How well do we understand DNA?

Hi TheLit,Too bad about the other thread, but feel free to start a new topic with whatever questions or comments you might have. I probably won't start one unless you indicate you're interested in continuing the island biogeography discussion or have any questions concerning endosymbiosis, etc.I would, however like to add a little bit to WK's explanation above. An interesting area of active research involves the "evolution of evolvability". IOW, there are indications in some organisms that high mutation rates in certain segments of the genome are actually adaptive. There's an excellent review article available on-line by Metzgar and Wills (full citation: Cell, Vol. 101, 581—584, June 9, 2000) called Evidence for the Adaptive Evolution of Mutation Rates that discusses the theoretical and logical basis for why this concept makes sense. Although the technical details may get a bit beyond where you're at currently, the general discussion should be accessible and understandable. Let me know if you have any questions on the article or its conclusions.In addition, hypervariability has been studied in certain organisms, including yeast and cone shells, that show what appears to be an adaptive (i.e. selective advantage) for increasing mutation rates to produce large degrees of variability in these organisms. For example, Conticello SG, Gilad Y, Avidan N, Ben-Asher E, Levy Z, and Fainzilber M, 2001, "Mechanisms for Evolving Hypervariability: The Case of Conopeptides", Mol. Biol. Evol. 18:120—131.

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Hypervariability is a prominent feature of large gene families that mediate interactions between organisms, such as venom-derived toxins or immunoglobulins. In order to study mechanisms for evolution of hypervariability, we examined an EST-generated assemblage of 170 distinct conopeptide sequences from the venoms of five species of marine Conus snails. These sequences were assigned to eight gene families, defined by conserved elements in the signal domain and untranslated regions. Order-of-magnitude differences were observed in the expression levels of individual conopeptides, with five to seven transcripts typically comprising over 50% of the sequenced clones in a given species. The conopeptide precursor alignments revealed four striking features peculiar to the mature peptide domain: (1) an accelerated rate of nucleotide substitution, (2) a bias for transversions over transitions in nucleotide substitutions, (3) a position-specific conservation of cysteine codons within the hypervariable region, and (4) a preponderance of nonsynonymous substitutions over synonymous substitutions. We propose that the first three observations argue for a mutator mechanism targeted to mature domains in conopeptide genes, combining a protective activity specific for cysteine codons and a mutagenic polymerase that exhibits transversion bias, such as DNA polymerase V. The high Dn/Ds ratio is consistent with positive or diversifying selection, and further analyses by intraspecific/interspecific gene tree contingency tests weakly support recent diversifying selection in the evolution of conopeptides. Since only the most highly expressed transcripts segregate in gene trees according to the feeding specificity of the species, diversifying selection might be acting primarily on these sequences. The combination of a targeted mutator mechanism to generate high variability with the subsequent action of diversifying selection on highly expressed variants might explain both the hypervariability of conopeptides and the large number of unique sequences per species.

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Although again the details are technical, the conclusion is that a high degree of variability provides a distinct selective advantage to this organism, and hence elevated mutation rates, rather than being a negative for the species, is actually a benefit (in this case the production of toxins this predator uses).

Hi, TheLit. In a manner of speaking, you're correct. There are areas of the genome that are known as mutational hotspots, or hypervariable regions. Although the mutations are random (as always), these regions are more likely statistically to have mutations occur. I highly recommend Lynn Caporale's quite accessible book, "Darwin in the Genome" for a very detailed discussion. The journal articles I mentioned in my last post show how such hypervariability can serve an adaptive function - in other words can be selected for by natural selection. It's more complicated than this, of course, but this is the short version. The obverse of the hypervariable coin are regions that are highly resistant to mutation - we call them "highly conserved". Most of these highly conserved regions are areas where change of any kind - even small changes - have nearly universally fatal effects either for the cell or for the organism itself. So here too you are mostly correct.However, what you mention isn't really the main problem faced when classifying clonal organisms in general and bacteria in particular. Obviously, the biological species concept falls apart when you are dealing with organisms that not only don't have sex but can actually swap genes across kingdoms! Any mutation that occurs in one bacteria (assuming it is adaptive rather than fatal) will create an entire new clonal lineage - instant "species" if you will (although some bacterial lateral transfers would be the equivalent of giving a mouse functional wings in one generation). Selection operating on one of the new clonal lineages make create "gaps" between bundles of closely related but genetically different clones. Biologists thus use a "typological species concept" when classifying them, which basically classifies "strains" by degree of relatedness. So E. coli might be a nice name for a large bundle of clone lineages that share common typology, but the folks that work with them will qualify that nomenclature with a type name as well. The type may simply be a number, or it may be an alphanumeric string identifying a particular, well studied and carefully screened strain.More info than you probably wanted, of course. This message has been edited by Quetzal, 02-03-2005 23:03 AM