After leaving Africa some 45,000 years ago (probably even earlier), modern humans arrived in Australia and 40,000 years ago in Europe. There they found meadows in which trees grew in places and were inhabited by mastodons, woolly rhinos, horses, cave bears, mammoths, saber-toothed lions and bison. For a Millennium, the climate was extremely unstable and was characterized by a rapid retreat and the onset of huge ice sheets from the North. However, there was a General trend towards the great cold snap, which peaked 20,000 years ago when much of the British Isles and Scandinavia were covered in ice and what is now known as the English channel turned into an icy steppe.
For tens of thousands of years before the onset of this peak of cold weather, ancient Europeans had good health. Judging by the skeletons left after them, they were tall and broad-boned . They had a lot of food and a lot of exercise. Compared with later periods, they suffered almost no infectious diseases. It is believed that the average height of men was about 174 centimeters, and women-about 163 centimeters, which is approximately in line with modern indicators. The oval cross-section of the femur bone (a sign that the anterior and posterior thigh muscle groups pulled this bone back and forth throughout life) suggests that they walked a lot. In more sedentary populations, such as farmers and especially modern office workers, the femur has a circular cross-section.
As climatic conditions changed, so did the bones of ancient Europeans. About 20,000 years ago, glaciers pushed people South. Europeans of the late Paleolithic lost almost ten centimeters of height: men at that time had a height of about 165 centimeters, and women a little more than 152 centimeters. The bones of the legs became less strong, and their cross-section from oval to round. The phalanges of the toes began to atrophy about 40,000 years ago in East Asia and 26,000 years ago in Europe — this indicated that at that time shoes first became widespread.
At least since the 1980s, archaeologists have blamed the deterioration of health (which has been noted since humans began farming and herding) on agriculture, with its less protein-rich and more varied diet, as well as increased morbidity associated with sedentary lifestyles. These arguments were partly based on research conducted on both American continents, where members of some communities who began to grow corn did indeed have poorer health than their hunter-gatherer ancestors. However, additional research has complicated this picture. In some cases, farmers were healthier than their direct ancestors. More important for our purposes is the fact that in the Western part of Eurasia, human health began to deteriorate thousands of years before the birth of agriculture.
By the end of the Paleolithic era, large animals that were easy to hunt also became rarer, and communities had to settle for less attractive food, such as shellfish, and hares in the Middle East . Communities have become less mobile, and diseases such as porotic hyperostosis (the appearance of many small holes in the bone) have become more common. This disease, due to anemia, may indicate a low iron content in food, more diseases, an increase in parasitic load — or all of this at once.
Anthropologist Brigitte Holt will relate these changes to the increasing concentration of population and a more sedentary lifestyle due to the absorption of land glaciers and increasing human population. Perhaps for the first time in the history of evolution, we began to feel the negative effects of success: crowding and lack of resources.
Geneticists find evidence of an increase in the number of different tribes, especially in regions with warm climates, starting even from an earlier period. About 41,000 years ago on the sub-Saharan African continent, the number of members of hunter-gatherer tribes such as the San and bayaka tripled . The number of tribes proto-axe and mandenka increased seven times 31 000 years ago . And 22,000 years ago, during the glacial maximum, the population of northwestern Africa increased eleven-fold.
Why is it important? As the crowding of the human population contributed to the increase in the number of epidemics, it began to affect the genes of our immune system, which led to consequences in terms of exposure to inflammatory diseases. For example, between 100,000 and 500,000 years ago, a spontaneous mutation inactivated the caspase-12 gene, which helps identify bacteria that cause infectious diseases. The presence of the original, unmutated version meant a quick and decisive reaction to bacterial pathogens. However, the mutated version provided a slower, sluggish immune response. At the time of its emergence (perhaps hundreds of thousands of years ago), the inactive version of this gene did not attract the attention of natural selection. However, between 10,000 and 60,000 years ago, something changed in the overall picture of diseases. Carriers of the unactivated version began to leave behind more descendants than those who did not have this version of the gene .
Why should non-functional gene got the advantage? As it turned out, the inactivated gene protects against sepsis. The severity of this disease depends in part on the bacterium-the causative agent of infectious diseases and on the human immune response. A crushing retaliation can lead to increased blood clotting, organ failure, and even death. Nowadays, a third of people affected by sepsis die, but people with two copies of this mutant gene are eight times less likely to die from sepsis than those who do not. Therefore, our answer is this: this gene has spread because people began to face a large number of pathogens that cause sepsis. Those who had an active hereditary version of this gene had an increased predisposition to sepsis.
Other genes also responded to the change in disease patterns, albeit with different outcomes. For example, a nonfunctional variant of the CARD8 gene also began to spread . This gene prevents the formation of an inflammatory cascade. In this case, the non-functional version of the gene is like a broken switch: the bulb remains on at all times and inflammatory processes continue to develop. Thus, in contrast to the mutation of the caspase-12 gene, the” zero ” variant of the CARD8 gene increased the human ability to fight microorganisms. However, such a “broken switch” has a disadvantage: it causes a tendency to inflammatory diseases such as rheumatoid arthritis.
Like humans, other animals that group together and are exposed to many pathogens also tend to lose the functionality of this gene (which means they have a prolonged inflammatory response). Mice, cows and horses have a nonfunctional version of the gene. However, cats and dogs maintained working gene. Chimpanzees, gorillas, and orangutans (primates living in relatively small groups) also retain a functional version of this gene. On the contrary, rhesus macaques that group together in groups of hundreds of individuals are likely to lose it.
In our case, the prevalence of the non-functional version is directly proportional to how long our ancestors were engaged in cattle breeding and agriculture. Very few hunters and gatherers (10% of the San and only 4% of the Pima Indians) have a “broken switch”version. In people who started farming and cattle breeding relatively recently (over the past four thousand years), this gene is much more common.
The variants of these two genes (one turns on the immune response and the other turns it off) embody an immune dilemma: an irresistible force (the hereditary caspase-12 gene) seems to be the obvious preferred choice. However, if your reaction is reduced to the use of extreme measures every day, you will inevitably face a complete defeat. On the other hand, if you are regularly attacked, you need some form of permanent response (the”broken switch” of the non-functional gene CARD8), but in this case you are at risk of inflammatory disease.
The immune system has always had to bypass such pitfalls, on the one hand, creating opportunities for self — destruction, and on the other-being exposed to the destructive effects of opportunistic microorganisms. Awareness of the dangers inherent in this balancing act is essential to understanding our genetic predisposition to autoimmune diseases today. In all likelihood, gene variants now associated with autoimmune and allergic diseases have helped to counteract pathogens in the past. And almost certainly they didn’t cause so much trouble.