Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins.
Level 5 - mechanism / opinion, no new human data
Bench and bioinformatic phylogenetic analysis; graded level 5 by design analogy
PubMed 10873683 · doi:10.1006/bbrc.2000.3000
What was done
The authors performed a molecular phylogenetic analysis of 60 conserved core domain sequences of Sir2-like proteins (sirtuins) across a wide range of organisms, including archaeans, bacteria, yeasts, plants, protozoans, and metazoans. They also examined the relationship of two human sirtuins, SIRT6 and SIRT7, to homologs in insects, nematodes, plants, and protozoans.
What was found
Eukaryotic Sir2-like proteins grouped into four primary branches, designated classes I through IV. Prokaryotic sirtuins appeared in classes II and III, while a fifth class was identified in gram-positive bacteria and Thermotoga maritima. Saccharomyces cerevisiae possessed five class I sirtuins. Caenorhabditis elegans and Drosophila melanogaster had sirtuin genes from classes I, II, and IV. The seven human sirtuins spanned all four eukaryotic classes: SIRT1, SIRT2, and SIRT3 in class I; SIRT4 in class II; SIRT5 in class III; and SIRT6 and SIRT7 in class IV.
Why it matters
This study established the standard phylogenetic classification scheme and nomenclature for the sirtuin family, defining the evolutionary relationships that group the seven human sirtuins into four distinct classes.
Limits
The analysis is restricted to in silico phylogenetic evaluation of 60 conserved core domain sequences available at the time, providing no in vitro enzymatic, cellular, or in vivo functional validation.
Cited by
- supports Humans have seven distinct sirtuin genes.