This circle represents the Escherichia coli chromosome with 1,931 mutations. Blue lines represent base-pair substitutions and green lines represent the gain or loss of between one and four nucleotides.
Credit: Andrew J. Hanson, School of Informatics and Computing, Indiana University
The new research, which appears today in early editions of the journal Proceedings of the National Academy of Sciences, also notes that the mismatch repair proteins that survey newly replicated DNA and detect mistakes not only keep mutation rates low but may also maintain the balance of guanine-cytosine content 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.
"We know that even in the absence of natural selection, evolution will proceed because new mutations get fixed at random in the genome," Foster said. "So, if we want to determine whether specific patterns of evolutionary change are driven by selection, 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 eradicate mutations, which allows us to capture essentially all mutations that do not cause the bacterium to die."
The new research, 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, 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.
"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," Foster said. "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 mutational changes leads us to a fuller understanding of evolution."
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.
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