Protected genes : At the wheel of evolution

"Chance rules nature, is a dogma of biology. German plant geneticists have now shown that mutations do not accumulate in the genome in an uncontrolled manner, but rather that the organism protects some genes in a targeted manner.

 

Ever since Charles Darwin, evolutionary biology has paid homage to chance and formulates sentences like "Evolution wants nothing, plans nothing and has no goal". Mutations - according to one of their most important dogmas - occur randomly and do not care about the consequences they produce. Only its opponent, natural selection, decides which genes change faster and which change more slowly. Categories such as chance and directionlessness are therefore considered basic assumptions of evolutionary biological thinking. This thinking was cemented by the Nobel Prize in Medicine awarded to Salvador Luria and Max Delbrück in 1969. Twenty-six years earlier, the scientists had shown that bacterial populations always also contain bacteria that are already resistant to viruses that they have not yet encountered and which they therefore also not know. The mutations that mediate resistance must therefore have arisen without the help of these viruses - just randomly and undirectedly.

 

A publication by Detlef Weigel, Gray Monroe and other colleagues in the journal "Nature" now scratches at these basic assumptions. Weigel is Director at the Max Planck Institute for Biology in Tübingen and Monroe Professor at the University of California in Davis. 

 

The scientists were able to show that the mutations in the genome of the weed Arabidopsis thaliana, one of the most important scientific model plants, are by no means as randomly distributed across the genome as previously assumed. Rather, genetic changes occur more frequently in some places and less frequently in other places. The frequency of mutations correlates with the importance of the genes for the plant's ability to survive and reproduce. The mutation rate is lower where the essential genes of the weed are located, and higher in the regions where the less essential genes are located.

 

The mutations are also unequally distributed within the so-called coding and non-coding regions of a gene. Coding DNA sequences, i.e. those that are directly responsible for the synthesis of a protein, were only mutated half as often as the non-coding sections that lie before and after the respective genes. 

 

Essential genes showed two-thirds fewer mutations than non-essential genes. 

 

"It's just as if evolution were playing with loaded dice," says Weigel. "Plants have evidently evolved a way to protect their most important genes from mutations so that they can survive better. This is a whole new perspective on how mutations arise and how evolution works.”

 

What Arabidopsis in the Lot?

 

What are these findings based on? Weigel and his colleagues carried out so-called mutation accumulation experiments with hundreds of Arabidopsis plants, in which natural selection was almost completely eliminated, and examined more than a million newly occurring mutations. By eliminating natural selection, the scientists were able to analyze all mutations, including the harmful ones, which normally disappear quickly under the pressure of selection. This feat was only possible because Arabidopsis has a relatively small genome with 120 million base pairs. How does the unequal distribution of mutations in the weed genome come about?

 

Ninety percent of the variance can apparently be explained by different epigenetic marks and DNA packaging proteins. These changes in the genome – protective caps, so to speak – determine how open and accessible the genetic material is in its sphere of influence and thus how well the DNA can be repaired in the event of a mutation, because the repair enzymes cannot do their job without direct access to the DNA strand .

 

 "Our most important finding is that there is obviously a class of genes in the cell that are marked differently than other genes and that are repaired particularly well and efficiently because of these markings," says Weigel. "That surprised us."

 

Now, what keeps Arabidopsis more in balance—the uneven distribution of mutations and the efficient repair of essential genes, or the negative or purifying selection that removes harmful and deleterious gene versions? 

 

Weigel and his colleagues were able to show that evolution—at least in Arabidopsis—is more strongly influenced by the efficient repair of essential genes and less by purifying selection. Because the weed's essential genes tolerate little variability, the plant obviously does not wait for that the selection removes the damaged allele, but repairs the error immediately and precisely.

 

Opportunities for plant breeding

 

"Nevertheless, the essential genes also change over time," says Weigel, "albeit more slowly than other parts of the genome." Regions with less important genes tolerate more variability. Here the selection is given more scope to select new and useful variants. The results are remarkable in several respects. For one thing, they change the picture that evolutionary biology has had of the forces behind natural variation. On the other hand, they also have very practical consequences.

 

If Arabidopsis protects its most important genes against mutations with special markers on the genome and proteins, the human genome may also be better protected, for example against mutations that cause cancer. 

 

But plant breeding could also benefit. If you know which regions of the genome are particularly susceptible to mutations and which are less so, natural variation can be better controlled. In any case, chance is not the only engine of evolution."