Abstract
Previously, it was proposed that protein receptors evolved from self-binding peptides that were encoded by self-interacting gene segments (inverted repeats) widely dispersed in the genome. In addition, self-association of the peptides was thought to be mediated by regions of amino acid sequence similarity. To extend these ideas, special features of receptors have been explored, such as their degree of homology to other proteins, and the arrangement of their genes for clues about their evolutionary origins and dynamics in the genome. As predicted, BLASTP searches for homologous proteins detected a greater number of unique hits for queries with receptor sequences than for sequences of randomly-selected, non-receptor proteins. This suggested that the building blocks (cohesion modules) for receptors were duplicated, dispersed, and maintained in the genome, due to structure/function relationships discussed here. Furthermore, the genes coding for a representative panel of receptors participated in a larger number of gene–gene interactions than for randomly-selected genes. This could conceivably reflect a greater evolutionary conservation of the receptor genes, with their more extensive integration into networks along with inherent properties of the genes themselves. In support of the latter possibility, some receptor genes were located in active areas of adaptive gene relocation/amalgamation to form functional blocks of related genes. It is suggested that adaptive relocation might allow for their joint regulation by common promoters and enhancers, and affect local chromatin structural domains to facilitate or repress gene expression. Speculation is included about the nature of the coordinated communication between receptors and the genes that encode them.
Highlights
Ligand–receptor interactions are essential for life and mediate intercellular communication, hormone signaling, neurotransmission, immune function, metabolic processes, and more
This study focused on finding distant homologs of receptor sequences and was not aimed at finding protein–protein interactions, per se
Some of the cohesion modules assembled into more complex domain structures that evolved into receptors, while the original self-binding module retained its ligand function
Summary
Ligand–receptor interactions are essential for life and mediate intercellular communication, hormone signaling, neurotransmission, immune function, metabolic processes, and more. According to the self-associating peptide theory, self-binding peptides were encoded in the proto-genome by self-binding nucleotide sequences (inverted repeats) that were mobile (transposable) and extensively duplicated (see Figure 1). These transposable exons assembled into more complex, modular protein structures that eventually diverged and evolved into ligands and receptors that retained and refined the initial self-affinity of their ancestral peptides. Ligand–receptor interactions may have originally been based on areas of amino acid sequence homology (dimer to ‘heterodimer’ transition [1]), this system was likely adapted to include complementarity as an additional mode of recognition, as
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