Divergent functions through alternative splicing: the Drosophila CRMP gene in pyrimidine metabolism, brain, and behavior.
DHP and CRMP proteins comprise a family of structurally similar proteins that perform divergent functions, DHP in pyrimidine catabolism in most organisms and CRMP in neuronal dynamics in animals. In vertebrates, one DHP and five CRMP proteins are products of six genes; however, Drosophila melanogaster has a single CRMP gene that encodes one DHP and one CRMP protein through tissue-specific, alternative splicing of a pair of paralogous exons. The proteins derived from the fly gene are identical over 90% of their lengths, suggesting that unique, novel functions of these proteins derive from the segment corresponding to the paralogous exons. Functional homologies of the Drosophila and mammalian CRMP proteins are revealed by several types of evidence. Loss-of-function CRMP mutation modifies both Ras and Rac misexpression phenotypes during fly eye development in a manner that is consistent with the roles of CRMP in Ras and Rac signaling pathways in mammalian neurons. In both mice and flies, CRMP mutation impairs learning and memory. CRMP mutant flies are defective in circadian activity rhythm. Thus, DHP and CRMP proteins are derived by different processes in flies (tissue-specific, alternative splicing of paralogous exons of a single gene) and vertebrates (tissue-specific expression of different genes), indicating that diverse genetic mechanisms have mediated the evolution of this protein family in animals.
Molecular and Cellular Biology Group, Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA.
Deanna H
DH
Morris
Josh
J
Dubnau
Jae H
JH
Park
John M
JM
Rawls
D017398:Alternative Splicing; D000581:Amidohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D005091:Exons; D005123:Eye / Q000196:embryology; D005298:Fertility / Q000235:genetics; D005786:Gene Expression Regulation; D023061:Gene Order; D005838:Genotype; D008568:Memory; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055696:Olfactory Perception / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D020033:Protein Isoforms; D011743:Pyrimidines / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D014158:Transcription, Genetic
C576787:CRMP protein, Drosophila; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011743:Pyrimidines; D011993:Recombinant Fusion Proteins; D000581:Amidohydrolases; C020047:dihydropyrimidinase; C030986:pyrimidine