25 February 2019

All in Dad

A Saudi laboratory has created worms whose children receive genes only from their fathers

Maxim Abdulaev, "The Attic"

Worms that violate the rules of genetic inheritance have been created in the laboratory of the King Abdullah University of Science and Technology (KAUST, Saudi Arabia). The nuclear genome of children from modified males contains only paternal genes, and not both parents, as it happens normally. They get only mitochondria from their mother.

In the genetic sense, we are the children of both our parents equally, 50-50. Normally, most diploid organisms, including humans, receive two copies of the same gene – the paternal and maternal, and each of our cells carries the DNA of both parents. But sometimes events happen that break the usual course of things, and different cells and tissues carry only the genes of the father or mother. Biologists call this homogenous dysomy. It can cause deviations from normal development and diseases, for example, Prader-Willi syndrome and Angelman syndrome. To better study how the distribution of parental genes throughout the body affects development, scientists experimented with a typical model organism – a nematode Caenorhabditis elegans.

Article by Artiles et al. Assessment and Maintenance of Unigametic Germline Inheritance for C.elegans is published in the journal Developmental Cell.

To cause dysomy artificially, scientists used the GPR-1 gene. It is responsible for the formation of microtubules that pull chromosomes apart at different ends of the dividing cell. The researchers constructed a gene based on it, the expression of which was higher than usual, using a promoter from another gene. In addition, scientists inserted several introns into it to confuse the Piwi protein, which makes unnecessary and alien genes silent. In addition, a fluorescent label was inserted into the whole structure. Scientists introduced the resulting gene into the nematode, after which they selected individuals in whom this gene was successfully integrated into the genome.

Normally, at the first division of the zygote, chromosomes from both parents fall equally into each of the two cells. But due to the fact that the GPR-1 gene was more active than usual in modified worms, the separation of chromosomes occurred faster, and they did not have time to mix. The resulting mutants (males) were crossed with normal individuals, and by the glow in the tissues they were able to determine the degree of mosaic of the offspring. Already in the second generation, it was possible to obtain individuals in whom all nuclear genes were only paternal. According to the scientists, their methodology "will be of considerable interest to the research community studying worms, as well as to scientists working on other model objects for whom this approach can become a guide to action." This is how the press release of the King Abdullah University Rules of inheritance rewritten in worms quotes the words of lead researcher Karen L. Artiles.

The idea of using "forced" inheritance in order to spread the property that people need in the population (gene drive) is now receiving great attention from scientists: this way, for example, you can get rid of malaria or the Zika virus, which are spread by mosquitoes. The current development can also be considered as a similar "engine".

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