Principles of Protein Structure - G. Schultz 1982

Protein Evolution
Gene Fusion
The Gene Fusion Process

While Amino Acid Substitutions, insertions, and deletions represent relatively minor structural modifications during evolution, Gene Fusion triggers profound changes: it leads either to the joining of distinct polypeptide chains or to the duplication of a given chain.

In the past, the fusion of DNA Structural domains was apparently not a rare event. There is robust evidence indicating that gene fusions regularly occur during the ontogeny of modern organisms, such as at the stage preceding immunoglobulin synthesis.

The fusion of immunoglobulin V and C genes occurs at the DNA level. The light (L) chain of an immunoglobulin molecule consists of variable (V) and constant (C) regions (Fig. 4.2, c). The structural DNA regions encoding the V and C segments are located separately, yet on the same chromosome. Despite this Separation at the DNA level, it has been shown that the mRNA corresponding to the L chain represents a single continuous molecule [576]. The same is observed for heavy (H) chains, which consist of one V and three C regions [477]. Moreover, experiments using labeled Amino Acids revealed only a single growing point during L-chain synthesis, indicating the absence of V- and C-chain joining at the protein level*. In Hybridization experiments using L-chain mRNA as a probe, DNA rearrangement was observed in precursor Cells producing IMMUNOGLOBULINS [577]. This latter fact demonstrates that the fusion of V and C regions occurs exclusively at the DNA level rather than at the RNA level. This issue, however, remains not yet fully resolved [78].

The fusion of different DNA chains is also common in lysogenic Bacteriophages, which inject their DNA into the bacterial genome, where it remains dormant for some time. It should also be noted that DNA splicing is a fundamental step in all Introduction/32.html">Genetic Engineering experiments [542, 575].