TY - JOUR
T1 - Resolving the homology-function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology
AU - Klinger, Christen M.
AU - Ramirez-Macias, Inmaculada
AU - Herman, Emily K.
AU - Turkewitz, Aaron P.
AU - Field, Mark C.
AU - Dacks, Joel B.
N1 - Work in the Dacks lab is supported by a Discovery Grant RES0021028 from the Natural Sciences and Engineering Research Council. JBD is the Canada Research Chair in Evolutionary Cell Biology. CMK is funded by an Alberta Innovates Health Solution Fulltime Studentship and a Canada Vanier Graduate Scholarship. His research has been funded in part by the generosity of the Stollery Children's Hospital Foundation and supporters of the Lois Hole Hospital for Women through the Women and Children's Health Research Institute. EKH is funded by an Alberta Innovates Health Solution Fulltime Studentship and a Canada Vanier Graduate Scholarship. Work in the Turkewitz Lab is funded byNIH grant NIH-RO1 GM105783.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Membrane-trafficking
KW - Protist
KW - Parasite
KW - Genomics
KW - Function homology
KW - Endomembrane
U2 - 10.1016/j.molbiopara.2016.07.003
DO - 10.1016/j.molbiopara.2016.07.003
M3 - Article
C2 - 27444378
SN - 0166-6851
VL - 209
SP - 88
EP - 103
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
IS - 1-2
ER -