Our ancestors chose to live, but now we are more susceptible to disease

Compared with chimpanzees and other close relatives, we humans seem to be more susceptible to diseases such as cholera and asthma. The susceptibility to this disease may have come from a choice made by our ancestors: the choice was originally designed to save ancient humans, but it also put modern people in a more vulnerable position.

we may have had such a feeling, why is the human body so fragile? There are so many kinds of diseases on us. Moreover, some diseases seem to be specially targeted at human beings, such as typhoid fever, cholera, mumps, pertussis and asthma. These diseases are very difficult for other primates and mammals, and these diseases seem to be special diseases of modern people. The root cause of this strange phenomenon may be a small change made by human ancestors in order to avoid the disease at that time.

after carefully studying the pathogenesis of these diseases, scientists found a common feature: pathogens causing these diseases will use the same way to invade the human body, and sialic acid, a sugar molecule, has become the key to the invasion of pathogens.

sialic acid, a derivative of 9-carbomonosaccharide, is a natural carbohydrate. There are hundreds of millions of sialic acid molecules on the outer surface of our cells, but it is worth noting that sialic acid in humans and apes is not the same.

at a recent symposium on the evolution of infectious diseases at the University of California, San Diego, pathologist Nissi Varki described his research on this phenomenon. After a long-term follow-up with her team, she found out when humans had acquired a molecular weakness that apes don’t have – changing sialic acid.

Varki analyzed the genomes of the extinct Neanderthals and denisovans. The results showed that, 600000 years ago, the immune cells of the ancestors of these three human species, including modern Homo sapiens, had an explosive evolutionary event. Their new research published in pointed out that people in this period produced some gene mutations to resist the use of saliva at that time The pathogen that acids enter the body, Plasmodium.

it is this change that has made our ancestors more resistant to malaria, but it has made modern people carry more “fragile” bodies.

the sialic acid covering the cell surface will contact the top of membrane protein, and the sialic acid molecules will combine to extend. When bacteria or viruses enter the human body, the first thing they recognize is these glycoproteins.

even the new coronavirus is no exception. After it enters the human body, it needs to go through two key steps before infection. The first step is to identify sialic acid and find the suitable binding site; the next step is to combine with high affinity protein to open the channel to enter cells. It has been reported that the new coronavirus needs to bind to sialic acid before binding with ACE2.

Varki pointed out that the reason for this change in human ancestors may be resistance to malaria. After changing the sialic acid molecules, Plasmodium, which can easily infect chimpanzees, cannot bind to the surface of human ancestors’ red blood cells. This change directly gives human ancestors a survival advantage that chimpanzees don’t have, and reduces the risk of death from malaria.

but sialic acid changes are only part of the story. In order to distinguish autologous cells from foreign invaders, the immune system has sialic acid binding immunoglobulin like lectin. When siglec recognizes sialic acid molecules from other pathogens, it activates an immune response to kill the pathogen. Even if the sialic acid molecules in the cells in your body are damaged, they will also send out immune signals to let the immune cells clean up the damaged cells.

this has also been confirmed in the study: some key mutations have also occurred in the siglec gene of Neanderthals and denisovans, but not in apes. In addition, the hot spot of gene evolution at that time only appeared in siglec gene, while the side gene did not change, which also showed that these changes were conducive to the survival of human population at that time.

although it is only a small change, it is a big event for the immune system. With Neu5Ac, the risk of human beings living in malaria prone areas is significantly reduced.

this is a good thing in itself, but with the evolution process, in addition to immune cells expressing mutated Siglecs, other tissues of the human body will also begin to express these mutated Siglecs, which is also the inevitable result of competition with diseases, keeping all parts of the body on high alert.

this means that the human ancestors may have paid a lot for the benefits. When this mutation is enriched in a certain group of human ancestors, it will cause fertility disorders among different human populations.

for example, when a woman carrying only Neu5Ac is mated with a man who still expresses Neu5Gc, her body can recognize that the sialic acid molecule of sperm is different from that of herself, thus rejecting male sperm. This kind of fertility disorder may also directly lead to the segregation of previous genera for 2 million years.

in view of the fact that Neanderthals and denisovans have this mutation, but chimpanzees do not, the study suggests that this immune evolutionary event occurred before Homo sapiens separated from their close relatives, and it is likely that the event occurred in Homo erectus, the common ancestor of the three. Novel coronavirus pneumonia is also a risk factor for

. The Siglec study also suggests that the immune system is more likely to develop an immune response to itself because of the longer lasting vigilance of the immune system.

human ancestors avoided the invasion of Plasmodium by changing sialic acid molecules. However, they did not expect to leave a more extensive invasion of pathogens to their offspring. Vibrio cholerae, smallpox virus and influenza virus all infected cells through this new sialic acid molecule, and apes that did not make changes were hardly affected by the above pathogens.

according to Rita gerardy schahn, a biologist at the Hanover Medical School in Germany, it also shows that decisions made by natural selection do not necessarily represent the best solution, because the so-called best plan is always changing. “In the short term, the beneficial choice may be a wrong decision for future individuals.” Rita said. And we have to pay for the decision made by our ancestors.