Characterization of the deleted in autism 1 protein family: implications for studying cognitive disorders

Autor: Naomi E. Bishop, Azhari Aziz, Sean P. Harrop
Rok vydání: 2010
Předmět:
Protein family
Neurological Disorders/Developmental and Pediatric Neurology
Amino Acid Motifs
Evolutionary Biology/Bioinformatics
lcsh:Medicine
Golgi Apparatus
Computational Biology/Computational Neuroscience
Computational Biology/Comparative Sequence Analysis
Biology
Protein Sorting Signals
Neurological Disorders
Conserved sequence
Evolution
Molecular
Computational Biology/Molecular Genetics
Computational Biology/Protein Homology Detection
Branchiostoma floridae
Intellectual Disability
Gene duplication
Animals
Humans
Autistic Disorder
lcsh:Science
Zebrafish
Conserved Sequence
Genetics
Cephalochordate
Evolutionary Biology
Multidisciplinary
Evolutionary Biology/Evolutionary and Comparative Genetics
lcsh:R
Membrane Proteins
Computational Biology
biology.organism_classification
Biological Evolution
CXorf36
Vertebrates
Computational Biology/Sequence Motif Analysis
Evolutionary Biology/Morphogenesis and Cell Biology
lcsh:Q
Human genome
Drosophila
Cognition Disorders
Research Article
Zdroj: PLoS ONE
PLoS ONE, Vol 6, Iss 1, p e14547 (2011)
ISSN: 1932-6203
Popis: Autism spectrum disorders (ASDs) are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1) and cXorf36 or Deleted in Autism-1 Related (DIA1R) are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L), lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental retardation.
Databáze: OpenAIRE
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