Archaea are characterized by their unique membrane lipids forming the hydrophobic core of the cell membrane. These membrane lipids are composed of isoprenoid sidechains stereospecifically linked to glycerol phosphate backbones(Figure 1). Atypical characteristics of these lipids distinguish them from bacterial and eukaryotic membrane lipids: isoprenoid, not fatty acids, sidechains; ether instead of ester bonds joining sidechains to the backbone; and stereochemistry of this backbone is sn-glycerol-1-phosphate, not sn-glycerol-3-phosphate. The biosynthesis of isoprenoid compounds depends on isoprenyl diphosphate synthases, which catalyze consecutive condensations of isopentenyl diphosphates with allylic primer substrates to form linear backbones for all isoprenoid compounds. Different isoprenyl diphosphate synthases determine the stereochemistry of the newly formed bonds and the final length of the isoprenoid products. The precursor of the archaeal isoprenoid sidechains, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), is synthesized through the mevalonate pathway similar to other isoprenoids in eukaryotes and some bacteria. However, most archaeal species lack the last three of the mevalonate enzymes: phosphomevalonate kinase (PMK), mevalonate diphosphate decarboxylase (MDC), and isopentenyl diphosphate isomerase (IDI1), whose function in the conversion of phosphomevalonate into IPP and DMAPP are replaced by the isopentenyl phosphate kinase (IPK) and an alternative isopentenyl diphosphate isomerase (IDI2)[2].

Mutational studies have demonstrated the extent of variety of isoprenyl diphosphate synthases corresponding to even the similar length of the isoprenoid products[4]. Therefore, the phylogenetic tree of the isoprenyl diphosphate synthases would provide much information for placing the unique archaeal isoprenyl production in an evolutionary context.

According to the Genetic Core of the Universal Ancestor, the majority of the universal genes are likely to play more fundamental roles in cellular processes[5]. Most of them were found to deal with RNA and DNA transcription, with the others mostly dealing with energy generation. The divergence of membrane lipids might suggest that the housing of the cell may have evolved separately and much later than would normally be assumed. Thanks to the significant accumulation of genome sequence data for a wide variety of archaea species, we can analyze the evolutionary relationship of archaeal isoprenyl diphosphate synthases without requiring labwork.

Phylogeny is one of the more interesting tools which allows for the recontextualization of a species into finding its place in the collection of evolutionary relationships shining new light on how similar the machinery is between all organisms. As was discussed in the introduction this was motivated by trying to place the isoprenyl production that uniquely makes up archaeal membranes in an evolutionary context to see where it may have come from. This result provides some surprising conclusions. As many of the eukaryote are much more closely tied to archaea then bacteria, an assumption that the 2 compared eukaryotes would have greater similarity between their geranylgeranyl diphosphate synthase which in archaea is referred to as bifunctional short chain isoprenyl diphosphate synthase. This turned out to be difficult to make a worse prediction. As can be seen in Figure 3 with the dramatically long tail to Homo sapiens and the amoeba Entamoeba histolytica. This indicates that there is a larger connection between bacterial metabolism and archaeal membranes then to their closer genetic relatives in Eukarya. This does make some sense as even though archaea and eukaryotes share much of their 16s gene, the eukaryotic membrane does not have the cyclic isoprenyl.