Aplysia image courtesy of Dr. Leonid Moroz, University of Florida, Gainesville, FL.Do sea slugs get dementia? Moroz et al. report Aplysia orthologs of genes associated with human neurological disorders, including Alzheimer and Parkinson diseases, in a recent article in Cell.
Aplysia have roughly 99 billion fewer neurons than mammals, and each Aplysia neuron can be 10-100 times larger than the average mammalian neuron. Researchers have identified the Aplysia neurons involved in learning and reflex behaviors, but a lack of genomic information has precluded the identification of molecular mechanisms.
The authors sequenced cDNA libraries of the Apylsia nervous system and identified over 175,000 expressed sequence tags. In all, they found 19,814 unique transcripts, representing 50-70% of the predicted number of transcripts in the Aplysia nervous system, according to the authors. Their data are freely available in an online database.
Sequence analysis showed that Aplysia are closely related to mammals. Fewer amino acids differed between predicted Aplysia and human proteins than between Drosophila or C. elegans and human proteins. The authors detected orthologs for P2X receptor genes encoding ATP receptors, the cysteine protease inhibitor cystatin B, ependymin-like neurotrophic factor and selenoproteins in Aplysia, but not Drosophila.
Might Aplysia be used to model human neurological diseases? The authors found 104 orthologs to 146 human genes associated with neurological dysfunction. They identified homologs for human disease-related genes that were not expressed in Drosophila, including fukutin, CLN8 and GM2 activator protein, which are associated with muscular dystrophy, epilepsy and Tay-Sachs disease, respectively, or in C. elegans, including huntingtin and fragile X mental retardation protein. The authors also identified genes necessary for RNA interference, suggesting a mechanism for gene silencing in Aplysia.
Aplysia reflexively withdraw their gills following siphon stimulation. This gill-withdrawal reflex is mediated by sensory neurons in the siphon and L7 motor neurons in the gill. Using microarrays, the authors found 362 genes that were enriched in L7 but not sensory neurons, and 491 genes that were enriched in sensory but not L7 neurons. From the list of genes enriched in L7 neurons, the authors identified several candidate neurotransmitters that might signal gill withdrawal, including the opioid-like peptide, mytilus inhibitory peptide-related precursor, and PTSP, which is related to a hormone involved in silkworm development.
The authors found almost 10,000 transcripts in serotonergic metacerebral cell cDNA libraries, the most abundant of which included serotonin transporters and pheromone receptors, according to Gene Ontology analysis. Analysis of cDNA libraries from metacerebral cell neurites showed several genes, including actin and ubiquitin, preferentially expressed in metacerebral cell neurites relative to cell bodies.
The Aplysia transcriptome will help identify genes that differentiate distinct types of neuron and genes important in the function of neuronal circuits. Identification of orthologs to Aplysia candidate genes should extend these findings to vertebrates and other invertebrates.