The Most Extensive Pictures Ever of DNA Mutation
Scientists have produced one of the most extensive pictures ever of mutation processes in the DNA sequence of the E.coli bacteria
The work being done at Indiana University helps eluminate important new information about the molecular nature of mutations and how fast heritable change occurs.
By analyzing the exact genomic changes in the model Escherichia coli E. coli that has undergone over 200,000 generations of growth in the absence of natural selection pressures, the team (led by IU College of Arts and Sciences Department of Biology professor Patricia L. Foster) found spontaneous mutation rates in E. coli DNA were actually three times lower than previously thought.
The new research appears in early edition of the journal Proceedings of the National Academy of Sciences.
The research points out that mismatch repair proteins
survey newly replicated DNA and detect mistakes.
This not only keep mutation rates low but may
also maintain the balance of guanine-cytosine
to adenine-thymine content in the genome.
Guanine-cytosine and adenine-thymine are the nitrogenous bases that bond between opposing DNA strands to form the rungs of the double helix ladder of DNA.
Foster: "We know that even in the absence of natural selection, evolution will proceed because new mutations get fixed at random in the genome.
So, if we want to determine whether specific patterns of evolutionary change are driven by [natural] selection, our knowledge of the expected pattern in the absence of selection is absolutely essential.
Here we are defining the rate and molecular spectrum of spontaneous mutations while minimizing the ability of natural selection to promote or eliminate mutations. This allows us to capture all mutations that do not cause the bacterium to die."
In a parallel experiment using a strain defective in mismatch repair, where the mutation rate was increased over 100-fold, researchers analyzed nearly 2,000 mutations and found they were strongly biased toward changing adenine-thymine base pairs to guanine-cytosine base pairs, the opposite of what is seen in normal bacteria.
The e. coli chromosome
"The molecular spectrum of spontaneous base-pair
substitutions in almost all organisms is dominated
by guanine-cytosine to adenine-thymine changes,
which tend to drive genomes toward higher
Because the guanine-cytosine content of genomes
varies widely, there must be some selective pressure,
or some non-adaptive mechanism, that can drive
genomes back toward increased
Patricia L. Foster, professor
Department of Biology
Indiana University College of Arts and Sciences
The new research*, demonstrates that mismatch repair is a major factor in the types of mutations that occur and in determining the base composition of the genome.
Because the activity of mismatch repair can be influenced by the environment, another implication of this work is that the pattern of mutations could be used in forensics to help determine where a particular bacterial strain originated.
Foster: "By establishing baseline parameters for the molecular nature of spontaneous mutational change, unbiased by selection, we can begin to achieve a deeper understanding of the factors that determine mutation rates, the mutational spectra, genomic base composition, how these may differ among organisms and how they may be shaped by environmental conditions.
Since mutations are the source of variation upon which natural selection acts, understanding the rate at which mutations occur and the molecular nature of spontaneous mutation changes leads us to a fuller understanding of evolution."
*Co-authored by IU Bloomington School of Informatics and Computing associate professor Haixu Tang, Informatics predoctoral researcher Heewook Lee and Department of Biology postdoctoral researcher Ellen Popodi.
The research took nearly two years to complete and was supported by a Multidisciplinary University Research Initiative Award from the U.S. Army Research Office.
Original article: http://www.eurekalert.org/pub_releases/2012-09/iu-nrp091712.php