Principles of Protein Structure - G. Schultz 1982

Protein Evolution
Gene Fusion
Gene Fusion and Evolution

As has been established for certain Proteins, Gene Fusion played a critically important role in the course of evolution. Such historical evidence is preserved because, unlike V-C genes, a composite gene can also be incorporated into the germline. Cases of this kind have been uncovered through studies of Amino Acid and FATTY ACID Biosynthesis pathways. A classic example of a single polypeptide chain performing two enzymatic Functions is aspartokinase I–homoserine dehydrogenase of E. coli [578]. Comparative studies of Enzymes involved in Trp biosynthesis have revealed a striking diversity in the arrangement of multiple catalytic centers along the polypeptide chain [579], pointing to the possibility of both gene fusion and fission.

One of the most striking Examples is the fatty acid synthase of baker's Yeast [76, 580]. The gene contains two loci, fas1 and fas2, which encode two polypeptide chains yet harbor eight catalytic functions. There is no noticeable correlation between The sequence of biosynthetic reactions and the order of the corresponding functional domains along the two polypeptide chains. For instance, the coding order of domains in fas1 corresponds to biosynthetic steps 5, 6, 2, and 8.

Gene fusion does not result in drastic changes to protein properties.

* Fusion at the protein level is observed during the biogenesis of bacteriophage λ [142].

The first example of artificial gene-level fusion involved joining two enzymes participating in Histidine biosynthesis in Salmonella typhimurium [581]. This example demonstrates that gene fusion in itself does not cause drastic alterations in protein properties. Each of the two enzymes consists of two identical subunits, and this structural feature is preserved following gene fusion. Furthermore, the enzymatic and SPECTRAL PROPERTIES OF the individual proteins remain unchanged.

Fused proteins confer several advantages. First and foremost, functional domains are synthesized in stoichiometric amounts. A second advantage is the potential for favorable domain–domain interactions, which (unlike analogous interactions in Oligomeric Proteins) are independent of protein concentration [76]. Finally, in specialized biosynthetic pathways, the channeling of labile intermediates directly to the next enzyme can prove highly beneficial.

Gene fusion likely played a pivotal role in the evolution of Major Metabolic Pathways. The evolutionary trajectory of each of the enzymes listed below was probably shaped by combining a copy of an ancestral (di)nucleotide-binding domain with one or more distinct domains: phosphoglycerate kinase [235, 310, 311]; glyceraldehyde-3-phosphate, lactate, malate, and Alcohol dehydrogenases [91]; and Glycogen phosphorylase [236]. As discussed in Section 5.4, the (di)nucleotide-binding domain forms the N-terminal portion of the first four enzymes, whereas in Alcohol dehydrogenase it is located at the C-terminus, and in phosphorylase—in the middle of the chain. This indicates that constraints on spatial domain arrangement posed no barrier to their utilization as building blocks for constructing highly complex proteins during evolution.