A person is infected with malaria by four parasites from the genus of Plasmodium: Plasmodium vivax (pathogen of three-day malaria), P. ovale (pathogen of ovalemalaria), P. malariae (pathogen of four-day malaria) and P. falciparum (pathogen of tropical malaria). A fifth parasite, P. knowlesi (the causative agent of zoonotic malaria), also infects humans, but is considered a parasite of macaques. Of the four parasites, P. falciparum is the most deadly. Female mosquitoes carry it from one person to another. When a mosquito that has just fed on the blood of an infected person bites the second victim, it injects a small portion of saliva with plasmodia, and these migrate to the liver and reproduce there. Then the clones of the second generation enter the bloodstream, there are looking for red blood cells and invade them. Once established in the red blood cells, they multiply again (doubling four times until they become sixteen), and then break out, leaving behind a shell of red blood cells as a discarded husk. Symptoms of this disease include cyclical fever and chills. Sometimes there is a dry cough. In the worst cases (especially in children), P. falciparum causes cerebral malaria. Parasite-infected red blood cells “get stuck” in capillaries throughout the body, causing convulsions, coma, brain damage, and death.
It is possible that for 10,000 years P. falciparum has incessantly cut and forged the human genome in the malarial belt, a vast area covering tropical Africa, the subtropical regions of the Mediterranean, the river valleys of the Levant, and all of South Asia up to Papua New Guinea. Trade contributed to the widespread spread of this parasite. By the time Geoffrey Chaucer wrote his “Canterbury tales” in the fourteenth century, “fever” (as the English called malarial fever) was causing people to fear even in the North, in the British Isles.
At the beginning of the new Millennium, P. falciparum infected between 350 and 500 million people a year. One million patients (roughly equal to the population of Dallas) died from this infectious disease. (The prevalence of the disease and its death rate have since declined by a third.) Most of the victims were children under the age of five who lived in sub-Saharan Africa. In all likelihood, the death rate has always been the same. Possibly caused by P. falciparum death, especially the death of children who had not yet passed on their genes, represented the strongest factor of selective pressure on human genes from a single pathogen. In any case, this is the argument put forward by scientists who seek to explain some unusual and seemingly counterintuitive aspects of protection from P. falciparum.
In 1949, the British scientist John Haldane tried to explain the apparent absurdity of our adaptation to parasites. He argued that because of the need to survive the widespread spread of malaria, the peoples of the Mediterranean region had developed signs that were harmful to themselves. A clear proof of this was a specific anemia-thalassemia. (The word thalassa means “sea”in Greek. People from coastal areas were most affected by this disease.) Haldane believed that this anemia was due to a favorable adaptation to P. falciparum.
Red blood cells contain hemoglobin to transport oxygen through the body. By capturing these cells, P. falciparum destroys hemoglobin. As a result, there are genes that make hemoglobin less attractive to this parasite. However, changing the structure of this extremely important molecule has had inevitable consequences. Children receive two copies of each gene, one from each parent (with the exception of sex – specific genes on the X or Y chromosomes). Thus, although having one variant of the thalassemia gene protects against cerebral malaria, two copies cause anemia and premature death.
Therefore, if each of the two parents has one thalassemia gene, they can have two children like themselves — children protected from cerebral malaria without negative consequences. Excellent. These parents may also have one child without protective genes. Not so great, but acceptable. In addition, these parents may have one child with two copies of the protective gene. This child would have suffered from neonatal hemolytic anemia and would most likely have left this world at an early age. Terribly. However, according to the calculations of natural selection, if two children have innate resistance to a widespread pathogen, the third child is left to fend for themselves, and the fourth is born unhealthy, this still gives a net advantage in total. This is how the sign of thalassemia became widespread.
In 1954, a scientist named Anthony Ellison, who studied malaria in East Africa, came to the same conclusion about another trait, which he called the sickle cell [98]. In carriers of this trait, blood cells had the shape of a Crescent. As in the case of thalassemia, one copy of the gene protected against cerebral malaria, but the presence of two copies doomed the carrier to anemia and early death.
In a more elevated sense, such protection seemed an inelegant solution. However, Haldane believed that when it came to evolution, elegance had no effect on survival. “The fight against diseases, especially infectious diseases, has always been a very important factor in evolution,” he wrote. — Some of its results are very different from the results of the struggle for life in the conventional sense”.
Haldane’s malarial hypothesis is, in fact, proved by fundamental work done in Sardinia. In the 1950s and 1960s, scientists discovered that the frequency of occurrence of variants of the thalassemia gene in Sardinians is directly related to the altitude above sea level at which they live.
The higher the altitude, the rarer these genes are (at higher altitudes, the incidence of malaria is lower). For example, in a high-altitude Tonar, the beta-thalassemia gene is present in 5% of the population. However, in the province of Sassari, located on a low-lying plain in the northwestern quadrant of the island, 25% of the inhabitants have this feature. This corresponds to the historical prevalence of malaria. (Near Sotgiu there is one gene for thalassemia, as well as his wife. In this regard, it became necessary to conduct a genetic examination during pregnancy to make sure that their children will not have hemolytic anemia. They don’t have it.)
However, the height above sea level could not protect many inhabitants of Sardinia. Compared to the neighboring Islands of Sicily and Corsica, the island of Sardinia has a relatively flat terrain — I noticed this when landing. It was late may, and the snow-capped peaks of Corsica contrasted sharply with the verdant hills of Sardinia. Most of the territory of Sardinia is located at an altitude of up to 600 meters above sea level. In other words, P. falciparum probably infected most of the island’s population for thousands of years. And the ubiquity of malaria infection is of great importance for the hypothesis of Sotgiu.
Thalassemia is caused by certain variants of genes, whereas autoimmune diseases are usually much more complex in genetic terms — they involve a whole set of genes. And although scientists have identified some gene variants that increase the likelihood of developing autoimmune diseases, many people with these genes do not develop these diseases, while others who do not have such genes suffer from them. In other words, unlike thalassemia or sickle cell anemia, in the case of autoimmune diseases, genes in no way determine a person’s fate. The environment plays a crucial role. What has changed the environment in Sardinia over the past half century? Here comes to the fore the idea of Sotgiu. Malaria disappeared from the island about 60 years ago. Sotgiu believes that genes that in the past protected the inhabitants of Sardinia from malaria, today, when it is no longer present, cause autoimmune diseases.