Selection Of Advantageous Mutations Research Articles

MUTATIONS IN radA ARE RESPONSIBLE FOR ACQUIRED RADIO-RESISTANCE IN AN Escherichia coli STRAIN

When bacteria are exposed to chronic or cyclic irradiation with ultraviolet (UV) light, it is observed that their resistance to this agent is increased by the selection of advantageous mutations under those conditions. UV light produces different damages in DNA, the repair of which is necessary to maintain the integrity of the genome. However, some damages can lead to such mutations when they are not properly repaired. In an earlier work, five subcultures of a wild-type Escherichia coli strain (PQ30) were cyclically irradiated with UV and different strains resistant to UV light and gamma radiation were obtained. In a preliminary mapping, different genes involved in their resistance to radiation were identified. In one of these strains, designated as IN801, the radA gene, the product of which is involved in recombinational DNA repair, was identified. In this work, cells from another wild-type strain (AB1157) were transformed with a plasmid (pUC19) that carries the radA gene from either PQ30 or IN801, in order to establish whether the radio-resistant phenotype can be transferred to a normal strain. Only cells that received the IN801 radA gene showed increased resistance to UV and gamma radiation. Further radA sequencing showed that the gene of IN801 acquired two-point mutations that replace two amino acids in the RadA protein, which most likely changed its enzymatic activities. These results confirm that radA participates in the radiation resistance of IN801.

Evolutionary thrift: mycobacteria repurpose plasmid diversity during adaptation of type VII secretion systems

Mycobacteria have a distinct secretion system, termed type VII (T7SS), which is encoded by paralogous chromosomal loci (ESX) and associated with pathogenesis, conjugation, and metal homeostasis. Evolution of paralogous gene families is of interest because duplication is an important mechanism by which novel genes evolve, but there are potential conflicts between adaptive forces that stabilize duplications and those that enable evolution of new functions. Our objective was to delineate the adaptive forces underlying diversification of T7SS. Plasmid-borne ESX were described recently, and we found evidence that the initial duplication and divergence of ESX systems occurred on plasmids and was driven by selection for advantageous mutations. Plasmid conjugation has been linked to T7SS and type IV secretion systems (T4SS) in mycobacteria, and we discovered that T7SS and T4SS genes evolved in concert on the plasmids. We hypothesize that differentiation of plasmid ESX helps to prevent conjugation among cells harboring incompatible plasmids. Plasmid ESX appear to have been repurposed following migration to the chromosome, and there is evidence of positive selection driving further differentiation of chromosomal ESX. We hypothesize that ESX loci were initially stabilized on the chromosome by mediating their own transfer. These results emphasize the diverse adaptive paths underlying evolution of novelty, which in this case involved plasmid duplications, selection for advantageous mutations in the mobile and core genomes, migration of the loci between plasmids and chromosomes, and lateral transfer among chromosomes. We discuss further implications for the choice of model organism to study ESX functions in Mycobacterium tuberculosis.

Just like the rest of evolution in Mother Nature, the evolution of cancers may be driven by natural selection, and not by haphazard mutations.

Sporadic carcinogenesis starts from immortalization of a differentiated somatic cell or an organ-specific stem cell. The immortalized cell incepts a new or quasinew organism that lives like a parasite in the patient and usually proceeds to progressive simplification, constantly engendering intermediate organisms that are simpler than normal cells. Like organismal evolution in Mother Nature, this cellular simplification is a process of Darwinian selection of those mutations with growth- or survival-advantages, from numerous ones that occur randomly and stochastically. Therefore, functional gain of growth- or survival-sustaining oncogenes and functional loss of differentiation-sustaining tumor suppressor genes, which are hallmarks of cancer cells and contribute to phenotypes of greater malignancy, are not drivers of carcinogenesis but are results from natural selection of advantageous mutations. Besides this mutation-load dependent survival mechanism that is evolutionarily low and of an asexual nature, cancer cells may also use cell fusion for survival, which is an evolutionarily-higher mechanism and is of a sexual nature. Assigning oncogenes or tumor suppressor genes or their mutants as drivers to induce cancer in animals may somewhat coerce them to create man-made oncogenic pathways that may not really be a course of sporadic cancer formations in the human.

Deep sequencing reveals persistence of intra- and inter-host genetic diversity in natural and greenhouse populations of zucchini yellow mosaic virus

The genetic diversity present in populations of RNA viruses is likely to be strongly modulated by aspects of their life history, including mode of transmission. However, how transmission mode shapes patterns of intra- and inter-host genetic diversity, particularly when acting in combination with de novo mutation, population bottlenecks and the selection of advantageous mutations, is poorly understood. To address these issues, this study performed ultradeep sequencing of zucchini yellow mosaic virus in a wild gourd, Cucurbita pepo ssp. texana, under two infection conditions: aphid vectored and mechanically inoculated, achieving a mean coverage of approximately 10 ,000×. It was shown that mutations persisted during inter-host transmission events in both the aphid vectored and mechanically inoculated populations, suggesting that the vector-imposed transmission bottleneck is not as extreme as previously supposed. Similarly, mutations were found to persist within individual hosts, arguing against strong systemic bottlenecks. Strikingly, mutations were seen to go to fixation in the aphid-vectored plants, suggestive of a major fitness advantage, but remained at low frequency in the mechanically inoculated plants. Overall, this study highlights the utility of ultradeep sequencing in providing high-resolution data capable of revealing the nature of virus evolution, particularly as the full spectrum of genetic diversity within a population may not be uncovered without sequence coverage of at least 2500-fold.

Molecular Prognosticators and Genomic Instability in Papillary Thyroid Cancer

Tumor progression has been attributed to the accumulation of DNA damage concurrent with selection of advantageous mutations; this DNA damage may result from failure to maintain genomic integrity or from susceptibility to carcinogens. Glutathione S-transferases (GSTs), enzymes that metabolize many carcinogens, may play a role in preserving genome integrity. The objectives of this study are to assess the relationship of GST genotypes with prognosis, clinicopathologic parameters, and genomic instability in papillary thyroid cancer. Prospective analysis. GSTM1 and GSTT1 genotypes of 35 matched normal and papillary thyroid cancer specimens were determined by polymerase chain reaction (PCR) using primers specific for the coding sequences of each gene. Genomic instability was measured by intersimple sequence repeat PCR for each tumor/normal pair and compared with the GAMES prognostic scoring system and clinicopathologic parameters including age, extrathyroidal extension, tumor grade, size, stage metastasis, sex, and smoking history. GSTM1 and GSTT1 null genotypes were found in the normal tissues of 46% and 45%, respectively. No gene losses were detected in the tumor specimens. A significant association between the GSTM1 null genotype and increased risk of recurrence and death was observed. Elevated GII correlated with smoking and tumor stage but not with GST genotype. The association of GSTM1 null genotype with intermediate and high risk GAMES categories suggests that GSTM1 provides some protection against disease progression. However, this protection does not confer resistance to disease onset. GST genotyping may be a useful adjunct prognosticator with GAMES.

Positive selection scanning of parasite DNA sequences.

Parasites successfully exist within the host as a result of highly specific genetic adaptations. Therefore, detecting genes that contain relevant adaptive mutations can provide a guide to biological processes that are potentially essential to the parasite. Random genetic mutations that confer selective advantage can act to alter amino acids so as to confer gain of function that has positive impact on the survival of the parasite. Directional selection of advantageous mutations results from an elevated rate of nonsynonymous substitutions in rapidly evolving genes. Genes on which this positive selection operates are considered to have an evolutionary characteristic such that the normalized number of nonsynonymous (dn) substitutions is greater than that of synonymous (ds) substitutions. By searching in a statistically robust way for genes that contain this characteristic, it is possible to apply a stringent method to identify genes that may be under positive selection and thus to identify biological processes involving those genes that are essential to the survival of the parasite. Genes detected typically class into those under host immune surveillance and those intrinsic to pathways essential to survival of the parasite within the host. Depending on their function and location of protein expression, such genes have the potential to provide exceptional vaccine and drug candidates.

Genetic diversity in Leavenworthia populations with different inbreeding levels.

Levels of neutral genetic diversity within and between populations were compared between outcrossing (self-incompatible) and inbreeding populations in the annual plant genus Leavenworthia. Two taxonomically independent comparisons are possible, since self-incompatibility has been lost twice in the group of species studied. Within inbred populations of L.uniflora and L.crassa, no DNA sequence variants were seen among the alleles sampled, but high diversity was seen in alleles from populations of the outcrosser L. stylosa, and in self-incompatible L. crassa populations. Diversity between populations was seen in all species. Although total diversity values were lower in the sets of inbreeding populations, between-population values were as high or higher, than those in the outcrossing taxa. Possible reasons for these diversity patterns are discussed. As the effect of inbreeding appears to be a greater than twofold reduction in diversity, we argue that some process such as selection for advantageous mutations, or against deleterious mutations, or bottlenecks occurring predominantly in the inbreeders, appears necessary to account for the findings. If selection for advantageous mutations is responsible, it appears that it must be some form of local adaptive selection, rather than substitution of alleles that are advantageous throughout the species. This is consistent with the finding of high between-population diversity in the inbreeding taxa.