The history of people's discovery can be traced back to the discovery of tobacco leaves in 1892, but the actual history is much longer than human history. Widely distributed in nature, whether animals, plants, fungi, bacteria and so on. , all have their corresponding.
With the deepening of the research on new coronary pneumonia, people are increasingly asking such questions: how do humans and other animals cope with various infections in the long-term evolution process? Because humans belong to primates, let's first look at the situation of primates (Figure 1).
Fig. 1: A pathogen map (the map comes from collaterals); B primate map (picture from the network); C distribution map of primates and their known pathogens, with blue representing low abundance and red representing high abundance (the map was revised by reference [1]).
Primates are mainly distributed in tropical and tropical regions, which are also rich in pathogens. Therefore, the evolutionary history of primates has always been accompanied by "mutual love and mutual resistance."
"Century Competition" between Host and Pathogen
In addition to its small size, it is not easy to be detected, and it has a more surprising "skill": it will continue to evolve in the offensive and defensive warfare that coexists with its host for a long time. Long-term coexistence with the host involves an evolutionary concept: "co-evolution". "Co-evolution" refers to the adaptive co-evolution of two interacting species in the process of evolution. For example, it needs to bind to the receptor protein in the host, thus infecting the host cell. Just as COVID-19 invades cells by binding to human ACE2 protein. The "evolutionary strategy" of host receptor protein is to avoid binding by changing amino acid sequence; On the contrary, our "evolutionary strategy" is to ensure binding by changing the amino acid sequence of self-binding proteins. This is an "arms race" in the molecular world (Figure 2).
Figure 2. The "arms race" between the host and the receptor protein, the arrow indicates that it can be infected, and the cross indicates that it cannot be infected (the figure is modified by reference [2]).
Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered in 20 12. It was identified that the main host receptor of MERS-CoV was DPP4 protein. In the "battle" with MERS-CoV, different species show different characteristics. There are five key amino acids in the domain of DPP4 protein, which determine the host's anti-infection ability to MERS-CoV. Compared with humans, hamster's DPP4 domain has five amino acid position mutations, which makes MERS-CoV lose its ability to bind to hamster's DPP4, so hamster "loses" its strong anti-infection ability to MERS-CoV. However, in primates, the positions of these five amino acids are different from those of hamsters, and MERS-CoV can bind to the DPP4 domain of primates (including humans), so the anti-infection ability of primates is poor (Figure 3).
Figure 3. MERS-CoV and DPP4 proteins (figure revised according to reference [3])
Man and the "Arms Race" of Evolution
Frequent "conflicts" between the host and the host led to an "arms race" between them. On the one hand, the host receptor protein constantly mutates to improve the resistance to, on the other hand, it tries to "make" changes to achieve successful infection to the host, so there will be periodic adaptation and anti-adaptation between hosts. This phenomenon is often referred to as the "red queen" scene. This somewhat "literary" statement is the English fairy tale Alice in Wonderland. The red queen replied to Alice, "In this country, you have to keep running to keep you in place." L van Valen, an evolutionary biologist at the University of Chicago in the United States, put forward this philosophical hypothesis in 1973, which appropriately described the co-evolution phenomenon in nature. This rule also has a certain practical effect. If the host's receptor proteins find detectable adaptive evolution, it means that they may have been or are being infected. By studying the adaptive evolution of bat ACE2 protein, researchers predicted that bat might be one of the hosts of SARS, and this prediction was also proved by later experimental research.
Which host proteins will you fall in love with?
The quantity of protein is very small, so it is unrealistic to attack the host randomly. Experiments show that the interaction with human protein is achieved through targeted attacks (Figure 4). So what are the characteristics of the target? The researchers found that the receptor protein used for "precise attack" mainly has the following characteristics: 1. The evolution speed is slow (slow); 2. Wide expression range (multiple); 3. Lack of stable three-dimensional structure (chaos). These characteristics will increase the possibility of combining them. This is also well understood: protein, which has a slow evolution speed, is relatively conservative, and is generally an important protein, which participates in many pathways in the body and exists in a large number of cells with flexible conformation. After invading the host, protein, which is widely expressed (ubiquitous) and slow in mutation (slow in operation), is easily harassed, so it is easy to be targeted.
Figure 4. Protein group and human protein group (figure revised according to reference [4])
The defense line of host resistance
So in the face of invasion, the host can only do nothing? The answer is of course "no"!
After invading the host, there is a mechanism of detection and confrontation in the host. For example, Toll-like receptors (TLR) are a family of proteins that recognize pathogen receptors. Four members of mammalian TLR protein family are related to nucleic acid recognition: TLR3, TLR7, TLR8 and TLR9 (Figure 5).
Figure 5. TLR receptor protein family (figure revised according to reference [5])
Crimean-Congo fever is an acute disease caused by members of Buniaceae, which has a high incidence in humans. The disease is usually transmitted to humans through tick bites. TLR8 and TLR9 in human body are helpful to understand this disease and cause corresponding immune response in the body. The researchers found that when Valine (val) at position 1 in the amino acid sequence of TLR8 was mutated into Methionine (met), individuals were less likely to be infected with Crimean-Congo fever.
But the host will also "attend to one thing and lose another"
In the human genome, the host-restricted natural immune molecule TRIM5α is one of the key factors to inhibit replication. The inhibitory effect of TRIM5α on specific drugs is usually determined by its amino acid sequence. PtERV (an ancient endogenous reverse transcription) and HIV- 1 (human immunodeficiency) are two kinds. The researchers found that the amino acid at the third position in the specific region of TRIM5α B30.2 domain was different in different primates, which led to different primates' inhibitory abilities on PtERV and HIV- 1. In humans and chimpanzees, the third amino acid in B30.2 domain is arginine R, which is different from glutamine Q in gorillas. TRIM5α of human and chimpanzee can effectively inhibit the replication of PtERV, but it can't effectively inhibit the replication of HIV. On the contrary, TRIM5α of gorillas can inhibit HIV- 1 more than PtERV (Figure 6).
Figure 6. Amino acid differences and different inhibitory effects of TRIM5α molecules in primates (figure modified by reference [6]).
Interestingly, everything is in balance. When nature opens a "window" for the host, it will inevitably close a "door" for the host. There is also a "balance" between the inhibitory effects of TRIM5α inhibitors on PtERV and HIV- 1 in primates, with one inhibiting ability enhanced and sometimes the other inhibiting ability decreased.
In the process of long-term coexistence with the host, both sides have established a set of evolutionary mechanisms of "attack" and "defense". Objectively speaking, it is also a life form in nature, and their evolution also follows the laws of nature. These objective laws are gradually and deeply revealed through systematic scientific research. What we need to do is to respect and reveal the objective laws of nature. This will definitely help mankind to better control and "overcome"!
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: Qian, Yang, Liu Zhijun
: China Institute of Zoology
The above is about why people love each other, and it is about sharing animals. I read that everyone together will get sick. I hope this will help everyone!