Principles of Protein Structure - H. Schultz 1982

Protein Evolution
Detection of Distant Evolutionary Relationships
Conclusion

The vast Diversity of Proteins is a consequence of their evolution. Evolution has been driven by countless natural experiments—Mutations followed by Selection—which can be harnessed to study the principles of protein architecture. The primary mutational step in Introduction/18.html">Protein Evolution is the substitution of an amino acid residue; next in significance are the insertions and deletions of one or more residues, while massive alterations result from Gene Duplication and fusion.

Comparing known protein structures leads to several key Conclusions: Amino Acid Substitutions occur much more readily on protein surfaces than in the interior; functionally critical regions, such as active sites, are practically invariant, and so on. Furthermore, it has become evident that highly similar three-dimensional structures can be formed by entirely different Amino acid sequences. It is also important to highlight the exceptional conservation of chain folding, demonstrating that not only the final Structure, but the folding process itself, is subject to strong evolutionary selection. Additional structural insights can be gained by examining mutations that have not yet been shaped by selection, such as mutant human Hemoglobins. In this case, structural principles are uncovered through deviations from normal properties.

Two main trends can be identified in protein evolution: specialization and differentiation. Specialized proteins perform the same function across different organisms and can be used to trace organismal genealogy. However, it should be noted that protein specialization does not dictate the evolution of organisms. Protein Differentiation is the process that leads to the Functional diversity of homologous proteins. Thus, studying protein evolution not only deepens our understanding of structural Organization, but also reveals connections between proteins operating in completely different parts of a metabolic pathway. This helps bring a sense of order to the staggering array of existing proteins while simultaneously shedding light on the evolution of metabolic pathways. An important mechanism driving protein differentiation is gene duplication and fusion.

Much like divergent evolution (in homologous proteins), convergent evolution (in analogous proteins) occurs at all levels. For instance, functional convergence is a common phenomenon. Structural convergence may also occur, though this process remains difficult to trace given the Current state of knowledge. In particular, when investigating very distant evolutionary relationships, it is not always possible to distinguish between ANALOGOUS AND HOMOLOGOUS similarities.