Creationism in Crisis - How Our Immune Systems Have Evolved Over the Last 10,000 Years

Creationism in Crisis

How Our Immune Systems Have Evolved Over the Last 10,000 Years

Using paleogenomics to elucidate 10,000 years of immune system evolution | Institut Pasteur

Explanatory diagram.

© Gaspard Kerner, Institut Pasteur

By analysing the genomes of more than 2,800 individuals who lived in Europe over the last 10,000 years, scientists at the Institut Pasteur, Université Paris Cité, the CNRS and the Collège de France, in collaboration with the Imagine Institute and The Rockefeller University, USA, have traced how the European human immune system has evolved over that period. The increase in frequency of most of the mutations that are advantageous in defending against pathogens were dated to after the Bronze Age, 4,500 years ago.

The scientists also observed that most of the mutations conferring a higher risk of developing inflammatory disorders have become more frequent over the past 10,000 years, suggesting that there is an evolutionary trade-off between greater immunity and greater risk of auto-immune, inflammatory disorders.

This trade-off, is, of course, something that we would not expect to see if the immune system had been improved by an intelligent designer, unless the designer malevolently intended us to suffer from auto-immune conditions.

The evolutionary explanation for this is simply that most of the benefit of a strong immune system manifests in childhood and early adulthood, before the individual has been exposed to environmental pathogens and built up a library of antibodies, and before they have had chance to produce offspring, when selection pressures are thus higher, whereas most of the detriment of auto-immune inflammatory conditions tends to occur in later life, after the individual has reproduced, when the selection pressure is thus much lower.

The research has just been published open access in the journal Cell Genomics.

The research and its significance are explained in a news release from the Institut Pasteur:

In the 1950s, the geneticist J.B.S. Haldane attributed the maintenance or persistence of the mutation responsible for anomalies in red blood cells commonly observed in Africa to the protection these anomalies provided against malaria, an endemic infection that claims millions of lives. This theory suggested that pathogens are among the strongest selective pressures faced by humans. Several population genetics studies subsequently confirmed the theory. But major questions remained, especially regarding the specific epochs during which the selective pressures exerted by pathogens on human populations were strongest and their impact on the present-day risk of developing inflammatory or autoimmune disorders.

To address these questions, scientists from the Institut Pasteur, Université Paris Cité, the CNRS and the Collège de France, in collaboration with the Imagine Institute and The Rockefeller University (United States), adopted an approach based on paleogenomics. This discipline, which studies the DNA from fossil remains, has led to major discoveries about the history and evolution of humans and human diseases, as illustrated by the decision to award the 2022 Nobel Prize in Physiology or Medicine to the paleogeneticist Svante Pääbo. In the study led by the Institut Pasteur, published on January 13 in the journal Cell Genomics, the scientists analyzed the variability of the genomes of more than 2,800 individuals who lived in Europe over the past ten millennia – a period covering the Neolithic, the Bronze Age, the Iron Age, the Middle Ages and the present.

By reconstituting the evolution over time of hundreds of thousands of genetic mutations, the scientists initially identified mutations that rapidly increased in frequency in Europe, indicating that they were advantageous. These mutations that evolved under "positive" natural selection are mainly located in 89 genes enriched in functions relating to the innate immune response, including especially the OAS genes – which are responsible for antiviral activity – and the gene responsible for the ABO blood group system. Surprisingly, most of these positive selection events, which demonstrate a genetic adaptation to the pathogenic environment, began recently, from the start of the Bronze Age, around 4,500 years ago. The scientists explain this "acceleration" in adaptation by the growth in the human population during this period and/or by strong selective pressures exerted by pathogens in the Bronze Age, probably linked to the spread of severe infectious diseases such as plague.

At the same time, the scientists also looked at the opposite situation, in other words, mutations whose frequency fell significantly over the past ten millennia. These mutations are probably subject to "negative" selection because they increase the risk of disease. They noted that once again, these selection events mainly began in the Bronze Age. Many of these disadvantageous mutations were also located in genes associated with the innate immune response, such as TYK2, LPB, TLR3 and IL23R, and have been confirmed in experimental research to have a deleterious effect in terms of infectious disease risk. The results emphasize the value of adopting an evolutionary approach in research on genetic susceptibility to infectious diseases.

These results suggest that the risk of inflammatory disorders has increased in Europeans since the Neolithic period because of a positive selection of mutations improving resistance to infectious diseases.

Lluis Quintana-Murci, senior author
Head of the Human Evolutionary Genetics Unit
Institut Pasteur/CNRS Evolutionary Genomics
Modeling and Health Unit
Université Paris Cité)

Finally, the scientists explored the theory that the selection exerted by pathogens in the past gave an advantage to alleles conferring resistance to infectious diseases, but that in turn these alleles have increased the present-day risk of autoimmune or inflammatory disorders. They investigated the few thousand mutations known to increase susceptibility firstly to tuberculosis, hepatitis, HIV or COVID-19, and secondly to rheumatoid arthritis, systemic lupus erythematosus or inflammatory bowel disease. By looking at the evolution of these mutations over time, they observed that those associated with an increased risk of inflammatory disorders – including Crohn's disease – became more frequent over the past 10,000 years, while the frequency of those associated with a risk of developing infectious diseases decreased.

The results of the study, which harnessed the huge potential of paleogenomics, show that natural selection has targeted human immunity genes over the past ten millennia in Europe, especially since the start of the Bronze Age, and contributed to present-day disparities in terms of the risk of infectious and inflammatory diseases.

From the published paper:

Graphic Abstract

Highlights

• Ancient genomics studies allow detection of the extent of natural selection over time
• Genetic adaptation in Europe has mainly occurred after the start of the Bronze Age
• Immunity genes have been strongly affected by both positive and negative selection
• Resistance to infection has increased inflammatory disease risk in recent millennia

Summary

Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day inflammatory disease risk. Here, we use an ancestry-aware approximate Bayesian computation framework to estimate the nature, strength, and time of onset of selection acting on 2,879 ancient and modern European genomes from the last 10,000 years. We found that the bulk of genetic adaptation occurred after the start of the Bronze Age, &tl;4,500 years ago, and was enriched in genes relating to host-pathogen interactions. Furthermore, we detected directional selection acting on specific leukocytic lineages and experimentally demonstrated that the strongest negatively selected candidate variant in immunity genes, lipopolysaccharide-binding protein (LBP) D283G, is hypomorphic. Finally, our analyses suggest that the risk of inflammatory disorders has increased in post-Neolithic Europeans, possibly because of antagonistic pleiotropy following genetic adaptation to pathogens.

Kerner, Gaspard; Neehus, Anna-Lena; Philippot, Quentin; Bohlen, Jonathan; Rinchai, Darawan; Kerrouche, Nacim; Puel, Anne; Zhang, Shen-Ying; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent; Patin, Etienne; Laval, Guillaume; Quintana-Murci, Lluis
Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe
Cell Genomics 2023); 100248. DOI: 10.1016/j.xgen.2022.100248

Copyright: © 2022 The authors.
Published by Elsevier, Open access.
Reprinted under a Creative Commons Attribution – NonCommercial – NoDerivs license (CC BY-NC-ND 4.0)

It should be obvious to any objective person that it would not have been beyond the wit of an intelligent designer to come up with an immune system that doesn't run the risk of producing autoimmune inflammatory conditions the more it is exposed to pathogens, so the notion that this system is the work of just such a designer can be disregarded.

It should also be obvious to anyone reading this paper that the scientists who wrote it were under no doubt that what they observed is the result of an evolutionary process. Indeed, they consider the TOE to be the foundation of their science and the only scientifically valid way to interpret the observations.

Taken together, these two facts alone should tell any objective reader that it is Creationism that is a notion in crisis, not Evolution, which continues to be the unchallenged fundamental theory of biology. Anyone claiming otherwise is simply lying.

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