Gene diseases are an unavoidable property of all living things. Most of the genetic diseases are associated with genes inherited from the most primitive organisms. Billions of years of evolution have made neither individual genes nor the functions they perform more resistant to mutation
Each human cell can be compared to a huge factory, in which more than twenty thousand working genes together do one common cause. The products of gene labor - proteins - are used both in the construction of the plant itself (such proteins are called structural), and as tools of labor - such as, for example, various enzymes involved in a myriad of chemical reactions in cells. By the way, there are much more artisans making tools than brick-makers, concrete workers, and even builders.
There are separate structural elements in a plant, proteins-chiefs and proteins-foremen, starting various processes, numerous systems that support the life of the plant and allow it to function as prescribed by the genetic code. Continuing the analogy, the whole organism can be imagined as a huge state with a diversified industry, regulatory bodies and institutions, and even a large army of officials.
True, not a single state in the world can come close to be compared in terms of the complexity of its structure with any "primitive" fish from the Jurassic period.
By no means all workers are born ideal: during reproduction, mutations inevitably appear in genes. Some of the workers have no hand, some have a thorn in their right eye, some were born with a hunchback. All these defects inevitably affect the quality of the product they produce - unlike humans, genes cannot voluntarily switch to producing something that their limited abilities do not harm.
Hereditary diseases and gene diseases
a group of diseases resulting from DNA damage at the gene level. The term gene diseases is used for diseases associated with a single gene.
However, factories and whole organisms can often continue to work even being built from, speaking conditionally, triangular bricks - not to mention the loss of some signaling function in the cell. In these cases, they speak of congenital diseases. To date, about one and a half thousand genes have been cataloged, certain mutations of which lead to various phenotypic changes in the body, but still allow a person to be born.
Tomislav Domazet-Losho and Dietard Tautz of the Max Planck Institute for Evolutionary Biology in Germany asked which genes in human DNA are most susceptible to such changes. Where, in which shops of our cell factories do the workers who produce the most waste work?
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And the most interesting - what stages of biological evolution gave us the most bunglers?
To deal with this issue, the scientists applied the methodology of "philostratigraphy" developed by them. In recent years, the genomes of organisms located on various branches of the evolutionary tree have been deciphered, and by the presence of similar genes on different branches, it became possible to track at what level a particular gene appeared. Modern data allow Domazet-Losho and Tautz to trace 19 such strata - from bacteria, to multicellular, mammals and primates, right up to humans. The results of this analysis were accepted for publication in Molecular Biology and Evolution; the scientists did not distinguish between diseases caused by damage to one gene and polygenic causes.
Different genes of our body arose at different stages of evolution, and most of them were present in the most distant ancestors of the "crown of creation". It's hard to believe, but more than half of our genes were still present in one form or another in unicellular organisms, and most of this half arose even before the appearance of nuclei in cells. But the entire development of mammals added only about 10% of the total number of genes in our body.
Simple logic dictates that the genes responsible for the most basic cellular processes were inherited from the most ancient organisms. Therefore, mutations in them should lead to defects incompatible with life, and they cannot fall into the category of "congenital", which presupposes this very birth. In addition, these genes have been under the influence of the selection process for billions of years and could somehow “settle down” in a form for which mutations are not so important.
At the same time, the genes that separate humans from apes - not God knows what difference in the global evolutionary picture - are not so important. Well, what prevents a person from being born covered in skin or incapable of mathematical analysis? And what is a million years compared to billions? Therefore, scientists believed that among novice genes there will be a greater proportion of those that lead to congenital diseases.
It turned out that everything is quite the opposite - genetic diseases are more often associated with ancient genes
As the analysis of almost two thousand genes that cause various congenital diseases shows, we still get sick because of the genes inherited from our most distant ancestors. And those innovations that nature first implemented in mammals almost never lead to genetic diseases.
At the same time, we are not talking about absolute values - there are simply more ancient genes, but about relative ones. If out of 8 thousand genes of the most ancient philostratigraphic level, slightly less than a thousand are associated with genetic diseases, then among the two thousand genes that appeared over 100 million years of development of placental mammals, there are less than a dozen such “disease-causing” genes. Most of all, the share of such genes among those relics that we got from precellular organisms and the last precursors of multicellular organisms that flourished during the famous "Cambrian Explosion".
The number of genes at different levels of philostratigraphy, located horizontally. All genes of the human body are shown in blue, genes associated with genetic diseases are shown in red and green. The levels corresponding to individual peaks are labeled. // Domazet-Loo & Tautz / Molecular Biology and Evolution
The authors do not draw any confident conclusions from their unexpected result, limiting themselves to the remark that hereditary diseases seem to be an inevitable component of life itself. In addition, they note, their work makes the biological purpose of those genes that have appeared in our country in the last millions of years - for example, those one and a half thousand that are characteristic of primates even more murky.
However, the work also has an unusual practical sound. Experiments on mice are now considered the "gold standard" in the study of genetic diseases. But if most of them can be modeled on nematodes and fruit flies, why waste time, money and effort working with mammals? According to the authors, if we are talking not about biological function, but about purely theoretical questions such as the causes of gene diseases, it is better to work with those model organisms in which these diseases have arisen.