Hereditary diseases no new "invention"

Study: Since the evolution of mammals hardly any new disease genes have been added

Artistic representation of a phylostratigraphy © Irena Andreic / Ru &
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Scientists have systematically analyzed the timing of the generation of numerous genes that can also trigger disease. Their studies show for the first time that these genes exist in their overwhelming majority already since the origin of the first cells. Thus, the search for other genes, especially those that are involved in diseases with multiple genetic causes, much easier, according to the researchers in the journal "Molecular Biology and Evolution".

In addition, the results of Tomislav Domazet-Loso and Diethard Tautz of the Max Planck Institute for Evolutionary Biology in Plön confirm that basic relationships about the function of genes that cause disease can also be found in model organisms.

Small change, serious consequences

A small change in the sequence of letters suffices - an A for a C - and a gene that has worked perfectly so far becomes the cause of the disease. By decoding the human genome, thousands of genes have now been identified that, if they carry such mutations, can lead to genetic diseases in humans.

The Online Mendelian Inheritance in Man database identifies more than 4, 000 chromosome regions associated with genetic disorders. And for just over half of these regions, the genes whose mutations are responsible for the onset of human disease are identified. Many of these genes are found in other organisms such as the fly Drosophila or the nematode Caenorhabditis.

Domazet-Loso and Tautz have now subjected these genes to a more detailed analysis. Their goal: the determination of the time of their evolutionary origin. The scientists from Plön used a statistical method developed by Domazet-Loso at the Rowing Boskovic Institute in Zagreb (Croatia) back in 2007, the so-called "phylostratigraphy". display

Determine the origin of each gene

This method makes it possible to determine the origin of any gene that exists today. For this, the data from completely decoded genomes of comparative organisms, representing the entire pedigree of the eukaryotic organisms with cell nucleus and cell membrane, are used. Using a sequence similarity search (BLAST) then determines the last common ancestor, in whose genome the investigated gene can still be discovered. Thus, the first appearance of the gene, ie its minimum age, is accurately determined.

"In fact, for the first time, this systematic age determination of those genes responsible for certain diseases has shown that they exist in an impressive majority since the origin of the first cells, " explains Tautz. Large groups of these genes were formed during the evolution of multicellular organisms more than a billion years ago and at the time of the evolution of bony fish approximately 400 million years ago. Surprisingly, since the evolution of mammals, hardly any new potential disease genes have been added, "says the evolutionary biologist.

Genetically related diseases evidently relate primarily to evolutionary cellular processes that have already developed in the early stages of organic life. And that leads to the conclusion that all living organisms today may be affected by similar genetic diseases.

Research on model organisms makes sense

"Ultimately, we can never completely defeat genetically-related diseases because they affect processes that have been unchangeably established in evolution, " says the Max Planck researcher. It remains puzzling why developmentally young genes, such as those necessary for the development of mammals, seldom cause disease when they carry mutations.

The results of the Pl ner researchers have practical consequences, as they justify the use of model organisms in biomedical research: Since, as shown, evolutionary old processes are affected, it is to be expected that even with thread winders ( C. elegans) or flies (Drosophila) that are not closely related to humans, basic relationships can be explored that can be used for appropriate therapeutic approaches in humans.

(idw - Max Planck Society for the Advancement of Science, 16.10.2008 - DLO)