A mammalian homologue of the Drosophila retinal degeneration B gene: implications for the evolution of phototransduction mechanisms

Abstract

Comparative analysis of homologous genes in distantly related species provides important insights into the evolution of complex physiological processes. The Drosophila retinal degeneration B (rdgB) gene encodes a protein involved in phototransduction in the fly. We have isolated a human gene, DRES9, and its murine homologue (Dres9), which show a high degree of similarity to the Drosophila rdgB gene. RNA in situ hybridization studies performed on mouse-embryo tissue sections at various developmental stages revealed that Dres9 is expressed at very high levels in the neural retina and in the central nervous system (CNS), similar to its Drosophila counterpart. The high level of sequence conservation and similarities in the expression patterns of rdgB and DRES9 during development in Drosophila and mammals indicate that Dres9 is the orthologue of RdgB, and strongly suggest a possible functional conservation of these proteins during evolution. DRES9 encodes a phosphatidylinositol-transfer protein, suggesting that phosphatidylinositol may have a role as an intracellular messenger in vertebrate phototransduction. The identification of this gene and the study of its expression pattern in mammals will help shed new light on the evolution of vision mechanisms and suggest DRES9 as a candidate gene for human retinopathies.

Chromosomal localization, genomic organization and evolution of the genes encoding human phosphatidylinositol transfer protein membrane-associated (PITPNM) 1, 2 and 3

“…A combination of genetic, bio-chemical and electrophysiological studies has provided evidence that rdgB plays a critical role in the phospholipase Cdependent phototransduction cascade in flies. The demonstration that the murine PITPNM1 is able to correct the visual defect in rdgB defective flies (Chang et al, 1997) and that all three genes are highly expressed in the mammalian retina (Aikawa et al, 1997;Chang et al, 1997;Guo and Yu, 1997;Rubboli et al, 1997;Lev et al, 1999;Lu et al, 1999) suggests that there may be similarities between the invertebrate and vertebrate phototransduction pathways not previously appreciated. Such evidence makes the three PITPNM genes attractive candidates for human eye disease.…”

“…Originally, only a single membrane-spanning mammalian gene homologous to the Drosophila rdgB gene was described (Aikawa et al, 1997;Chang et al, 1997;Guo and Yu, 1997;Rubboli et al, 1997) with two more family members added later (Lu et al, 1999;Lev et al, 1999). Lev et al (1999) designated the three genes Nir1, 2 and 3 because of their ability to interact with the protein tyrosine kinase PYK2 (PYK2 N-terminal domain-interacting receptors).…”

“…The sequence and structural similarities between the various mammalian PITPNM genes and the Drosophila rdgB gene, and the demonstration that these genes are all expressed in the mammalian retina (Aikawa et al, 1997;Chang et al, 1997;Guo and Yu, 1997;Rubboli et al, 1997;Lev et al, 1999;Lu et al, 1999) has led to the proposal that, as with the Drosophila gene, mutations in these genes may underlie certain forms of retinal disease in humans. In this paper we report the chromosomal localization and the genomic structure of these three genes, together with an evolutionary analysis of the origin of the different protein domains.…”

“…This discrepancy appears to be due to a nucleotide error in codon 1045 (the nucleotide sequence for the clone is not available). The reference sequence for PITPNM1 (NM_004910) is based on the sequence published by Rubboli et al (1997) for clone DRES9. However, comparison of all other published sequences as well as the sequence obtained by ourselves from clones isolated from an adult retinal cDNA library (GenBank accession number AY429102), indicate that there are sequence errors at codons 1116, which should encode a Glu and not Gly, and at 1133 which should encode an Ala not a Thr.…”

“…The fly gene was originally reported by Vihtelic et al (1993) to encode a 1,050-amino acid protein, although subsequent analysis by Rubboli et al (1997) reported the insertion of 2 C's at nucleotide positions 3587 and 3896 which extends the open reading frame to 1,250 amino acids. We have used the nucleotide sequence representing these 1,250 amino acids (NM_078594) in a comparison with Drosophila genomic sequence (AC011069).…”