Article: Beyond a 'speed limit' on mutations, species risk extinction

Beyond a 'speed limit' on mutations, species risk extinction

Harvard University scientists have identified a virtual "speed limit" on the
rate of molecular evolution in organisms, and the magic number appears to be
6 mutations per genome per generation -- a level beyond which species run
the strong risk of extinction as their genomes lose stability.

By modeling the stability of proteins required for an organism's survival,
Eugene Shakhnovich and his colleagues have discovered this essential
thermodynamic limit on a species's rate of evolution. Their discovery,
published this week in the Proceedings of the National Academy of Sciences,
draws a crucial connection between the physical properties of genetic
material and the survival fitness of an entire organism.

"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," says 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."

According to Shakhnovich, crucial aspects of an organism's evolutionary
fitness can 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.

The research was inspired in part by the longstanding recognition that
knocking out essential genes, making them inactive, produces 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," says
Shakhnovich. "What occurs over the long process of evolution is that random
mutations can either encode slightly more or less stable proteins."

If enough mutations push an essential protein towards an unstable,
non-functional structure, the organism will die. Shakhnovich's group found
that for most organisms, including viruses and bacteria, an organism's rate
of genome mutation must stay below 6 mutations per genome per generation to
prevent the accumulation of too many potentially lethal changes in genetic
material.

The existence of a mutation limit for viruses helps explain how the immune
system can perform its function. Because viral replication and survival can
only occur at a limited rate, the body has a window of time to develop
antibodies against infectious agents. 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.

The Shakhnovich speed limit also offers an explanation for observed
differences in genome sizes between organisms with genome error
correction -- such as bacteria, mammals, birds, and reptiles - and those
without, such as RNA viruses: In more complex organisms, cells have evolved
correction systems to detect and fix errors in DNA replication. These
systems drastically reduce the number of mutations per replication,
increasing the mutational stability of the genome and allowing more
intricate and delicate biological systems to develop without the risk of
interruptive mutations.

"It's an interesting corollary because it suggests that there is a
fundamental tradeoff between evolutionary security and adaptive flexibility:
Larger, more complex organisms have to have error correction to protect
organismic viability, but this means the rate of evolution slows down
significantly," Shakhnovich says. "As organisms become more complex, they
have more to lose and can't be as radically experimental with their genomes
as some viruses and bacteria."

Source: Harvard University
http://www.physorg.com/news110478853.html

Posted by
Robert Karl Stonjek


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