How much Indy does it take to extend life?
For many years, researchers have been studying the influence exerted by mutations of the Indy gene (an abbreviation of the English "I'm Not Dead Yet" – I'm not dead yet) on the metabolism, life expectancy and reproductive health of mammals and fruit flies. So far, these experiments have been carried out only in laboratory conditions.
A new study by scientists from Brown University has radically changed the situation. Based on the results of studying the genomes of fruit flies collected around the world for 60 years, they came to the conclusion that at least one particularly important variation of this gene, which has a significant impact on life expectancy, is widespread in nature.
The variation described by the authors is a naturally occurring insertion of a mobile genetic element (transposon) Hoppel to a specific region of the Indy gene. It was found with different frequency in flies of 17 out of 22 lines from different countries of the world, some of which originate in the middle of the last century. For example, Hoppel carriers are 100% of individuals of the drosophila line contained in captivity, the ancestors of which were captured in Mumbai (India) in 2006, and 55% of individuals of the line originating in 1955 on the island of Oahu in the Hawaiian archipelago.
The prevalence of the Indy gene mutation in the world. Each sector of the pie chart corresponds to a line of fruit flies, which has a different geographical origin from other lines. The area of the shaded zone of each segment is proportional to the frequency of occurrence in the population of the Indy gene with the Hoppel transposon embedded in it. Individuals with such a mutation live much longer than individuals who do not have it (scheme from the article in Aging).
According to one of the leaders of the study, Professor Stephen Helfand, he remembers how in 2000, when he first published an article in the journal Science, the results of which indicate the influence of the Indy gene on life expectancy, several reporters wondered why "useful" mutations of this gene are not found in wildlife.
The results of a study conducted 14 years later demonstrated that this was not the case. At least one of these mutations occurs in fruit flies from distant regions and, accordingly, having very different genotypes. This indicates an important evolutionary role of this mutation.
The researchers analyzed the physiological effects of the Hoppel transposon embedded in the Indy gene on three different drosophila lines. The progenitor individuals of these lines were captured in Hawaii – on the island of Oahu in the 1950s and in the city of Captain Cook in 2007, as well as in the Mexican state of Hidalgo in 2005. In each line there were both individuals-carriers of the Indy-Hoppel complex, and individuals with an unchanged Indy gene.
Observations showed that females heterozygous for this trait laid 10% more eggs than females who had only normal copies of the Indy gene. At the same time, the least eggs were laid by females who had the Hoppel transposon in both alleles of the Indy gene. Apparently, the presence of only one copy of the Hoppel-containing Indy gene in the genome gives insects an advantage in terms of breeding success.
As for life expectancy, both one and two copies of the modified Indy gene had a pronounced positive effect. On day 60, more than 80% of fruit flies with one copy of the altered gene and slightly less, about 80%, homozygotes (with two Indy-Hoppel alleles) remained alive. Among drosophila with two normal copies of the Indy gene, less than 60 reached 60 days%
Despite numerous earlier experiments, researchers still haven't fully figured out how the Indy gene exerts its influence. Apparently, the protein encoded by it is involved in regulating the entry of metabolically important small molecules, such as citrate, into the cytoplasm of the cell. Mutations of this gene affect the concentration of these compounds in the cytoplasm. Some of them effectively mimic the effects of a low-calorie diet, providing an increase in the lifespan of fruit flies and nematodes.
The hypothesis that Helfand and his group wanted to test is that Indy mutations, by changing its activity, regulate the expression of its gene, which can both positively and negatively affect the state of the body. To do this, they measured the levels of Indy matrix RNA encoding the protein product in drosophila cells, which is used as a molecular indicator of gene expression. The results showed that the more copies of Hoppel were embedded in the Indy gene, the higher the expression of this gene. Considering that heterozygous individuals live longer than others and lay the most eggs, the best option is a moderate level of expression of the Indy gene.
Previously, experts were inclined to believe that embedding transposons in genes as a whole has a detrimental effect on the body. This study is one of the few documented cases of the reverse pattern. Moreover, the results obtained indicate that mutations resulting from the embedding of mobile genetic elements may be one of the mechanisms for the emergence of new genes, providing material for natural selection and adaptive evolution.
Article by Chen-Tseh Zhu et al. Indy gene variation in natural populations confers fitness advantage and life span extension through transposon insertion is published in the open access journal Aging.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Brown University:
Longevity mutation found in flies far and wide.
11.02.2014