The activity of mutant genes is higher in chromosomes obtained from the father

Mammalian genes work like a father

Kirill Stasevich, "Science and Life"

In any animal, genes from both parents are combined in the genome. The notorious double set of chromosomes is formed by combining genetic material from the father and from the mother, so that the chromosomes are divided into homologous pairs, with different variants of the same genes. And if we take a pair of homologous chromosomes, then in the same place in one and in the other we will find a gene encoding, for example, insulin – but the maternal and paternal variants will differ in mutations. 

However, if mammals receive their genes equally, then mutations should be divided equally: both father and mother give the child about the same amount of them. This is true, however, if we evaluate mutations by their manifestation, then paternal ones manifest themselves in offspring more strongly than maternal ones.

Researchers from the University of North Carolina at Chapel Hill experimented with three lines of laboratory mice that genetically differed from each other in about the same way that different people differ from each other. Usually, hereditary effects, the influence of mutations, etc. are studied by crossing animals belonging to the same pure line and almost indistinguishable from each other in genes. So we can observe some phenomenon without worrying about how it will be affected by the individual characteristics of the organism. But if we are going to judge a person by such mice, it is worth remembering that a person does not have any pure lines – since there are no restrictions on crossing – so the highest genetic diversity can influence the effects and phenomena that we observed in pure form on animals in any way. And if we want to see how genetic effects work in real life, then we need to cross different lines between each other – which was done (see the UNC Health Care press release: Genetically speaking, mammals are more like their fathers).

James Crowley and his colleagues "mixed" three mouse lines with each other, with each line acting both from the maternal side and from the paternal side; as a result, nine species of hybrids emerged in the offspring. When the mice grew up, they analyzed the activity of genes in four different tissues, including the nervous tissue of the brain. The data obtained were compared with how active the same genes were in the parents.

The activity of a gene can be determined by the amount of mRNA read from it: the more of it, the stronger the gene works. In the future, mRNA serves as a matrix for the assembly of protein molecules, and here its regulation mechanisms come into play: for example, mRNA can "shut up" or simply degrade. However, as a first approximation, it can be assumed that the amount of mRNA determines the amount of protein, that is, the active gene produces more protein "trait". A huge class of mutations affects the synthesis (transcription) of mRNA – they are called regulatory mutations, and it is with them that complex diseases associated with abnormal activity of a particular gene often begin, such as diabetes, cardiovascular diseases and many others.

It turned out, as the authors of the work in Nature Genetics (Crowley et al., Analyzes of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic), that most of the genes (including those that function in the brain) in offspring reproduced exactly the paternal type of activity. That is, if some gene works as it should, or is not working properly, or is too active, then, most likely, this is the "merit" of the father.

Once again, it is worth emphasizing that we are not talking about all possible mutations in general, but only about regulatory ones, that is, those that affect the activity of the gene (because, for example, there are others that can change the structure of the protein itself, without affecting its quantity or the amount of its mRNA). And, most likely, this is the case with all mammals, that is, if you look like your mother, then you obey your father's instructions regarding the regulation of metabolism or the work of brain neurons. The results obtained make us recall the so-called genomic imprinting (not to be confused with behavioral!) – a phenomenon known to biologists for a long time when the activity of genes depends on their origin. For example, in the same mammals, in the case of a protein called insulin-like growth factor IGF2, only the allele (a variant of the gene) that came from the father works; the maternal IGF2 allele is silent. During imprinting, epigenetic DNA modifications are actively involved, which block any activity of the "unnecessary" gene.

But there are few imprinted genes in mammals, only 95, and imprinting can be both paternal and maternal. Now several hundred more have been added to them with a paternal bias in activity. What kind of molecular mechanisms are involved here remains to be seen. On the other hand, although the authors say that we are dealing with a common pattern for all animals, I would like additional evidence that things are exactly the same for humans, since here it concerns practical issues related to genetic diagnosis and therapy. After all, now it turns out that if an unpleasant mutation is found in your DNA, it is important to know from whom it came to you, from your father or mother – it will depend on how much it can ruin your life.

Portal "Eternal youth" http://vechnayamolodost.ru 05.03.2015