Minimal human genome

Kirill Stasevich, "Science and Life" based on the materials of Science: The 3230 genes you can’t do without. 

In biology, there is a concept of a minimal genome – a minimal set of genes, without which an organism will not survive. Of course, there are a lot of questions about this concept. For example, what kind of organism are we talking about? You can take a single–celled bacterium, or you can take a very, very multicellular person - they are so different in lifestyle that their set of necessary genes will obviously also be different.

Again, there is a "lifestyle" item. Under what conditions will the minimum genome be sufficient? The same bacterium can get into an exceptionally favorable nutrient medium, with ideal indicators of temperature, salt content, nutrients, etc., or, on the contrary, switch to a hungry ration, and even experience an increase in salinity or acidity. And the set of genes necessary for survival in both cases will be different. Therefore, when discussing the minimum genome, it is often stipulated that it is about favorable living conditions. 

In general, the idea that some genes are more necessary than others arose relatively long ago: for example, back in 1996 Arkady Mushegyan and Evgeny Kunin estimated the minimum required genome for a bacterial cell at 256 genes; in 2004, other researchers proposed a set of 204 genes. The minimal genome was built on a comparative analysis of several bacterial genomes; if we talk about a specific organism, then we inevitably have to recall the Mycoplasma genitalium bacteria, pathogens of diseases of the human genitourinary system – it has only 517 genes, of which 482 encode proteins; 382 of them are vital. The mycoplasma genome was considered the smallest for some time, the DNA of several more microorganisms that can only exist as symbionts inside the host cells has not yet been read. So far, the champion here is the bacterium Carsonella, which lives in the cells of leaf blocks – its genome contains only 182 genes with protein information.

Bacteria are bacteria, and if you try to estimate the minimum number of genes in a person? This is exactly what a research group led by Daniel MacArthur from the Broad Institute tried to do. It is possible to separate important genes from unimportant ones if we assume that important genes will be completely or almost completely similar to each other in different people. It is known that small changes in the sequences in which one individual differs from another can slip through in genes; such changes may not affect the work of the protein encoded by the gene at all, or they may affect only slightly. But in the case of important genes, their modifications are very likely to have a bad effect on the body, and it is unlikely to survive. As for unimportant genes, they can, under certain conditions, afford to work not very well without putting our lives in danger. 

And so the researchers undertook to compare the genes of 60 thousand people with each other (it is worth clarifying that they compared only exons, that is, those sections of genes that carry information about the sequence of amino acids in proteins). In total, we managed to find 10 million differences. 

On the other hand, for each gene, the theoretical number of variants that it would have received if they had appeared in it by chance and remained that way was estimated. The result of the theoretical estimate was compared with what was obtained during the comparative analysis of real DNA sequences (taken, recall, from 60 thousand people). As expected, some genes easily "treated" variations in their own sequence, while others, on the contrary, tried to get rid of them. Having counted the genes in which there were no or almost no changes, the authors of the work received the figure 3230 – that is how many human genes cannot afford any, even the slightest changes in functioning. That is, we can say that these 3230 are the vital genetic set of a person. (Recall that in total, the human genome has, according to various estimates, from 20 to 25 thousand genes.)

Obviously, modifications in the sequences of such genes immediately lead to some serious disorders, either during embryonic development, so that a person does not even have time to be born, or after birth, in childhood or early adolescence (a person dies before he has time to give birth to children). Indeed, about 20% of the 3230 described are known to be associated with various diseases, but the function of most of the remaining genes has yet to be clarified. The results obtained can be used for medical purposes: it is obvious that the search for the genetic causes of certain diseases is best to start with the "minimum genetic set". 

The new data still exists in the form of a preprint, there is no article with them yet. It is possible that by the time of official publication, after all the comments of the reviewers, the number of genes will somehow change. However, it may change like this: who knows, maybe if we take an even larger set of sequences for analysis, the list of necessary genes will increase? Let's not forget that our genome, like any other, consists not only of coding sequences (that is, those that directly carry information about proteins) – in DNA there are a lot of regulatory sites, promoters, enhancers, insulators, sites encoding regulatory RNAs, and among them, of course, there are vital ones. 

By the way, one of the tasks of determining the minimum genome is to create an organism literally from scratch. In other words, can we, knowing the genetic set of the minimal genome, create a living bacterial cell, even if it requires exceptionally favorable conditions for itself? With bacteria, by the way, they are already trying to do this; well, someday it will come to a person. 

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16.11.2015