At each step, a sample of the population of molecules was sequenced and the changes in the population composition were monitored.
Genes, Enzymes, and Populations
During the discussion, it became clear that this trait is equivalent to the fitness. The discussion focused first on figure 1 and the accumulation of genetic variation in the population of ribozymes. The average number of mutations per molecule seems slightly higher in line B formamide than in line A in all generations, whereas the number of mutable positions is higher in line A 35 than in line B No significant difference exists between the average active fraction in generation 1 and the average active fraction generation However, there is a clear decrease between generation 1 and generation 4 and then an increase towards initial levels from generation 4 and generation 10 in both lines.
We speculated about this pattern without reaching a clear conclusion:.
When ribozyme molecules from the initial population and from the generation 10 of lines A and B are selected on a new substrate RNA with a phosphorothioate bond , the adaptation of lines having accumulated mutations New-A and New-B was much faster than the initial homogenous wild type population New-wild-type fig. Importantly, most of these genetic variants were confirmed to be cryptic in the sense that they do not affect or affect negatively the activity of the ribozyme in the presence of the initial RNA substrate.
The scenario suggested by the authors is the following:. Thus, populations containing cryptic genetic variation have a clear selective advantage under changing environments. The Azo D genotype crystallized an interesting part of the discussion, as it is a variant that, although inactive on the new substrate, could become the dominant variant in one of the populations line New-A during the step 2 of the experiment. This could be interpreted as a form of molecular parasitism or commensalism or less likely mutualism.
If Azo D needs a partner to perform the reaction and prevents its partner from performing it itself or competes with it for the substrate , it would be a form of parasitism. If Azo D needs a partner to perform the reaction and does not prevent its partner from performing it itself or, better, uses a partner that has already reacted , it would be a form of commensalism.
Analysis of the evolution of the population of ribozymes under the new selective conditions. Sequence data of samples from all the experimental steps made it possible to study the genetic evolution of the population of ribozymes, in particular during the second step of the experiment. To facilitate representation and visualization, a subset of the data generations 1, 4 and 8 of the new lines were analyzed by principal component analysis PCA.
We discussed the procedure itself: on the basis of a multiple alignment of all sequence data to be analyzed all 3 or maybe 8 generations together , each individual ribozyme molecule was first reduced to a vector of 5 possible values gap or one of the 4 nucleotides ; PCA was performed on this data and the position of each molecule in the multidimensional space of genotypes was projected into the two dimensions maximizing information, resulting in fig.
The fig. We discussed in particular the following elements:. The Azo D genotype forms a group separated from the main New-A population along the second principal component axe with very little intermediate forms possible disruptive selection. My point is that variation cannot be caused by robustness if you understand these three words in their usual sense. One could meaningfully say that cryptic genetic variation is authorized or allowed by robustness of phenotypes to mutations or that cryptic genetic variation is caused by mutation assuming the robustness of the phenotype.
But the sentence as it is written either contains a semantic mistake or is a meaningful paradox, in which case my natural reluctance to follow self-citation references note 1 entirely accounts for my confusion….
But I agree that the protocol used by the author should by and large enrich the population for cryptic variation. As hard as I tried, I could not reconcile the data presented in the figure 1a and the supplementary figure 5. The initial decrease G1 to G4 and following increase G4 to G10 in the active fraction of ribozymes over selection rounds is clear in figure 1a. As the selection conditions do not change from G1 to G10, the pattern has to be explained by accumulation or loss of specific genetic variation in the population of molecules. I was expecting to see something happening around generation 4 in the graphs representing the fraction of molecules in the population with a mutation at a specific nucleotide as a function of time selection rounds sup.
My logics is most probably faulty, but I do not see where; if you find out, please tell me. I wonder what would come out of a repetition of the step 2 with the same three molecular populations but in the presence of the initial RNA substrate. Other studies have demonstrated that CYP2J2 is the major enzyme responsible for the metabolism of many different drugs. Wu et al proved that CYP2J2 is an important enzyme for the pharmacokinetics of anthelmintics in human liver.
Christina Westphal demonstrated that the overexpression of CYP2J2 is a protective factor against arrhythmia susceptibility in a mouse model of cardiac hypertrophy.
Genes, Enzymes, and Populations | Adrian Srb | Springer
We also identified the polymorphisms of CYP2J2 and their genetic frequencies in a Tibetan population. It is necessary to carry a more in-depth study for exploring the distribution of the polymorphisms and their effect on drug clearance rates and adverse drug reactions. In conclusion, we systematically analyzed the variants of CYP2J2 by directly sequencing the gene in a Tibetan population and compared its distribution in other ethnic groups. The study offers some useful information for the establishment of a database of Tibetan population CYP2J2 genetic polymorphisms, which would offer a theoretical basis for individualized medical treatment and drug genomics studies in Tibet.
We need a larger sample size for validating our study, which would be useful for the advancement of personalized medicine. Conceptualization: Peilong Cao. Data curation: Qian Zhao. Formal analysis: Yuan Shao. Methodology: Qian Zhao, Hua Yang. Project administration: Baiya Li. Resources: Yuan Shao, Honghui Li.
Software: Tianbo Jin. Validation: Baiya Li. Writing — original draft: Peilong Cao. CYP2J2 ; drug metabolism ; gene polymorphism ; Tibetan. You may be trying to access this site from a secured browser on the server. Please enable scripts and reload this page.
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Separate multiple e-mails with a ;. Thought you might appreciate this item s I saw at Medicine. Send a copy to your email. Some error has occurred while processing your request.
Please try after some time. PC and QZ have equally contributed to this work. The authors have no funding and conflicts of interest to disclose. Received January 5, Accepted September 5, Abstract 1 Introduction 2 Materials and methods 2. Back to Top Article Outline. Table 1. Table 2.
- Genes, Enzymes, and Populations;
- Genetic variation;
- Enzyme variants in human populations..
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Table 3. Table 4. Figure 1. Figure 2.
The influence of cytochrome P pharmacogenetics on disposition of common antidepressant and antipsychotic medications. Clin Biochem Rev ;— Cited Here Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab Dispos ;— PubMed CrossRef. Molecular cloning and expression of CYP2J2 , a human cytochrome P arachidonic acid epoxygenase highly expressed in heart. J Biol Chem ;—8.
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