Principles of Protein Structure - H. Schulz 1982

Protein Evolution

Biology is a natural science with deep historical roots. All existing biological species have gradually evolved from a single ancestor or a very limited number of precursors. Since chance may have played a significant role in past events, we must accept the fact that evolutionary pathways can probably never be fully explained in terms of "cause and effect." For researchers inclined to build elegant systems based on The Development of certain General Principles, this poses a major obstacle. However, this quasi-random development has yielded a vast diversity of biological species, which can be viewed as the outcome of countless natural experiments. We should appreciate these experiments and strive to analyze and interpret their results.

Introduction/18.html">Protein Evolution involves the substitution of individual residues, the insertion and deletion of several residues, as well as Gene Duplication and fusion. For Proteins, the principal milestones of the historical* process are marked by Amino Acid Substitutions within the polypeptide chain. Over time, these substitutions accumulate, eventually erasing any resemblance between the initial** and final Amino acid sequences. Generally, however, even after the sequence similarity between two homologous proteins has vanished, the correspondence in their chain folding remains preserved. The propensity for substitutions varies noticeably among residues at different positions within the chain (Fig. 7.1, b). The Differences between homologous proteins are not restricted to single amino acid replacements. More substantial events include the insertions and losses (gaps, deletions) of individual residues or entire groups of residues (Fig. 7.1, a). The presence of such insertions and deletions greatly complicates the sequence alignment of distantly related proteins [803].

* When using the term "history," we usually refer to somehow recorded events. In this context, applying these concepts to proteins means that we regard nucleotide and amino acid sequences as a record of past events.

** It should be noted that we only know The Structure of currently existing proteins. Therefore, we can judge evolutionary Changes in the past solely by examining the differences observed among homologous proteins.

Knowledge of three-dimensional protein structures provides invaluable assistance in such cases. Current data indicate that residues located in the interior of a protein are generally less susceptible to change, and that all differences between homologous proteins (amino acid substitutions, deletions, or loop insertions in the chain) are confined to the molecular surface. Consequently, the sequences of distantly related Proteins can be aligned based on residues occupying geometrically equivalent positions in their Spatial Structure.

Profound changes are associated with gene duplication, which can lead to a doubling of the polypeptide chain length. Furthermore, instances of the fusion of different structural genes are known, indicating the translocation of one or more genes to a new genomic locus.

Homologous proteins arise through specialization or differentiation. The comparison of homologous proteins reveals certain general patterns in protein architecture [250], and, as already noted, studying protein evolution helps resolve many general biological problems. In this regard, it is useful to distinguish between protein specialization and differentiation [473]. Specialization refers to the evolution of homologous proteins that perform the same function in different organisms. Conversely, Protein Differentiation is the process leading to the functional diversification of homologous proteins, frequently within a single Organism.

The investigation of protein specialization makes it possible to establish the genealogy of organisms. As a rule, the Amino Acid Sequence and the folding pattern are conserved so well during evolution that proteins from even genetically distant organisms retain a distinct resemblance. Thus, by studying protein specialization, one can reconstruct genealogy—that is, the origin and evolutionary relationships of organisms. Therefore, Phylogenetic Analysis based on protein specialization can be regarded as a powerful tool in Taxonomy.

Protein differentiation reflects the evolution of biochemical pathways. Studies focusing on protein differentiation pursue different goals. In this case, structural similarity often reveals unexpected biological connections, which can then be utilized, for instance, to trace the evolution of METABOLISM. Moreover, differentiation compellingly demonstrates that biological diversity is constrained and that, in this respect, proteins can be classified into distinct groups [474]. A classic example of a Class of proteins generated by differentiation is the family of Serine proteases (Table 9.4), which regulate A wide variety of vital processes in The Human Body.

Hence, it is evident how immense The Significance of molecular-level Cell/13.html">Protein Structure analysis will be for Pathophysiology and pharmacology [602].