Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies

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Genome sequencing projects have identified large numbers of genes that encode proteins of unknown function. Many of these genes show strong evolutionary conservation, predicting important and well-conserved functions. A fraction of these show strong conservation of core domains but dynamic changes in other domains, predicting both conserved and lineage-dependent functions. Here we identify neurological functions associated with one such gene identified by a forward genetic screen in mice. We use recently developed genome editing tools both to confirm the mouse studies and to test comparative functions in a model insect, the fruit fly Drosophila melanogaster. Each of these species has a single homolog of this gene family, but differ by inclusion of a ras-association (RA) domain present in most invertebrate species but missing in mammals. Null mutations in both mice and flies produce neurological phenotypes, but while the mouse phenotypes are comparatively mild (vestibular deficits, mild tremor, hyperactivity, mild circadian phenotypes and abnormal fear learning–but normal viability and breeding), null flies rarely survive to adulthood and surviving flies have severe locomotor deficits. Interestingly, heterozygous flies have significant sleep-related phenotypes. Together, our results provide a detailed first look at comparative function for a gene lineage with an unusual evolutionary history.

Vyšlo v časopise: Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005344
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005344

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