Did a poor immune system contribute to Neanderthal extinction?

By: Kaili Jackson, Yash Malai, Nina Parziale, and Nick Perry (Stonehill College, BIO323 Evolution, Spring 2018)

Despite the many great technological and scientific advances that have defined the 21st century thus far, there are many important questions that remain unanswered. Among them is the ultimate reason that Neanderthals went extinct while humans were capable of further survival. There are several theories as to why this occurred, and scientists continue to debate which factors may have contributed to Neanderthal extinction to the greatest extent. Some examples of suggested theories include the possibility that climatic fluctuations may have had a negative impact on Neanderthals; the hypothesis that modern humans’ shorter gestation period allowed for more rapid population growth; and the proposition that the intelligence and language capabilities of modern humans were superior to Neanderthals, allowing them to develop better hunting strategies such as the domestication of dogs to aid them during large animal hunts. Another potential theory, which the article An evolutionary medicine perspective on Neandertal extinction presents research on, is that viral disease transmission from modern humans may have contributed to the ultimate extinction of Neanderthals. This research was led by Alexis Sullivan from the Department of Biology at Pennsylvania State University. This theory is known as the differential pathogen resistance model.

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It has been confirmed that beginning at least 45,000 years ago, interbreeding and thus direct contact of humans and Neanderthals occurred in Eurasia. Therefore, it is possible that transfer of infectious diseases between the two species may have occurred throughout this time. Upon further analysis of the Neanderthal nuclear genome and that of the Eurasian modern humans, it was revealed that the genetic diversity of the Neanderthal genome was considerably lower. This lack of diversity may have left the immune systems of Neanderthals more susceptible to pathogens. Additionally, it was observed that the Neanderthal genome contained a higher proportion of predicted damaging amino acid alterations than benign amino acid alterations when compared to humans, which reduced the Neanderthals’ ability to decrease the frequency of deleterious variants. With this known, scientists could then assess the accuracy of the differential pathogen resistance model by researching the levels of genetic diversity in genes for which increased genetic variation is suggested to improve pathogen defense among Neanderthals and African, European, and Asian modern humans.

For this experiment, the single-nucleotide polymorphism (SNP) genotypes for 13 individuals comprised the dataset. These individuals were three modern humans of African descent, three modern humans of European descent, three modern humans of Asian descent, three Neanderthal individuals, and one individual from the archaic hominin Denisovan population. Patterns of Neanderthal-human genetic diversity were evaluated within three subsets of genes for which diversity is thought to play a role in the immune system’s response to pathogens. The first set comprised 73 innate immune-receptor, signaling-adaptor-molecule, and complement pathways. The second set comprised 164 genes encoding for virus-interacting proteins that have known antiviral activity or broader immune system roles. The third set comprised 12 MHC genes, which are critical immune system loci. In addition to these data, patterns of Neanderthal-human genetic diversity were evaluated within a set of genes that are consistent with high levels of genetic diversity among apes. This was done to provide a dataset that was unbiased, as most studies of balancing selection in mammals have been based at least in part on human population genomic data.

The results showed that Neanderthal and human nonsynonymous genetic diversity was similar between the genome-wide and immune system gene sets, with fewer nonsynonymous SNPs in Neanderthals for both cases. Though this difference exists, it can not be deemed statistically significant based on Fisher’s Exact Tests and is not significantly lower than expected by chance. For the virus-interacting protein genes, there were also fewer Neanderthal nonsynonymous SNPs when compared to humans. However, when the 12 MHC genes were observed, it was actually found that there was a greater number of total nonsynonymous SNPs for Neanderthals than for any of the three human populations. When the pattern of Neanderthal versus modern human nonsynonymous genetic diversity for the top 1% ape diversity gene set was studied, it appeared to be more similar to the observed immune system genes than the MHC genes.

Based on these results, it was concluded that the differential pathogen resistance model was not supported in full. Although Neanderthal nonsynonymous genetic diversity was lower at immune system, virus-interacting protein, and ape high-diversity gene loci when compared to humans, Neanderthal MHC diversity was similar or even higher than humans in many aspects. Therefore, it may be possible that the low level of diversity at three out of the four gene sets studied may have resulted in decreased pathogen resistance, but it cannot yet be determined if the higher level of diversity at the 12 MHC loci outweighed the other loci in terms of its effect on the level of pathogen resistance in Neanderthals in comparison to humans. This study may not have proved without a doubt that a lower level of pathogen resistance played a significant role in the extinction of Neanderthals, but it also cannot be ruled out. Further research must be done to explore the feasibility of the differential pathogen resistance model to a greater extent.

Link to article (behind a paywall): https://www.sciencedirect.com/science/article/pii/S0047248417301148

Citation: Sullivan, A.P., M. de Manuel, T. Marques-Bonet, & G.H. Perry. 2017. An evolutionary medicine perspective on Neandertal extinction. Journal of Human Evolution 108: 62–71.

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