Inositol and its derivatives: their evolution and functions.

Ins and Ins phospholipids are present in and are made by most Archaea and all eukaryotes. Relatively few bacteria possess Ins phospholipids: and only one major grouping, the Actinobacteria, is known to have evolved multiple functions for Ins derivatives. The Ins phospholipids of all organisms, whether they have diradylglycerol or ceramide backbones, seem to use the same Ins1P headgroup stereochemistry, so they are probably made by evolutionarily conserved pathways. It seems likely that an early member of the Archaea made the first phospholipid with an Ins1P headgroup -maybe three billionyears ago – and that amuchlater archaeal descendentwas the ancestral contributor that brought these molecules into the common ancestor of all eukaryotes – maybe two billionyears ago (Michell, 2007, 2008). It will only be possible to infer the likely details of these processes when we have learned much more about the Ins lipid biochemistry of modern archaeons. All eukaryotes make substantial amounts of PtdIns, both as a ‘bulk’ membrane phospholipid and as the precursor of seven phosphorylated derivatives of PtdIns (the polyphosphoinositides; PPIn) and of the ‘GPI anchors’ of cell surface ectoproteins. PtdIns(4,5)P2 – with its many functions – and its precursor PtdIns4P are found in all in eukaryotes. So are PtdIns3P and PtdIns(3,5)P2, which have ubiquitous roles in the regulation of membrane trafficking events. However, synthesis of and signalling by PtdIns(3,4,5) P 3 appears to be confined to a later-evolved group of eukaryotes.