Protein evolutionary considerations

A number of studies have been performed in the context of a theory that proteins and polynucleotides were formal in a suspension of proteinoid microspheres and the microspheres could then have evolved to contemporary cells. The experimental results and evolutionary considerations have been summarized in the textbook of Fox and Dose published in 1977 2). This review therefore deals with studies since 1977, although some description of literature before 1977 is reviewed as occasion demands. Since the evolutionary consideration of proteinoids and proteinoid micro-spheres has been discussed in much literature and many books, (e.g. 2, 3), the attention in this paper is focussed on the description of the biochemical and experimental parts of the literature. Inasmuch as protobiological activities of proteinoids in solution are carried into microspheres 2), experiments with proteinoids in solution are not excluded. 

The invalidity of the random heteropolymer model for proteins can also be understood from a more general point of view, since we know that protein sequences result from long evolution and are therefore, strictly speaking, not random. This consideration was the origin of a very productive approach that considers heteropolymer physics in connection with their evolution. This idea was not mentioned in any published work by I.M. Lifshitz. However, the authors of the present paper can witness that I.M. Lifshitz had evolutionary ideas on this subject and often discussed them. 

Identical amino acids are often inadequate to identify related proteins or, more importantly, to determine how closely related the proteins are on an evolutionary time scale. A more useful analysis includes a consideration of the chemical properties of substituted amino acids. When amino acid substitutions are found within a protein family, many of the differences may be conservative—that is, an amino acid residue is replaced by a residue having similar chemical properties. For example, a Glu residue may substitute in one family member for the Asp residue found in another both amino acids are negatively charged. Such a conservative substitution should logically garner a higher score in a sequence alignment than does a nonconservative substitution, such as the replacement of the Asp residue with a hydrophobic Phe residue. 

The bird lysozymes c, of which chicken egg white lysozyme (CL) is the most extensively studied example, provide an ideal system to recreate evolutionary intermediates and to study structure-function relationships of reconstructed ancestral proteins. Three major considerations qualify the avian lysozyme system for reconstruction of evolutionary pathways (1) the biochemistry of the enzymes has been extensively studied and well characterized,3,4 (2) there are many natural variants available from other birds, and homologous comparisons can be ensured since lysozymes for all game birds are encoded by a single gene,5 and (3) the three-dimensional structure of CL has been resolved at the atomic level, which allows for structural interpretation of the mutational impact.2,4 Proteins representing the ancestral, evolutionarily intermediate, and derived states of chicken and related bird lysozymes are made and characterized as described below. 

Only I amino acids are constituents of proteins. For almost all amino acids, the 1 isomer has S (rather than R) absolute configuration (Figure 3.5). Although considerable effort has gone into understanding why amino acids in proteins have this absolute configuration, no satisfactory explanation has been arrived at. It seems plausible that the selection of 1 over d was arbitrary but, once made, was fixed early in evolutionary history. 

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