Human Lsg1 defines a family of essential GTPases that correlates with the evolution of compartmentalization.
BACKGROUND
Compartmentalization is a key feature of eukaryotic cells, but its evolution remains poorly understood. GTPases are the oldest enzymes that use nucleotides as substrates and they participate in a wide range of cellular processes. Therefore, they are ideal tools for comparative genomic studies aimed at understanding how aspects of biological complexity such as cellular compartmentalization evolved.


RESULTS
We describe the identification and characterization of a unique family of circularly permuted GTPases represented by the human orthologue of yeast Lsg1p. We placed the members of this family in the phylogenetic context of the YlqF Related GTPase (YRG) family, which are present in Eukarya, Bacteria and Archea and include the stem cell regulator Nucleostemin. To extend the computational analysis, we showed that hLsg1 is an essential GTPase predominantly located in the endoplasmic reticulum and, in some cells, in Cajal bodies in the nucleus. Comparison of localization and siRNA datasets suggests that all members of the family are essential GTPases that have increased in number as the compartmentalization of the eukaryotic cell and the ribosome biogenesis pathway have evolved.


CONCLUSIONS
We propose a scenario, consistent with our data, for the evolution of this family: cytoplasmic components were first acquired, followed by nuclear components, and finally the mitochondrial and chloroplast elements were derived from different bacterial species, in parallel with the formation of the nucleolus and the specialization of nuclear components.
Reynaud
Emmanuel G
EG
Cell Biology and Cell Biophysics Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Reynaud@embl.de
Andrade
Miguel A
MA
Bonneau
Fabien
F
Ly
Thi Bach Nga
TB
Knop
Michael
M
Scheffzek
Klaus
K
Pepperkok
Rainer
R
D002467:Cell Nucleus / Q000201:enzymology; D020541:Coiled Bodies / Q000201:enzymology; D017124:Conserved Sequence; D030562:Databases, Protein; D004721:Endoplasmic Reticulum / Q000201:enzymology; D019143:Evolution, Molecular; D020558:GTP Phosphohydrolases / Q000235:genetics*; D023281:Genomics; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D005810:Multigene Family; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity
D020558:GTP Phosphohydrolases; D006153:Guanosine Diphosphate; D011993:Recombinant Fusion Proteins; C510283:LSG1 protein, human