Where are the most mutants?
Yuri Stefanov, "Biomolecule" based on the materials of Nature News.
Several research groups are trying to determine which of the human races' genomes contain more mutations and how dangerous these mutations are for its representatives. The results of the work show that in the DNA of Europeans, malicious changes are somewhat more common than, for example, in Africans. However, it is not really clear what this means, and whether this is really the case.
Recent studies conducted at Cornell University show that among Americans of European descent, the percentage of harmful mutations in the genome is slightly higher than among African Americans. But these conclusions are already being criticized, which suggests the possibility of a new round of disagreements regarding the interpretation of scientific data.
Carlos Bustamante's group studied the genomes of 20 European Americans and 15 African Americans for the number of single-nucleotide substitutions in them. Moreover, the data obtained by the researchers confirmed the well–known hypothesis that after small groups of people left the African continent, they had to go through the so-called "bottleneck" - a period characterized by a small population and leading to the fact that many alleles, and therefore single-nucleotide substitutions, are eliminated from the population.
Scientists believe that after passing the bottleneck, the population of Europeans began to increase rapidly, as a result of which the accumulation of new mutations went faster than the old ones had time to filter out. As a result, it turned out that the European population is characterized by less overall genomic diversity, but at the same time the relative number of harmful genetic changes in it is potentially greater.
Alexey Kondrashov, a population geneticist currently working at the University of Michigan, disagrees with these conclusions. He argues that the data obtained can be interpreted differently, and populations of Europeans and Africans are in fact burdened with the same mutational burden.
The problem boils down to the difference in the analysis of the results. Bustamante's team analyzed 39,440 localities of single nucleotide polymorphisms (SNP, from English single nucleotide polymorphism), comparing the nucleotide in this position with the one in the same position, but in the genome of chimpanzees, the closest evolutionary relative of humans. Then the "non-ancestral" SNPs were checked for whether they are synonymous or not, that is, whether they lead to substitutions in the amino acid sequence of proteins, and, therefore, whether they can be potentially harmful.
The computer programs used in the work distributed non-synonymous substitutions into three groups: "sparing", "possible pests" and "most likely pests". (The diagram shows one of the variants of gene dysfunction as a result of SNP: due to the replacement of one nucleotide, the triplet encoding the next amino acid turns into a stop codon that stops protein synthesis on the ribosome.) As a result, it was found that African Americans had 47.0% of non-synonymous substitutions in their genomes, and Americans of European origin had 55.4% of such substitutions. Moreover, Africans had about 12.1% of the most harmful substitutions, and Europeans had 15.9%. The difference is small, but statistically significant.
However, Kondrashov points out that Bustamante's group, among other things, estimated the total number of non-synonymous (as well as "possibly dangerous" and "probably dangerous") replacements among Americans. At the same time, in fact, they found out that the number of non-synonymous, possibly dangerous and probably dangerous substitutions in the genomes of the European part of the population and the African part is actually about the same, which follows from Figure 1 of the original publication. According to Kondrashov, the data presented in the figure should be interpreted differently. They say that two populations carry the same number of potentially dangerous nucleotide substitutions. The title of the article misleads the reader.
Bustamante disagrees with this, insisting that this drawing simply reflects the genotypes of the people involved in the study. Also, according to him, their group does not seek to draw conclusions from the data obtained that one population is characterized by a higher overall fitness than another, since it is impossible to say exactly how the identified SNPs will actually affect the health and physical condition of specific people.
Andy Clark, another co-author of the paper, emphasizes that relying only on a statistical description of an entire population, it is extremely difficult to predict individual risk for individual individuals. "The population features we have discovered still say absolutely nothing about whether any American of European descent is more exposed to some risks than any African-American," says the researcher.
Original publication: Kirk E. et al., Proportionally more deleterious genetic variation in European than in African populations. Nature 451, 994–997.
Portal "Eternal youth" www.vechnayamolodost.ru22.02.2008