Species risk extinction beyond ‘speed limit’ of six mutations per genome per generation

Oct 2 : The rate of molecular evolution in organisms cannot be more than six mutations per genome per generation, for beyond this, species run the risk of extinction as their genomes lose stability, a new study by a team of Harvard University scientists has revealed.

Eugene Shakhnovich and his colleagues modelled the stability of proteins required for an organism’s survival, and discovered this essential thermodynamic limit on a species’ rate of evolution.

“While mathematical genetics research has brought about some remarkable discoveries over the years, these approaches always failed to connect the dots between the reproductive fitness of organisms and the molecular properties of the proteins encoded by their genomes,” said Shakhnovich, professor of chemistry and chemical biology in Harvard’s Faculty of Arts and Sciences.

“We’ve made an important step toward finally bridging the gap between macroscopic and microscopic biology,” he said.

Prof. Shakhnovich said, crucial aspects of an organism’s evolutionary fitness could be directly inferred by inspecting its DNA sequences and analyzing how the proteins encoded by those sequences fold.

DNA sequences encode the order of amino acids in a protein, and amino acids act as the protein’s basic building blocks by arranging themselves into a structure that allows the protein to perform its biological function.

He said the research was inspired in part by the longstanding recognition that knocking out essential genes, making them inactive, produced a lethal phenotype, or a physiologically unviable organism.

“From there, we made the simple assumption that in order for an organism to be viable, all of its essential genes — those that support basic cell operations — have to encode at least minimally stable proteins,” said Prof. Shakhnovich.

“What occurs over the long process of evolution is that random mutations can either encode slightly more or less stable proteins,” he said.

He said the find drew a crucial connection between the physical properties of genetic material and the survival fitness of an entire organism.

The team found that for most organisms, including viruses and bacteria, an organism’s rate of genome mutation had to stay below six mutations per genome per generation to prevent the accumulation of too many potentially lethal changes in genetic material.

If enough mutations pushed an essential protein towards an unstable, non-functional structure, the organism would die.

“The existence of a mutation limit for viruses helps explain how the immune system can perform its function. Since viral replication and survival can only occur at a limited rate, the body has a window of time to develop antibodies against infectious agents,” Prof. Shakhnovich said in his study.

“Furthermore, if the mutation rate is high, the size of the genome in question must be small to stay within the bounds of the speed limit – thus organisms that tend to mutate quickly are those with concise genomes, such as viruses and bacteria,” he said.

The study appears in this week’s Proceedings of the National Academy of Sciences (PNAS). (ANI)