Amazing stuff! Natural evolution is very slow and it does not always deliver optimal or good solutions!
"The 14th-century global outbreak of bubonic plague, known as the Black Death, was the deadliest disease outbreak in recorded history, killing up to half of the European, Asian, and African populations. ...
in the genomes of modern humans, including the prevalence of gene variants that may have protected against the causative bacterium Yersinia pestis but which today are associated with an increased risk of developing an autoimmune disease ...
For the study, geneticist[s] ... examined DNA samples from the remains of more than 200 Europeans who lived before, during, or shortly after the 14th-century pandemic, including 42 of its victims. Focusing on immune-related genes, they identified four mutations that appear to have rapidly increased in frequency after the event, suggesting they were selected for and may have improved survival. ...
One of these mutations stood out. It falls in a gene called ERAP2, which is expressed in macrophages and is involved in the cutting and displaying of bacterial proteins on the immune cells’ surfaces. Lab experiments suggested that individuals carrying two copies of the mutation, which yielded a longer RNA transcript than the nonmutated variant, were 40 percent more likely to survive the Black Death, ... that it’s the largest evolutionary advantage for a variant ever identified in people. ...
The downside of this protective ERAP2 variant, however, is that it’s a known risk factor for Crohn’s disease, an autoimmune disorder that affects the gastrointestinal tract. Similarly, the team identified another gene variant that became more common in the human population after the Black Death and is linked to two other autoimmune conditions, rheumatoid arthritis and systemic lupus erythematosus. ...
This study is not the first to show that the adaptive response to the plague may lead to increased risk of autoimmunity. In 2014, for example, a genetic analysis of Europeans and Rroma yielded a similar result, as did a 2021 study of 16th-century German plague victims. ..."
in the genomes of modern humans, including the prevalence of gene variants that may have protected against the causative bacterium Yersinia pestis but which today are associated with an increased risk of developing an autoimmune disease ...
For the study, geneticist[s] ... examined DNA samples from the remains of more than 200 Europeans who lived before, during, or shortly after the 14th-century pandemic, including 42 of its victims. Focusing on immune-related genes, they identified four mutations that appear to have rapidly increased in frequency after the event, suggesting they were selected for and may have improved survival. ...
One of these mutations stood out. It falls in a gene called ERAP2, which is expressed in macrophages and is involved in the cutting and displaying of bacterial proteins on the immune cells’ surfaces. Lab experiments suggested that individuals carrying two copies of the mutation, which yielded a longer RNA transcript than the nonmutated variant, were 40 percent more likely to survive the Black Death, ... that it’s the largest evolutionary advantage for a variant ever identified in people. ...
The downside of this protective ERAP2 variant, however, is that it’s a known risk factor for Crohn’s disease, an autoimmune disorder that affects the gastrointestinal tract. Similarly, the team identified another gene variant that became more common in the human population after the Black Death and is linked to two other autoimmune conditions, rheumatoid arthritis and systemic lupus erythematosus. ...
This study is not the first to show that the adaptive response to the plague may lead to increased risk of autoimmunity. In 2014, for example, a genetic analysis of Europeans and Rroma yielded a similar result, as did a 2021 study of 16th-century German plague victims. ..."
"... One variant affected the expression of a gene called ERAP2. People with the variant produce a full-length version of an RNA molecule that encodes the ERAP2 protein; those who lack it make a shorter version of the RNA.
The ERAP2 protein is made by specialized immune cells called macrophages that engulf and digest bacteria. It is involved in cutting bacterial proteins into pieces, some of which are then displayed on the surface of the macrophage as a signal to other immune cells. ...
speculated that having a full-length, fully functional ERAP2 protein might have improved immune protection during the Black Death. Laboratory studies backed up this idea: macrophages expressing the longer version of ERAP2 were able to keep Yersinia pestis from replicating more effectively than were macrophages expressing the truncated version. ..."
speculated that having a full-length, fully functional ERAP2 protein might have improved immune protection during the Black Death. Laboratory studies backed up this idea: macrophages expressing the longer version of ERAP2 were able to keep Yersinia pestis from replicating more effectively than were macrophages expressing the truncated version. ..."
From the abstract:
"Infectious diseases are among the strongest selective pressures driving human evolution. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis. This pandemic devastated Afro-Eurasia, killing up to 30–50% of the population. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease."
Bubonic plague left lingering scars on the human genome Genes that might have aided survival during the Black Death are now linked to autoimmune disorders.
Fig. 1: East Smithfield mass burial and sample locations, along with date ranges and final sample numbers used for the present study.
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