Disease is as Old as Life
Tree of life, divided between major cell types, those with a nucleus (eukaryotes) and without a nucleus (prokaryotes: the bacteria and archaea). A new study shows that disease-related genes could trace back to the very first cell.
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 Ruder Boškovic 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.
DNA stores the genetic information necessary for life. In 2003, the Human Genome Project deciphered human DNA and uncovered thousands of important genes.
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.
By sequencing the human genome alongside the genomes of other organisms, scientists have been able to compare the sequences and understand the genetic relationships between different forms of life on Earth.
Credit: Imperial College London
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.