Thursday , March 4 2021

What the axolotus genome can teach to human medicine



The axolot is a cheerful amphibian with four legs, a crown of galls with a feathery texture and a long tapered tail fin. It may have a pale pink color or be golden, gray or black, spotted or smooth, and his facial expression is similar to that of slightly smiling emoji. This creature is unusual among amphibians because it does not undergo a metamorphosis: he reaches sexual maturity and spends his entire life as a giant tadpole.

According to an Aztec legend, the first of these smiling salamanders was a god who took this form to avoid being sacrificed, hence its name in Nahuatl, axolot. Axolotes are facing an uncertain future. They can only be found in the canals of Lake Xochimilco, in the extreme south of Mexico City, where they were affected by the degradation of their habitat and the introduction to the channel of fish that eat the plants where the axolotes lay their eggs.

In addition, captive axolotes now thrive in laboratories around the world. In an article published Jan. 24 in Genome Research, a team of researchers reported the most comprehensive mapping of amphibian DNA to date. This work paves the way for future advances in regenerative human medicine.

Many animals are able to perform some kind of regeneration, but it seems that the axolots have practically no limits in their ability to do so. As long as they do not cut their heads, they can "create an almost perfect replica" of almost any part of their body., including half of his brain, explained Jeramiah Smith, assistant professor of biology at the University of Kentucky and author of the new article. To understand how they developed these healing superpowers, Smith and his colleagues reviewed the amphibian DNA.

The size of its genome is ten times larger than the human, then it was not a simple fact to analyze the genetic map of the axolot. "It is huge"said Melissa Keinath, a postdoctoral fellow at the Carnegie Institution for the Sciences of Baltimore and co-author of the article.

From an earlier study, Keinath and his colleagues mapped over 100,000 pieces of DNA and grouped them according to their chromosomes, the structures that contain the genetic material in the nucleus of each cell. The genome they collected from the axolot is the largest genome that was compiled with this level of detail.

The scientists used an approach called genetic mapping by linkage, which takes advantage of the fact that DNA sequences that are physically close to one chromosome are often inherited together.

To identify the specific axolote DNA, the researchers contrasted the axolotes with tiger salamandersclose relatives. They crossed the axolots with the tiger salamanders and compared these first generation hybrids with the pure axolotes.

After tracing patterns of genetic inheritance in 48 of these second generation hybrids, the researchers were able to infer which DNA sequences belonged to the axolotes and where they were physically close to the fourteen amphibian chromosomes (Humans have a greater number of chromosomes, but those of the axolot are much larger).

It was like "joining fourteen linear puzzles"said Randal Voss, a professor of neuroscience at the University of Kentucky and co-author of the study.

In the process of validating its results, identified a genetic mutation that causes a heart defect commonly studied in axolotes, Thus, their research will accelerate the future process of scanning the axolotl genome for mutations.

Learn how DNA is positioned along the chromosomes of amphibians. "This allows us to start thinking about functions and how genes are regulated"said Voss. Much of the genome, for example, consists of non-coding DNA sequences that activate and deactivate specific genes. Often, these non-coding sequences occur on the same chromosomes as the genes with which they interact.

"Once these relationships are known, we can ask questions about whether the same type of control appears in other animals, such as humans.""said Jessica Whited, a professor and regeneration specialist at Harvard Medical School, who was not involved in the study.

He explained that this will help scientists to understand if there are predictable ways of "to make humans more like axolots," the fantastic regenerators of the animal kingdom.

Copyright: c.2019 New York Times News Service


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