Genetic based human diseases are an ancient evolutionary legacy

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Genetic based human diseases are an ancient evolutionary legacy

http://www.eurekalert.org/pub_releases/2008-10/m-gbh101608.php

Tomislav Domazet-Lošo and Diethard Tautz from the Max Planck

Institute for Evolutionary Biology in Plön, Germany, have

systematically analysed the time of emergence for a large number of

genes - genes which can also initiate diseases. Their studies show

for the first time that the majority of these genes were already in

existence at the origin of the first cells. The search for further

genes, particularly those which are involved in diseases caused by

several genetic causes, is thus facilitated. Furthermore, the

research results confirm that the basic interconnections are to be

found in the function of genes - causing the onset of diseases - can

also be found in model organisms (Molecular Biology and Evolution).

The Human Genome Project that deciphered the human genetic code,

uncovered thousands of genes that, if mutated, are involved in human

genetic diseases. The genomes of many other organisms were deciphered

in parallel. This now allows the evolution of these disease

associated genes to be systematically studied.

Tomislav Domazet-Lošo and Diethard Tautz from the Max Planck

Institute for Evolutionary Biology in Plön (Germany) have used for

this analysis a novel statistical method, " phylostratigraphy " that

was developed by Tomislav Domazet-Lošo at the Ruðer Boškoviæ

Institute in Zagreb (Croatia). The method allows the point of origin

for any existing gene to be determined by tracing the last common

ancestor in which this gene existed. Based on this information, it is

then possible to determine the minimum age for any given gene.

Applying this method to disease genes, the scientists from Plön came

to surprising findings. The vast majority of these genes trace back

to the origin of the first cell. Other large groups emerged more than

one billion years ago around the first appearance of multi-cellular

organisms, as well as at the time of origin of bony fishes about 400

million years ago. Surprisingly, they found almost no disease

associated genes among those that emerged after the origin of mammals.

These findings suggest that genetic diseases affected primarily

ancient cellular processes, which emerged already during the early

stages of life on Earth. This leads to the conclusion that all living

organisms today, i.e. not only humans, will be affected by similar

genetic diseases. Furthermore, this implies that genetically caused

diseases will never be beaten completely, because they are linked to

ancient evolutionary processes.

Although it was already known that many disease associated genes

occur also in other organisms distant to humans, such as the fruitfly

Drosophila or the round worm Caenorhabditis, the analysis of Domazet-

Lošo and Tautz shows now for the first time that this is

systematically true for the vast majority of these genes. At present

it remains unknown why the more recently evolved genes, for example

those involved in the emergence of the mammals, do not tend to cause

diseases when mutated.

The research results of the scientists from Plön also have some

practical consequences. It will now be easier to identify candidates

for further disease genes, in particular for those involved in multi-

factorial diseases. Furthermore, the results confirm that the

functional knowledge gained about such genes from remote model

organisms is also relevant for understanding the genes in humans.

Original work:

Tomislav Domazet-Lošo und Diethard Tautz

An ancient evolutionary origin of genes associated with human genetic

diseases.

Molecular Biology and Evolution, September 26, 2008; doi

10.1093/molbev/msn214