ASSEMBLY OF EXONS FROM UNITARY TRANSPOSABLE GENETIC ELEMENTS - IMPLICATIONS FOR THE EVOLUTION OF PROTEIN-PROTEIN INTERACTIONS

The discovery of ''genes-in-pieces'' provided the first evidence that modern proteins evolved through the assembly and shuffling of simpler building blocks-generally equated with exons. In the theoretical model presented here, it is suggested that exons were created from even sma ller modules that have been termed duplication units. Furthermore, the se segments may represent the ultimate building blocks for protein ass embly. The nucleotide sequences of the duplication units appear to res emble those of mobile genetic elements such as transposons or insertio n sequences, i.e. they possess direct repeats at each end and inverted sequences extending 15-25 base pairs from these direct repeats. Durin g evolution, these transposable exons (trexons) would have been replic ated and dispersed in the genome thereby promoting homologous recombin ation and further duplication. Thus, the transposition and splicing of these gene segments gave rise to increasingly complex proteins as wel l as multi-gene families of proteins. It has been proposed that peptid es encoded by the first trexons were predisposed to form dimers or oli gomers. Detailed structural analysis of various protein-protein comple xes has revealed a tendency for the duplication units to self-associat e. Self-binding peptides could have ultimately led to the evolution of protein ligands and receptors with high affinity. (C) 1998 Academic P ress.