Humans and mutants
Kirill Stasevich, Compulenta
The reason why genetic diseases are becoming more common in the modern world lies not only in a polluted environment teeming with mutagens. As scientists from Cornell University (USA) report in the journal Science, new, previously unseen mutations began to manifest only because there were more of us (Recent Explosive Human Population Growth Has Resulted in an Excess of Rare Genetic Variants).
The frequency of a particular mutation can be predicted using the methods of population genetics, which combines the tools of classical genetics with the provisions of evolutionary theory. The main parameters that are taken into account in this case are the size of the population, its dynamics, the level of mutagenesis, the nature of the mutation we are interested in. This makes it possible to predict the future of a genetic deviation – whether this mutation will gain a foothold in the population or disappear, and how soon it will happen. However, according to the authors of the article, conventional mathematical models are not adapted to the accelerated population growth of the species.
And this is exactly what happened to humanity: over the past ten thousand years, the number of people has jumped from several million to 7 billion, with the greatest acceleration occurring in the last two thousand years, or in the last hundred generations. Of course, even within the last period of time, this growth was irregular, for some time the number of mankind grew gradually, until general progress made human existence more comfortable and safe. To assess the genetic dynamics of a population, researchers usually model its growth from some initial number of individuals. In this case, it was shown that the genetic dynamics in human populations is better estimated in a sample of 10 thousand individuals – against several dozen that were used in previous models. The old models, based on linear rather than exponential population growth, gave a five hundred percent error in predicting mutation frequencies. It should be emphasized that here, first of all, the nature of growth is important: the gradual, linear growth of the population gives time for rare mutations to leave the gene pool.
The population explosion has led to the fact that many rare gene variants are much more common than expected. Thus, natural mutagenesis has a huge field for work, and in the future humanity is waiting for new mutations caused from oblivion by a skew in population dynamics. Perhaps the fantastic "X–Men" will become a banal reality - and will not come out of secret laboratories, but will be formed naturally by evolutionary and genetic means.
It would hardly be a big exaggeration to say that almost every one of us is already a mutant in some way. But first of all, of course, the results obtained will allow us to assess in a new way how much more dangerous genetic diseases are, from the simplest to complex ones like autism, which can develop due to dozens and hundreds of different mutations.
The explosive growth of the human population was supposed to increase the frequency of many rare mutations, which until now geneticists had not paid attention to. The researchers analyzed theoretical models to find out which one is better suited to describe the growth of the human population. And recently, the theory received experimental support: two articles appeared in the journal Science (Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes and An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People), the authors of which fully confirm the assumption of an increased frequency of rare mutations in the genome of modern people.
Here are some numbers. Researchers from the University of Washington in Seattle (USA) read 15,585 genes in 2,440 people and found that 86% of them had gene variants that are considered rare. It should be said here that of all the mutations traditionally associated with medical consequences, 95% belong to a rare group. The second project was carried out by a team from the University of California, Los Angeles (USA). Its result: 202 sequenced genes in 14 thousand people, 95% of gene variants turned out to be rare. At the same time, 74% of mutation types were detected in no more than two people. Such a crop of rare genetic variants was collected thanks to a special method of reading genes, when the same "letter" in DNA was analyzed almost a hundred times.
The columns indicate the read genes, their height indicates the number of variants of these genes.
The probability of detecting most mutations is less than 0.5%, and to see them,
more genetic material is required
(drawing by the authors of the study).
The significance of these results for genetics in general and for medical genetics in particular, as they say, is difficult to overestimate. Population dynamics models could only assume the probability of an increase in the frequency of rare mutations. But specific numbers and specific gene variants can only be learned from such experimental and monstrously time-consuming studies. In recent years, geneticists have been intensively hunting for mutations that would help explain the origin of many hereditary genetic diseases. But the usual, easily detectable mutations have consistently proved insufficient to explain the disease. Now, with the results obtained on rare mutations, much in medical genetics can become clear.
At the same time, researchers have yet to learn how to analyze this kind of data. Firstly, it is obvious that in order to identify genetic variants, it is sometimes necessary to use a huge amount of material - DNA samples from thousands and tens of thousands of people. Secondly, the distribution and manifestation of these mutations may depend on a specific population, that is, the same gene variant may affect residents of the Central United States and the Central Russian Upland in different ways. And finally: according to the researchers, each person from those whose DNA they analyzed carries an average of 25 to 31 mutations. To assess the chances of getting a genetic disease, you need to be able to understand all the subtleties of this mutational bouquet.
Portal "Eternal youth" http://vechnayamolodost.ru18.05.2012