title: Resolving the homology-function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology.
abstract: With advances in DNA sequencing technology, it is increasingly common and tractable to informatically look for genes of interest in the genomic databases of parasitic organisms and infer cellular states. Assignment of a putative gene function based on homology to functionally characterized genes in other organisms, though powerful, relies on the implicit assumption of functional homology, i.e. that orthology indicates conserved function. Eukaryotes reveal a dazzling array of cellular features and structural organization, suggesting a concomitant diversity in their underlying molecular machinery. Significantly, examples of novel functions for pre-existing or new paralogues are not uncommon. Do these examples undermine the basic assumption of functional homology, especially in parasitic protists, which are often highly derived? Here we examine the extent to which functional homology exists between organisms spanning the eukaryotic lineage. By comparing membrane trafficking proteins between parasitic protists and traditional model organisms, where direct functional evidence is available, we find that function is indeed largely conserved between orthologues, albeit with significant adaptation arising from the unique biological features within each lineage.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Christen M
authors.initials: CM
authors.lastname: Klinger
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ramirez-Macias
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Herman
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Turkewitz
authors.affiliation: School of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dacks@ualberta.ca.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001692:Biological Transport; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D016678:Genome; D023281:Genomics / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism; D010271:Parasites / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D008565:Membrane Proteins
keywords: Endomembrane; Functional homology; Genomics; Membrane-trafficking; Parasite; Protist