A phylogenetic survey of myotubularin genes of eukaryotes: distribution, protein structure, evolution, and gene expression.
BACKGROUND
Phosphorylated phosphatidylinositol (PtdIns) lipids, produced and modified by PtdIns kinases and phosphatases, are critical to the regulation of diverse cellular functions. The myotubularin PtdIns-phosphate phosphatases have been well characterized in yeast and especially animals, where multiple isoforms, both catalytically active and inactive, occur. Myotubularin mutations bring about disruption of cellular membrane trafficking, and in humans, disease. Previous studies have suggested that myotubularins are widely distributed amongst eukaryotes, but key evolutionary questions concerning the origin of different myotubularin isoforms remain unanswered, and little is known about the function of these proteins in most organisms.


RESULTS
We have identified 80 myotubularin homologues amidst the completely sequenced genomes of 30 organisms spanning four eukaryotic supergroups. We have mapped domain architecture, and inferred evolutionary histories. We have documented an expansion in the Amoebozoa of a family of inactive myotubularins with a novel domain architecture, which we dub "IMLRK" (inactive myotubularin/LRR/ROCO/kinase). There is an especially large myotubularin gene family in the pathogen Entamoeba histolytica, the majority of them IMLRK proteins. We have analyzed published patterns of gene expression in this organism which indicate that myotubularins may be important to critical life cycle stage transitions and host infection.


CONCLUSIONS
This study presents an overall framework of eukaryotic myotubularin gene evolution. Inactive myotubularin homologues with distinct domain architectures appear to have arisen on three separate occasions in different eukaryotic lineages. The large and distinctive set of myotubularin genes found in an important pathogen species suggest that in this organism myotubularins might present important new targets for basic research and perhaps novel therapeutic strategies.
Kerk
David
D
Department of Biological Sciences, University of Calgary, Alberta, Canada.
Moorhead
Greg B G
GB
D000595:Amino Acid Sequence; D056894:Amoebozoa / Q000235:genetics*; D000818:Animals; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D018129:Phosphatidylinositol Phosphates; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin