Resolving the homology—function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology

• Published in: Molecular and biochemical parasitology 2016-09, Vol.209 (1-2), p.88-103
• Main Authors: Klinger, Christen M., Ramirez-Macias, Inmaculada, Herman, Emily K., Turkewitz, Aaron P., Field, Mark C., Dacks, Joel B.
• Format: Article
• Language: English
• Subjects: Animals; Biological Evolution; Biological Transport; Carrier Proteins; Cell Membrane - metabolism; Endomembrane; Endosomal Sorting Complexes Required for Transport - metabolism; Eukaryota - genetics; Eukaryota - metabolism; Evolution, Molecular; Functional homology; Genome; Genomics; Genomics - methods; Membrane Proteins - metabolism; Membrane-trafficking; Parasite; Parasites - genetics; Parasites - metabolism; Protein Binding; Protein Transport; Protist
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/j.molbiopara.2016.07.003

•Genomics enables powerful advances in molecular and evolutionary parasitology.•Diverse model parasites allows for comparison of membrane-trafficking proteins.•Functional homology is largely observed in the membrane-trafficking system.•Endomembrane organization in poorly studied eukaryotes can be confidently inferred.•Unusual endomembrane organelles can be understood through relationships with canonical ones. 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.