Wednesday, September 5, 2012

Origin of multicellularity – the bacterial connection

From Dayel et al.

Recently there has been some interest regarding work on the choanoflagellate Salpingoeca rosetta and it transition to multicellularity induced by the sulfonolipid produced by its prey, the bacteroidetes Algoriphagus (click to refer). This is interesting because it is consonant with a concept we have been articulating in print over the last 13 years: genetic material encoding particular protein domains which were horizontally transferred from bacteria were directly responsible for the origin of multicellularity in eukaryotes. We were first alerted to this possibility when we discovered the first caspases, AP-ATPases and TIR (Toll-interleukin) domains in bacteria ( click to refer). These molecules were just then emerging as key mediators of apoptosis in metazoans. This led to the idea that apoptosis, which is a key manifestation of multicellularity emerged directly on account of molecules acquired through lateral transfer from bacteria. We further developed this concept in a detailed sequence analysis of apoptosis mediators that became available as consequence of various genome projects and described this in a paper concomitant with the announcement of the human genome (click to refer). Subsequently, in another article we pointed out that many key aspect of multicellularity, both in terms of signaling and organization have had their ultimate origin in bacteria (click to refer). In terms of signaling, we were able to show that some major metazoan pathways such as the Notch pathway, which is involved in asymmetric cell-division, apoptotic pathways, and cell-cell signaling pathways, e.g. the nitric oxide signaling pathway have crystallized on account of components, whose origins lay in lateral transfers from bacteria. For example, in the Notch pathway the Swi2/Snf2 ATPase protein, Strawberry notch has emerged from bacterial DNA-modification systems related to restriction-modification systems. On the other hand, we showed that the nitric oxide/ carbon monoxide receptor domains emerged from comparable bacterial signaling domains (click to refer). On the organizational side, we were able to show that the origin of key cell-cell adhesion mediating domains (click to refer) also lay in bacteria – in particular we showed that the cadherin, Ig, FNIII and TIG domains emerged from various bacterial proteins with roles in cell-cell adhesion in bacteria, probably in the context of bacterial multicellularity and biofilm formation (click to refer). For a summary of our views one might refer to our paper on the origin of multicellularity (click to refer).

Our recent studies on 2-oxoglutarate and iron dependent (2OGFeDO) and Jumonji-related dioxygenases provide insights into the origins of a quintessential animal molecule collagen and the enzyme required for its biogenesis – the prolyl hydroxylase (click to refer). We uncovered several operons in bacteria that combine genes for one or more distinct 2OGFeDOs, namely amino acid beta-hydroxylase phytanoyl CoA and AlkB-like hydroxylases, with distinct versions of methyltransferase and sulfotransferase domains-containing proteins. These operons might also encode phosphoadenosine phosphosulfate synthetases, acetyltransferases either or both of two types of non-enzymatic proteins: (i) a member of the bacteriophage tail–collar family prototyped by the phage T4 short tail–fiber protein. (ii) Secreted glycine-rich peptides, some of which have a similar pattern of tripeptide repeats as seen in animal collagen. These operonic contexts suggest that the bacteria possessing them might produce collagen-like protein, which are modified by hydroxylation just like their animal counterparts. Indeed, this suggests that a collagen-precursor and its modifying enzymes were acquired from a bacterial source through the lateral transfer of such an operon played a role in the origin of animal by furnish a major component of animal extracellular matrices. Interestingly, the presence of sulfotransferase and phosphoadenosine phosphosulfate synthetases points to sulfate modification, which are also an essential feature of the animal extracellular matrices. On a more general note we observed that related sulfotransferases are fused to Jumonji-related extracellular dioxygenases of the FIH1 family in the choanoflagellate Monosiga (in most organisms they are intracellular and even nuclear proteins). This is particularly interesting in the context of the multiply hydroxylated sulfonolipid reported as being the multicellularity inducing agent secreted by Algoriphagus. Indeed the phytanoyl CoA hydroxylase-like, FIH1-like and sulfotransferase enzymes found in these operons can potentially participate in the synthesis of such metabolites. Therefore, we already have potential candidates for the biosynthesis of the multicellularity inducing agent and also evidence that genes for the synthesis of such molecules have been laterally transferred from bacteria to choanoflagellates.

In more recent times we have been particularly interested in protein toxins and other effectors deployed in intra- and inter- genomic and organismal conflict across life. These studies have also yield a several key clues regarding the bacterial contributions to the emergence of multicellularity among eukaryotes, including metazoans. Several such contributions have been described in our recent monograph of polymorphic toxin systems (click to refer) and will be outlined in a future post.