Unexpectedly Small Effects of Mutations in Bacteria Bring New Perspectives
ScienceDaily (Nov. 7, 2010) — Most mutations in the genes of the Salmonella bacterium have a surprisingly small negative impact on bacterial fitness. And this is the case regardless whether they lead to changes in the bacterial proteins or not. This is shown by Uppsala University scientists in an article being published November 5 in the journal Science.
Under a very high magnification of 25000X, this colorized scanning electron micrograph (SEM) revealed the presence of a single Gram-negative Salmonella typhimurium bacterium, which was imaged right at the point where it was undergoing the process of cell division, resulting in the formation of two separate organisms. (Credit: CDC/Janice Haney Carr)
The researchers have examined the impact of mutations on the rate of growth of the Salmonella bacterium and show that most mutations have generally very small effects. Moreover the negative effects are of the similar magnitude for changes that lead to substitution of amino acids in proteins (so-called non-synonymous mutations) as for mutations that do not change the protein sequence (so-called synonymous mutations).
"The findings open an entirely new chapter for experimental studies of mutations and show that we need to change our view of how mutations lead to negative effects," says Professor Dan Andersson, lead author of the study.
A central question in evolutionary biology, medical genetics, species-conservation biology, and animal breeding is how and why mutations affect an organism's capacity to survive. Usually these questions are studied in DNA sequence analyses from which conclusions have been drawn about what mutations are most common and have become established in the DNA of the organism.
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Science 5 November 2010:
Vol. 330. no. 6005, pp. 825 - 827
DOI: 10.1126/science.1194617
Mutational Robustness of Ribosomal Protein GenesPeter A. Lind,1 Otto G. Berg,2 Dan I. Andersson1,*
The distribution of fitness effects (DFE) of mutations is of fundamental importance for understanding evolutionary dynamics and complex diseases and for conserving threatened species. DFEs estimated from DNA sequences have rarely been subject to direct experimental tests. We used a bacterial system in which the fitness effects of a large number of defined single mutations in two ribosomal proteins were measured with high sensitivity. The obtained DFE appears to be unimodal, where most mutations (120 out of 126) are weakly deleterious and the remaining ones are potentially neutral. The DFEs for synonymous and nonsynonymoussubstitutions are similar, suggesting that in some genes, strong fitness constraints are present at the level of the messenger RNA.
1 Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123 Uppsala, Sweden.
2 Department of Molecular Evolution, Evolutionary Biology Centre, Uppsala University, SE-75236 Uppsala, Sweden.
* To whom correspondence should be addressed. E-mail: Dan.Andersson@imbim.uu.se
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