Gene Duplication in Early Vertebrates Results in Tissue-Specific Subfunctionalized Adaptor Proteins: CASP and GRASP

• Published in: Journal of molecular evolution 2008-08, Vol.67 (2), p.168-178
• Main Authors: MacNeil, Adam J, McEachern, Lori A, Pohajdak, Bill
• Format: Article
• Language: English
• Subjects: Adaptor protein; Amino Acid Sequence; Amino acids; Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Branchiostoma lanceolatum; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Biology; Chordata; Cytohesin; Evolutionary Biology; Gene Duplication; Genes; Genome - genetics; Humans; Immune system; Life Sciences; Marine; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microbiology; Molecular Sequence Data; Nuclear receptor 4A; Organ Specificity; Paralogue; PDZ domain protein; PDZ-binding motif; Phylogeny; Plant Genetics and Genomics; Plant Sciences; Protein family; Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Studies; Subfunctionalization; Tissues; Vertebrates; Vertebrates - genetics; Vertebrates - metabolism
• ISSN: 0022-2844; 1432-1432
• DOI: 10.1007/s00239-008-9136-y

CASP and GRASP are small cytoplasmic adaptor proteins that share highly similar protein structures as well as an association with the cytohesin/ARNO family of guanine nucleotide exchange factors within the immune and nervous systems respectively. Each contains an N-terminal PDZ domain, a central coiled-coil motif, and a carboxy-terminal PDZ-binding motif (PDZbm). We set out to further characterize the relationship between CASP and GRASP by comparing both their gene structures and their functional motifs across several vertebrate organisms. CASP and GRASP not only share significant protein structure but also share remarkably similar gene structure, with six of eight exons of equal length and relative position. We report on the addition of a unique amino acid within the coiled-coil motif of CASP proteins in several species. We also examine the Class I PDZbm, which is highly conserved across all classes of vertebrates but shows a functionally relevant mutation in the CASP proteins of several species of fish. Further, we determine the evolutionary relationship of these proteins both by use of phylogenetics and by comparative analysis of the conservation of genes near each locus in various chordates including amphioxus. We conclude that CASP and GRASP are the products of a relatively recent gene duplication event in early vertebrate organisms and that the evolution of the adaptive immune system and complex brain most likely contributed to the apparent subfunctionalization of these proteins into tissue-specific roles.