18 February 2015

Antibodies by inheritance

New carriers of hereditary information

Alexandra Bruter, <url>Trying to understand why in some experiments the results differ from the assumptions of scientists, researchers from Washington University in St. Louis have discovered a new type of inheritance (see the press release Mothers can pass traits to offspring through bacteria's DNA).

An article about this was published the day before yesterday in the journal Nature (Moon et al., Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation).

The acquisition of new knowledge in the science of life cannot do without experiments on animals. This applies to both fundamental and applied research. Experiments on cultured cells are good only as a preliminary stage of research.

If, for example, we are talking about studies of a potential new drug, working only with cells, it is impossible to predict the effect of the drug on different body systems, and it is impossible to determine the entire set of side effects. The desired effect demonstrated by the drug in cell culture may be significantly reduced by some extraneous processes occurring in the body. The same goes for basic research. Many observed phenomena are the sum of events occurring in different systems of the body.

It is obvious to everyone that all people are different. Less obvious, but this scientist has to take into account that all mice are also different. At least, mice from the wild. Therefore, in order to distinguish between the universal effect and the individual characteristics of the animal, a large number of animals take part in the experiment.

In addition, special animals with low phenotype variability are bred for the needs of scientists. They are obtained by closely related crossing. As a rule, such animals are painful, their immunity is weakened, and they would not survive in the wild, but with proper care in laboratories, this does not matter. But when one group of scientists wants to repeat the results of another group (and this is quite an important part of the scientific process; the results must be reproduced, otherwise their value is small), they can buy exactly the same animals in the same nursery and reduce the number of unknown experimental factors.

The idea that animals will be similar to each other is completely based on the concept that the genotype determines the phenotype. In nurseries, animals with similar genotypes are bred, genetic testing is carried out from time to time and they check whether they have become too different from each other, so scientists have the right to hope that they will get animals with very similar phenotypes.

And it turned out that animals with similar genotypes can have different phenotypes. The mice that were supposed to be the same were divided into two groups: with high levels of immunoglobulin A (IgA) in the intestine and with low. These antibodies are present on the mucous membranes, in the stomach and intestines – wherever the sterile inner world of the body comes into contact with the environment full of viruses, bacteria and eukaryotic parasites. In fact, it looked as if some of the animals had a mutation in the genes encoding IgA, but there was no mutation there.

In addition, it turned out that a high level of IgA is important for the health of the gastrointestinal tract. The induction of colitis by laboratory methods was much more successful in mice with low IgA levels.

The main question is what was the basis of the differences between mice with an identical genotype. It turned out that it was all the fault of the bacteria inhabiting the intestines. Most of the intestinal microflora is harmless or even helps the host digest food in exchange for its share of nutrients. When an embryo develops in the womb, it is protected from contact with bacteria, but it meets them already in the birth canal. In animals, mothers actively take care of newborn offspring in the first days, and at this time there is also an intensive exchange of microflora. It is not surprising that in mice that live in clean laboratories and eat sterile factory food, a set of intestinal commensals is inherited from the mother with the same accuracy as nuclear DNA. It is also possible to subsequently exchange microflora with animals living in the same room, if they came from different nurseries.

In this study, the authors were able to prove the relationship between the composition of microflora and the level of IgA and demonstrate the ways of microflora transmission. Their results fully explain where the difference between the animals from which scientists expect identity comes from.

From a fundamental point of view, the inheritance mechanism is of interest in this study, which was almost not mentioned before the appearance of this article. It is generally believed that the phenotype of an organism is determined by the genotype. In the last ten years, the epigenetic theory has been actively developing, according to which not only genes are inherited, but also the level of their activity. Now another mechanism has been added to them – inheritance of microflora. To do this, two conditions had to be met: the microflora would be inherited, and a certain composition of the microflora would be associated with a certain phenotype. In this study, both conditions are met.

Portal "Eternal youth" http://vechnayamolodost.ru18.02.2015

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