Peptide hormone and receptor evolution

• An important and fascinating theme that unifies both invertebrate and vertebrate endocrinologists is that of the evolution of peptide precursor and receptor genes. Peptide signalling plays a crucial role in processes that control decisive physiological events in organisms as divergent as yeast and mammals. The majority of small neuronal/endocrine peptides exert their functions via an interaction with heptahelical membrane receptors belonging to the G protein-coupled receptor superfamily, a large and diverse signal transducing protein category which has very ancient evolutionary roots. Most of the larger peptides and growth factors function via other well-conserved receptor classes that contain only a single transmembrane segment. The symposium on peptide hormone and receptor evolution brought together scientists studying peptide–receptor evolution in widely divergent metazoans. Two State-of-the-Art lectures gave overviews of current knowledge of peptide and receptor gene evolution. The sequencing and annotation of entire animal genomes constitutes a very exciting development that have already revolutionized the general views on metazoan macroevolution. The resulting burst of molecular data represents an impressive boost of novel opportunities for comparative and functional genomics research. Several vertebrate peptide and receptor families were described by Dan Larhammar to have multiplied in the 1–2 basal vertebrate tetraploidizations and in a third tetraploidization in ray-finned fishes before the radiation of teleosts. Families proposed to have multiplied in these events include NPY, tachykinins, opioid peptides, as well as the receptors for these three peptide families. The dynamics of coevolutionary change were discussed by Jozef Vanden Broeck based on several examples of peptide–receptor partners that show conservation across the protostomian–deuterostomian barrier. These examples include peptides belonging to the NPY, tachykinin, glycoprotein hormone and insulin-related peptide families, and their respective receptors. Additional examples of coevolution between peptides and their corresponding receptors in insects (the mosquito Aedes aegypti) and chelicerates (the tick Boophilus microplus) were presented by Ron Nachman. His detailed analysis of peptide receptor pharmacology has led to the production and selection of peptidomimetic compounds which specifically activate a particular receptor, while showing enhanced resistance against peptidases. This type of work may ultimately lead to the creation of novel, environmentally safe pest agents for insect management. In two other presentations, the evolution of two quite complex vertebrate peptide receptor systems were discussed. The five divergent and presumably ancient melanocortin receptors found in mammals have only three orthologues in the two sharks investigated so far (Angela Baron). Both the ά-MSH receptor MC1 and the ACTH receptor MC2 still remain to be identified or may have been lost or become widely divergent. The evolution of the large VIP/PACAP/secretin family (Florbela Vieira) involves duplicate PACAP genes in teleost fishes, whereas only a single VIP gene seems to exist. The PACAP gene and its chromosomal environment is more strongly conserved than the VIP gene. Invertebrates only have a single member most closely resembling PACAP. The concluding discussion largely revolved around the proposed tetraploidizations in early vertebrate evolution. While some hesitation still lingers, there is nevertheless no alternative explanation that can account better than the chromosome duplication (and tetraploidization) scenario for the extensive chromosome similarities and the high number of gene duplications that arose before gnathostomatous radiation. Additional gene duplications in early vertebrates were mentioned leading to the somatostatin 2-urotensin II gene pair and the somatostain 1-urotensin II-related peptide gene pair (Hervé Tostivint). Also the possible orthology relationships between peptides described in invertebrates, particularly insects, and vertebrates were discussed. Undoubtedly, definitive orthology relationships of neuropeptide precursor genes between protostomes and deuterostomes are often difficult to determine from sequence comparisons only, and will hopefully be aided by information on chromosome locations and gene neighbours.

Keyword

Animals

Conserved Sequence

Evolution; Molecular

Gene Duplication

Humans

Peptide Hormones/*genetics

Receptors; Neuropeptide/*genetics

Structure-Activity Relationship

MEDICINE

MEDICIN

Publication and Content Type

ref (subject category)

art (subject category)