apeksha Srivastava²

1 - Professor, University of Colorado, Colorado Springs

2 - PhD Candidate, Indian Institute of Technology Gandhinagar

Neandertals are our genetic “cousins” with whom we shared a common ancestor about 600,000 years ago. Over the past 100,000 years, they began to decline in numbers and went extinct about 30,000 years ago. The reason for their extinction remains one of the greatest mysteries in anthropology. Interestingly, genetic studies have suggested that there was limited interbreeding between Homo sapiens and Neandertals since about 80,000 years ago. This exchange of genes led to about 1% to 4% of the Neandertal genes to be present in Asian and European populations, and up to 6% in modern-day Melanesians. Recently, the presence of their genes has also been found in some people of African origin.

Fascinatingly, two recent genetic studies have shown that Neandertal genes may “either be a blessing or a curse” with respect to a human’s response to the COVID-19 virus, i.e., these genes can either increase the risk of severe COVID-19 or offer protection against it.

In the first study, Zeberg and Pääbo (2020) identified a gene cluster on chromosome 3 in humans as a major risk factor for severe symptoms and respiratory failure in COVID-19. Chromosome 3 is the third largest of the 23 human pairs of chromosomes, and contains about 200,000 base pairs (guanine-cytosine, adenine-thymine), which are the building blocks of DNA. Chromosome 3 accounts for around 7% of the total human genetic material.

The specific gene cluster they identified on chromosome 3 was shown to be inherited from Neandertals, and it is present in about 50% of the South Asian, 16% of the European, and 9% of American populations. Zeberg and Pääbo found that this gene cluster was almost identical to a 50,000-year-old Neandertal found in Croatia. Thus, it may be a significant contributor to severe COVID-19 in some populations of the world as compared to others.

It is well known that the symptoms of the COVID-19 virus vary tremendously, with some people having no symptoms, some experiencing mild to moderate symptoms, and some who quickly develop severe breathing problems. Further, about 2% of COVID-19 cases result in death. Initially, it was thought that only elderly people were susceptible to dying from the virus, but of course, it was recognized that people of any age could die from it. Other risk factors were identified such as obesity, diabetes, and heart and lung conditions. Another purported risk factor was blood type, although it remains contentious. However, these risk factors still do not account completely for why some people have no or mild symptoms and some die. Because most of these comorbid health conditions have a genetic component, it is now clear that there may be basic genetic risk factors, such as the ones proposed by Zeberg and Pääbo.

In a follow-up study by Zeberg and Pääbo (2021), they found a gene cluster on chromosome 12 that significantly reduced the risk of severe COVID-19 symptoms by about 22%, which was also inherited from Neandertals. Chromosome 12 contains 134,000 base pairs and accounts for about 4.5% of the total human DNA. Interestingly, it also contains some of the critically important homeobox (HOX) genes, which control embryonic development.

The gene cluster on chromosome 12 is known to “initiate attacks on the virus” by regulating the activity of enzymes that break down the viral genetic system. Although both the Homo sapiens and Neandertal gene clusters on chromosome 12 can attack the virus, the Neandertal variant seems to accomplish this function more efficiently. Again, this variant was almost identical to that found in the 50,000-year-old Croatian Neandertal and also in other Neandertals dating back to 120,000 years.

In summary, it is striking that these two gene clusters that we inherited from Neandertals can affect the COVID-19 outcomes in totally opposite directions—one increasing the risk of severe coronavirus disease while the other protects us from it. It is provocative to think that our Neandertal genes, especially in the case of the present pandemic, can be villainous or heroic. It is also provocative to think that even though our Neandertal cousins are extinct, they are still significantly influencing our reactions to this disease. Further, there is a strong possibility that Neandertal genes in modern-day humans could play key roles in other health conditions and in our response to novel organisms and viruses in the future.

For further reading about Neandertals, see How to Think Like a Neandertal, authored by F. L Coolidge and T. Wynn and published by Oxford University Press (2013).