Evolution molecular basis

McGeoch, D. J. and Davison A. J. (1995), Origins of DNA viruses , in A. J. Gibbs, C. H. Calisher and F. Garcia (Eds), Molecular Basis of Virus Evolution, Cambridge University Press, Cambridge,... 

The molecular basis of medium chain acyl-CoA dehydrogenase deficiency survey and evolution of 985A—G transition, and identification of five rare types of mutation within the medium chain acyl-CoA dehydrogenase gene. 

Comparative biochemistry. Some researchers believe that the proper role of comparative biochemistry is to put evolution on a molecular basis, and that detoxication enzymes, like other enzymes, are suitable subjects for study. Xenobiotic-metabolizing enzymes were probably essential in the early stages of animal evolution because secondary plant products, even those of low toxicity, are frequently lipophilic and as a consequence would, in the absence of such enzymes, accumulate in lipid membranes and lipid depots. The evolution of cytochrome P450 isoforms, with more than 2000 isoform cDNA sequences known, is proving a useful tool for the study of biochemical evolution. 

In this chapter, we will outline how evolutionary protein design methods are now being used to help uncover the molecular basis for temperature adaptation in enzymes. Before doing this, however, we will briefly review how temperature affects protein stability and enzyme activity. Then we will discuss some of the results of comparative studies of enzymes isolated from organisms adapted to different temperatures and the questions that can be addressed by laboratory evolution. 

Directed evolution and antibody affinity maturation offer efficient routes to redesigning proteins for new functional characteristics. Adaptive mutations and well-defined selection pressures allow structural analysis of the evolved products to provide insights into the molecular basis of protein structure and function. It is interesting to note that the majority of mutations that were obtained in the present maturation and directed evolution experiments were located at positions away from the enzymatic active sites. Perhaps this is due to the inherent difficulty in retaining catalytic activity with most active site amino acid substitutions. 

When the molecular basis of life was discovered, evolutionary thought began to be applied to molecules. As the number of professional research papers in this area expanded, a specialty journal, the Journal of Molecular Evolution, was set up. Established in 1971, JME is devoted exclusively to research aimed at explaining how life at the molecular level came to be. It is run by prominent figures in the field. Among the more than fifty people who make up the editorial staff and board, are about a dozen members... 

The chemist also wishes to relate samples in a similar manner. Can protein sequences from different animals be related and does this tell us about the molecular basis of evolution Can the chemical fingerprint of wines be related and does this tell us about the origins and taste of a particular wine Unsupervised pattern recognition employs a number of methods, primarily cluster analysis, to group different samples (or objects) using chemical measurements. 

The Kok model for 02 evolution is now generally accepted. However, this model does not address the molecular basis of the intermediates. Thus, the Kok model only provides a starting point from which more detailed mechanistic questions can be posed. 

The molecular basis for the evolution of distinct kdr mutations in different insects and arachnids remains unclear. Assuming that the pyrethroid binding site(s) (and/or the pyrethroid response domain) is composed of multiple amino acid residues, there are two ways by which different mutations can be selected in different insects and arachnids. First, the random mutation hypothesis mutation in any pyrethroid binding site/response domain affects pyrethroid toxicity without impacting normal sodium channel functional properties. Thus, selection of different mutations in different insects and arachnids is purely random. Second, the nonrandom mutation hypothesis mutation in any pyrethroid binding site/response domain affects pyrethroid toxicity, but some mutations also drastically alter normal sodium channel functional properties in one species, but not in another, presumably because of different sodium channel backbone sequences. That is, there may be severe fimess costs for some mutations, if placed out of their native protein context. 

Supramolecular chemistry is poised to make a big impact on numerous fields of science including molecular biology as well as chemistry. Complex structures that would be impossible to prepare in a stepwise fashion with covalent bonds are easily formed by the self-assembly process. The advances to date notwithstanding, there is much to learn about the molecular basis of self-organization. Given that one of the holy grails of chemistry is to unravel the processes of evolution and adaptation displayed by biological systems, it is clear that supramolecular chemists have their work cut out for them. 

Anfinsen, C. B. (1959). The Molecular Basis of Evolution. Wiley, New York. 

Anfinsen, Christian B. (1916-1991). An American biochemist who won the Nobel Prize for chemistry in 1972. His work involved the molecular basis of evolution and the chemistry of enzymes. He worked with Moore and Stein. His doctorate was granted from Harvard. 

Because the molecular basis of enantioselectivity is poorly understood, directed evolution seems to be an excellent choice for engineering enantioselective biocatalysts. Several impressive examples have been documented. In a classical study, Reetz and coworkers used error-prone PCR coupled with a 96-well plate based colorimetric screening method to increase the enantioselectivity of a Pseudomonas aeruginosa lipase toward 2-methyldecanoate. After several rounds of directed evolution, the enantioselectivity of the lipase increased from E = 1.04 (2% enantiomeric excess) to E = 25 (90-93% enantiomeric excess, ee) (E is the enantioselectivity factor). Using a similar approach. 

It has been proposed that the molecular basis for the evolution of H and M isozymes is that the M form is less susceptible to inhibition by pyruvate (36). This has been questioned since pyruvate levels in anaerobic muscle at 37° do not approach those required for inhibition (Table XXIII). Lactate levels do increase dramatically, and resistance to lactate inhibition has been suggested as an alternative explanation (267). 

The evolution of cytochrome c and protein molecules in general has been the subject of many papers and reviews, and can be treated relatively briefly here. The starting points must be Anfinson s Molecular Basis of Evolution (57), based on the early amino acid sequence work, and the discovery that same year by Kendrew and Perutz of the identity of three-dimensional folding of the related proteins myoglobin and hemoglobin (98,99). These illustrate the two components of any study of mac-romolecular evolution the chemical sequence of the polymer and the folding of the polymer in three dimensions. 

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