Evolution doesn’t have purposes, only results. Darwinian natural selection doesn’t shape creatures to be “better” or “higher” in some objective, transcendent sense — it shapes creatures to succeed in the here and now. And what works in one environment or period of time may prove harmful in another. Some scientists say this fact of evolution might help explain the origins of human autoimmune diseases.
They are a bit mysterious, autoimmune diseases, but far from rare. They include multiple sclerosis, rheumatoid arthritis, Type 1 diabetes, lupus, Crohn’s disease, psoriasis and possibly more than 100 others. Some of them cause misery, some discomfort and inconvenience and some can be fatal. What these conditions share is that, for reasons still unclear, a person’s immune cells begin attacking the body’s own tissues and organs instead of just defending against invaders like viruses and bacteria.
Autoimmune diseases are believed to affect about 15 million people in the United States and between 5 and 10 percent of the population of industrialized countries, as well as a smaller percentage in developing countries. And the numbers are rising, probably because of environmental factors, including diet and pollutants, which play a role in setting off these illnesses. But genetic factors likely play a role, too, and that’s where research in recent years has revealed an intriguing pattern.
Autoimmune diseases may arise partly from the action of genes and gene combinations that were valuable at earlier stages of human history but are now disadvantageous. More specifically, scientists have found evidence of natural selection for certain gene variants during the Bronze Age, which began about 5,000 years ago and spanned two millenniums. Those same variants may increase the risk of autoimmune disease in people who carry them today. The term for such opposing effects is “antagonistic pleiotropy,” and a simple way of explaining it is that sometimes a gene helps, and other times it harms.
Why would some gene variants perform a valuable service for ancient humans but a disservice now? One answer, supported by recent studies that draw on genetic sequencing of ancient human DNA and comparisons of those sequences with modern genomes, involves infectious disease.
During those earlier millenniums, humans transitioned from being hunter-gatherers in small, mobile bands to two other ways of living: as farmers and as pastoralists. Farmers were sedentary. Pastoralists turned wild animals into cattle, sheep and goats, and traveled across wide areas so their livestock could graze. Farming brought people into close contact with plants. Pastoralism brought people into close contact with the viruses, bacteria and other infectious agents that wild (and then domesticated) animals carry.
Many of those pathogens crossed into the pastoralists, creating what are now called zoonotic diseases — animal infections that spill over to humans. Survival against such disease threats involved luck and genes. Natural selection culled out the unlucky, leaving populations of survivors who carried lucky gene variants that offered resistance against the infections.
But those protective gene variants of the Bronze Age, it now seems, may have a negative effect in our modern era of good sanitation systems, antibiotics, antiseptics and other infection control measures. By increasing the sensitivity of the immune system to an extreme level, they have become risk factors for autoimmune diseases. That’s the antagonistic pleiotropy hypothesis anyway.
And scientists have found evidence to support it. Researchers at the University of Oxford and their collaborators elsewhere reported a strong correlation between certain gene variants that spread rapidly among European populations around 5,000 years ago and those linked to an elevated chance of having multiple sclerosis today. The variants became more common as migrant pastoralists from the Eurasian steppe began arriving in Europe. Most of those gene variants delivered some protection against certain viral and bacterial infections, or against parasites, helping humans to adapt not just to the pastoral lifestyle, but to increases in population density, which intensified the transmission and circulation of infectious diseases.
Today, according to the researchers, those same gene variants seem to be having an opposite effect. With infectious diseases better controlled and the prevalence of M.S. on the rise, “we again observe a striking correlation with changes in our environment, including lifestyle choices and improved hygiene, which no longer favours the previous genetic architecture,” they wrote. In other words, genes that once protected us may now put us at risk.
Another study from an international team of researchers looked at a more recent historical moment of abrupt demographic change: the Black Death. This 14th-century pandemic of plague (caused by the bacterium Yersinia pestis, which is carried by fleas, which are carried by rats) swept through Europe, the Middle East and northern Africa between 1346 and 1353, killing as much as 30 to 50 percent of the population in those areas.
The researchers scrutinized DNA sequences from the dead in England and Denmark, some buried just before the plague years, some during and some after. One of their sources was East Smithfield, a Black Death mass burial site just east of the Tower of London. There and elsewhere, the researchers found four immunity-related gene variants in the genomes of more people buried after the plague than before or during it, suggesting that those variants had conferred a survival advantage. After a dispute of their mathematical methods by another team, the researchers refocused their assertion on one variant. That variant, evidently adaptive against plague, is now a known risk factor for Crohn’s disease. So it seems that the Black Death, like the transition to pastoralism during the Bronze Age, may have been a selective event that increased the jeopardy of future generations to autoimmune diseases.
Although the Oxford team, in its study of M.S., called this situation a case of outdated “genetic architecture,” there’s another metaphor that makes the same point more vividly. Recall the adage about the failings of military leadership: that generals spend their peacetime preparing to fight the last war, rather than the next one. They cling to obsolete tactics and strategies and weaponry — things that worked well in the past — despite the march of time and the arrival of novelties. This is apparently what evolution has done with the gene variants that many of us carry today. Autoimmune diseases in the 21st century may represent the human immune system’s efforts to fight a war that was once cataclysmic and is now less so against ubiquitous and incurable infectious diseases.
For some people, the miseries of M.S. or lupus or other autoimmune maladies is a cruel misfortune. Others are luckier. For instance, me: I have only my psoriasis (inherited from my father, who inherited it from a lineage of Norwegian country people) as a reminder that my own immune system is ready and eager, too eager, to fight the last war — the war between a Bronze Age herdsman and a virus he picked up from one of his goats.
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