Phylogenetic relationships and chromosomal location of five distinct glycine receptor subunit genes in the teleost Danio rerio

Glycine receptors mediating synaptic inhibition are heteromeric proteins co nstituted of alpha and beta subunits. The mammalian GlyR subunits constitut e a subgroup in the superfamily of ligand-gated ionic channels. To compare the evolutionary events in the mammalian and teleostean lineages for the re ceptor family, we first undertook systematic cloning of the constitutive su bunits of the zebrafish glycine receptor. The isolation of two alpha subuni ts (alpha Z1 and alpha Z2) and one beta subunit (betaZ) has been reported p reviously and we report here the characterization of two novel alpha subuni ts, alpha Z3 and alpha Z4, increasing the known zebrafish subunits number t o four alpha and one beta. Establishment of phylogenetic relationships reve als that alpha Z1, alpha Z3 and betaZ are orthologous to mammalian alpha1, alpha3 and beta subunits. However, two zebrafish GlyR alpha subunit genes a re orthologous to the unique avian and mammalian alpha4 subunit revealing a duplication of the alpha4 gene in zebrafish. Whole-mount in situ hybridiza tion in 24-hours post fertilization (hpf) and 52-hpf embryos of the daughte r gene products display very different expression patterns indicating disti nct functions of the duplicated genes. Gene mapping reveals that the two du plicated genes are localized on two different linkage groups (LG5 and LG22) as would be daughter genes resulting from a large-scale duplication of the ancestral genome. Finally, we report that a linked pair of genes on human chromosome 4 (alpha3 and beta) is also linked on linkage group 1 in zebrafi sh (alpha Z3 and betaZ) as a consequence of a mosaic conserved syntheny.