How Organisms Can Tolerate Mutations, Yet Adapt to Environmental Change
Monday, January 25, 2010
The short answer, according to University of Pennsylvania biologist Joshua B. Plotkin, is that these two requirements are often not contradictory and that an optimal level of robustness maintains the phenotype in one environment but also allows adaptation to environmental change.
Using an original mathematical model, researchers demonstrated that mutational robustness can either impede or facilitate adaptation depending on the population size, the mutation rate and a measure of the reproductive capabilities of a variety of genotypes, called the fitness landscape. The results provide a quantitative understanding of the relationship between robustness and evolvability, clarify a significant ambiguity in evolutionary theory and should help illuminate outstanding problems in molecular and experimental evolution, evolutionary development and protein engineering.
The key insight behind this counterintuitive finding is that neutral mutations can set the stage for future, beneficial adaptation. Specifically, researchers found that more robust populations are faster to adapt when the effects of neutral and beneficial mutations are intertwined. Neutral mutations do not impact the phenotype, but they may influence the effects of subsequent mutations in beneficial ways.
To quantify this idea, the study's authors created a general mathematical model of gene interactions and their effects on an organism's phenotype. When the researchers analyzed the model, they found that populations with intermediate levels of robustness were the fastest to adapt to novel environments. These adaptable populations balanced genetic diversity and the rate of phenotypically penetrant mutations to optimally explore the range of possible phenotypes.
The researchers also used computer simulations to check their result under many alternative versions of the basic model. Although there is not yet sufficient data to test these theoretical results in nature, the authors simulated the evolution of RNA molecules, confirming that their theoretical results could predict the rate of adaptation.
"Biologists have long wondered how can organisms be robust and also adaptable," said Plotkin, assistant professor in the Department of Biology in Penn's School of Arts and Sciences. "After all, robust things don't change, so how can an organism be robust against mutation but also be prepared to adapt when the environment changes? It has always seemed like an enigma."
Robustness is a measure of how genetic mutations affect an organism's phenotype, or the set of physical traits, behaviors and features shaped by evolution. It would seem to be the opposite of evolvability, preventing a population from adapting to environmental change. In a robust individual, mutations are mostly neutral, meaning they have little effect on the phenotype. Since adaptation requires mutations with beneficial phenotypic effects, robust populations seem to be at a disadvantage. The Penn-led research team has demonstrated that this intuition is sometimes wrong.
The study, appearing in the current issue of the journal Nature, was conducted by Jeremy A. Draghi, Todd L. Parsons and Plotkin from Penn's Department of Biology and Günter P. Wagner of the Department of Ecology and Evolutionary Biology at Yale University.
The study was funded by the Burroughs Wellcome Fund, the David and Lucile Packard Foundation, the James S. McDonnell Foundation, the Alfred P. Sloan Foundation, the Defense Advanced Research Projects Agency, the John Templeton Foundation, the National Institute of Allergy and Infectious Diseases and the Perinatology Research Branch of the National Institutes of Health.
Good mutations: Stalking evolution through genetic mutation in plants
Wednesday, January 06, 2010
Good mutations: Stalking evolution through genetic mutation in plants
Thale cress (Arabidopsis thaliana) has one of the smallest genomes in the plant kingdom and is a laboratory darling around the world owing to its relatively short code. First sequenced in 2000, the humble weed has only 120 million base pairs in its genome (humans, by contrast have about 2.9 billion), but it still packs plenty of genetic mystique.
A new study has uncovered the rate of the plant's spontaneous mutations as they happen across generations—a finding that could help illuminate the evolutionary history of plants and selective breeding efforts in the future.
"While the long-term effects of genome mutations are quite well understood, we did not know how often new mutations arise in the first place," Detlef Weigel, director at the Max Planck Institute in Germany, and coauthor of the study which appeared online Thursday in Science, said in a prepared statement.
The group studied genetic changes of five different plant lines across 30 generations. After carefully comparing each full genome, they found that only about 20 base pairs had mutated in each line.
"The probability that any letter of the genome changes in a single generation is thus about one in 140 million," Michael Lynch of the Department of Biology at Indiana University in Bloomington and study collaborator, said in a statement.
Locating these small numbers required some high-powered sequencing. "To ferret out where the genome had changed was only possible because of new methods that allowed us to screen the entire genome with high precision and in very short time," Weigel said. Despite the new sequencing capabilities, the team still rechecked each letter's position 30 times to make sure suspected mutations were being accurately assessed. As high-throughput sequencing becomes more widely available, researchers should be able to conduct more mutation-rate studies. One ongoing study at Michigan State University that is tracking evolutionary change in E. coli, for example, has analyzed hundreds of mutations across 40,000 generations of the bacteria.
The new findings might prove to be more than a simple gee-whiz figure. This study revealed that mutations were occurring at about the same rate across the full genome—not just in specific parts. This might help explain why efforts to keep some plants at bay with single-gene-targeting herbicides are often only briefly successful. It should also hearten researchers who are searching for ways to improve crops—making them more drought-tolerant or better producers—to know that these mutations are likely already occurring. But to truly expedite strategic breeding for many crops, full genome sequencing, as was recently accomplished for corn, will be crucial to giving horticulturalists a genetic map to different traits.
The group has also been able to use the findings to peer back into Arabidopsis thaliana 's genetic past. Previously, researchers had speculated that it and its closest relative, Arabidopsis lyrata, had split about five million years ago. The new genetic data suggests a divergence at least 20 million years ago.
Although these results are from a lowly mustard relative, the data might also have implications for understanding human genetic change.
"If you apply our findings to humans, then each of us will have on the order of 60 new mutations that were not present in our parents," Weigel said. A study published in Current Biology in August estimated that each individual had something more along the lines of 100 to 200 new mutations. Whatever the exact number, the modest mutation rate can have a big impact when spread across some six billion individuals. And even though natural selection usually appears to work on a relatively slow timescale, with so many mutations, nature can be assaying new combinations all the time. "Everything that is genetically possible is being tested in a very short period," Lynch said.
Image courtesy of Wikimedia Commons/Suisetz
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