Mitonuclear incompatibility
Selection pressure forces the nuclear genome to remember its roots
Maxim Abdulaev, "The Attic"
When mixing different populations, the problem of incompatibility of the genomes of the nucleus and mitochondria appears. To prevent this from happening, the nuclear genome must "adjust" to the mitochondrial gene.
Scientists have studied the genome of representatives of three different races and their mestizos and found that if the geographical origin of mitochondria (inherited from one of the parents, usually mothers) differs from the origin of the cells in which they live, then the functions of mitochondria are difficult. Nevertheless, under the pressure of selection, the nuclear genome in the populations of African Americans and Puerto Ricans adapts to the mitochondrial one and thus "preserves the memory" of the land of their distant ancestors.
Mitochondria most likely originate from some ancient organisms that entered into symbiosis with eukaryotes at the beginning of the development of life on Earth. The different origins of mitochondria and human cells have led to the fact that these organelles have their own genome. The genome is small, it carries only 37 genes, some of which encode proteins necessary for the most important business of mitochondria – cellular respiration, the main source of energy of the human body.
The mitochondrial genome does not carry all the genes necessary for the operation of this organelle. Even more than 1000 genes that she needs are located in the cell nucleus. For mitochondria to function normally, the nuclear genome must be compatible with its own. If the nuclear and mitochondrial genomes are in dissonance, then the proteins encoded by nuclear genes do not cooperate well with mitochondrial proteins and their carriers begin to have problems. The active centers of "nuclear" and "mitochondrial" enzymes, for example, may be at the wrong distance from each other in the respiratory chain, it will begin to malfunction, excess electrons will accumulate in it, and then superoxide radicals – reactive oxygen species that are very harmful to the cell.
Mitonuclear incompatibility (MN), that is, just such a situation, can have important consequences. For example, it may be one of the reasons for the appearance of non-interbreeding between related species, thus "separating" populations that have lived in isolation from each other for a long time. The consequences of MN in humans are still poorly understood.
Scientists from Pennsylvania State University conducted a study (Zaidi & Makova, Investigating mitonuclear interactions in human admixed populations) using data from the 1000 Genomes project, during which the genome of over a thousand people from different parts of the planet was decoded. The authors took data from six groups in which the mixing of populations is particularly noticeable – these are African Americans from the southwest of the United States, Africans from Barbados, Colombians from Medellin, Mexicans from Los Angeles, Peruvians from Lima and Puerto Ricans from Puerto Rico. In all these communities, the genomes of Europeans, Africans and Native Americans (Indians) were mixed in different combinations. Mixed populations were chosen because, according to the hypothesis of scientists, mitonucleal incompatibility would most likely be noticeable in them. For comparison, scientists took data on the genomes of white Utah residents, representatives of the Yoruba tribe from Nigeria and the Maya, Aymara, Quechua and Nahua peoples from Central and South America.
After examining the genes of the studied groups, the scientists found a negative effect of mitonuclear incompatibility: the greater the incompatibility between nuclear and mitochondrial genes, the fewer copies of mitochondrial DNA were synthesized in the cells of the studied people. Scientists believe that this is due to the fact that proteins that participate in the replication of mitochondrial DNA are formed by nuclear DNA, and if there are too many differences, they may not recognize the point of origin of replication Mitochondrial DNA. Thus, replication goes badly and the number of copies of mitochondrial DNA decreases. This is due to unpleasant things – with an increased risk of diabetes, Parkinson's disease, male infertility, depression and cancer, as studies from previous years have shown.
The second observation of scientists is related to how much the part of nuclear DNA encoding what mitochondria need differs from the rest of nuclear DNA. It turned out that it differs most from the rest of the nuclear genome and is more similar to the ancestral one in two groups – African Americans from the United States and Puerto Ricans. They have it most similar to the DNA of Africans and Indians, respectively.
The Mexicans had exactly the opposite: the sections of nuclear DNA useful for mitochondria turned out to be more similar to European ones. Perhaps this is due to the fact that, compared with the other five groups, the data on which the scientists used in their study, the Mexican group had the most people with mitochondrial DNA of European origin, that is, those who had among their ancestors women who emigrated to America from Europe.
According to scientists, fragments of nuclear DNA involved in the life of mitochondria are gradually approaching the "roots" – to African or Indian DNA – due to the pressure of natural selection, which "pulls" nuclear DNA to mitochondrial, closer to the ancestors. As a result, mitonuclear incompatibility in the population becomes smaller and the damage from it decreases.
The authors of the article believe that the study is especially important in light of the recently developed technology of mitochondrial replacement therapy, which consists in replacing the egg with its own mitochondria with donor ones. This technique allows you to fight genetic diseases that occur due to mutations in the mitochondrial genome.
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