More protein – more growth
A new heredity has been found for human growth
Kirill Stasevich, Science and Life (nkj.ru )
We have a number of traits that are clearly inherited, but it is unclear exactly how. This is a tendency to certain diseases, some behavioral features, and even growth - tall parents are likely to have a tall child, but what exactly are the genetic features that work here? Of course, there is no one "growth gene", growth depends on many genes, but even with these genes in hand, it is not always clear what exactly affects growth in them.
When they talk about the influence of a gene on one or another trait, they mean that the same gene always exists in different variations. That is, if a person got some one variant of the gene, then the person will grow up short, and if another variant of the gene, then high. Variants are usually understood as point replacements of genetic letters – nucleotide bases in DNA. Genes, as you know, are encoded in DNA by a sequence of four nucleotide bases, and if one, or two, or more bases suddenly change to others, then the gene, in general, will encode the same protein with the same functions, but this protein will work a little differently. (And if it works completely differently, we will have big problems, and we can talk about pathogenic mutations.) For simplicity, we are now talking about genes encoding proteins, although to complete the picture, we also need to mention the genes encoding independent RNA molecules, which themselves play a big role in the life of the cell, as well as about special sections of DNA that do not encode anything at all, but control the activity of genes.
And if you focus on finding such nucleotide substitutions (which are called SNP – single nucleotide polymorphisms, polymorphism by single nucleotides), then it will be difficult to unravel heredity by growth. Of course, we will find many nucleotide substitutions in genes that affect growth, but these substitutions often turn out to be different in equally tall parents and children. And even taking into account the fact that growth depends on many genes, it will be very difficult to find matches in the inheritance of growth and SNP.
But in addition to nucleotide substitutions, other interesting things can happen to DNA. The genetic mechanism of inheritance of growth becomes much clearer if we take into account tandem repeats of sites in DNA within a single gene. Tandem repetition is when a piece of genetic text is copied end–to-end with the original. We can give an analogy with the text: imagine that the phrase "Tomorrow rains are expected" turned into "Tomorrow rains are expected" – a fragment of the letter sequence was copied twice and formed a tandem repeat.
Such a repeat can be single, double, triple, etc. for the same gene. Now this gene has different variants that differ in tandem repeats (and the repeats themselves may be from different parts of the gene). The protein that will be synthesized from such a gene will be larger: if without repeats, for example, there were 1000 amino acids in it, then with repeats – 2000. Not all proteins can withstand such enlargement, after all, their functions depend on the sequence of amino acids. But there are also those that do not deteriorate, do not break, but continue to work, only now they work a little differently.
Analysis of variability by tandem repeats could reveal hereditary strands for many traits, but the problem is that searching for such repeats in DNA was quite a difficult task until recently. What exactly are the difficulties here is a subject for a separate conversation. However, recently, works have begun to appear, the authors of which quite successfully and with the help of different approaches analyze tandem repeats in the same genes in different people. One of these articles has just been published in Science (Mukamel et al., Protein-coding repeat polymorphisms strongly shape diverse human phenotypes) – in it the staff The Broad Institute applied statistical methods to 118 DNA sequences encoding certain proteins. These 118 sequences (roughly speaking, genes) were taken from the genomes of more than 400 thousand people, about whom it was also known how tall they were, what level of lipoproteins they had in their blood, what level of urea and many other medical and non-medical data.
The researchers found nineteen traits that strongly depended on tandem repeats in the genes. Among these signs was the level of lipoproteins in the blood, and some features of kidney function, and the likelihood of gout, and growth. Depending on the length of tandem repeats in the ACAN gene , the height of different people could differ by 3.2 cm . The aggrecan protein encoded in the ACAN gene works in the intercellular matrix, a substance that fills the space between cells. The aggrecan holds water in the matrix, and it is known that a large aggrecan holds more water. How this affects growth is not yet clear, but the relationship between the aggrekan increasing due to tandem repeats and growth is quite obvious.
The point here, of course, is not so much in growth as in other traits that are influenced by tandem repeats in genes. The level of lipoproteins in the blood can indicate the risk of atherosclerosis, the peculiarities of kidney function can turn into regular dialysis procedures, and if geneticists learn to analyze these tandem repeats in the human genome cheaply and quickly, many of us will be able to take the necessary measures before the real disease comes to them.
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