the aptamer, but can be further classified into Class I (Cbl-I) and Class II (Cbl-II) based on cobalamin analogue selectivity and peripheral structural elements. Cbl-I and Cbl-II riboswitches share a conserved receptor domain composed of a four-way junction and regulatory domain. Cbl-I riboswitches are selective for AdoCbl, with a variable peripheral stem loop structure facilitating ligand specificity. Over 90% of cobalamin riboswitches identified before 2003 are Cbl-I riboswitches. Class IIa (Cbl-IIa) Cbl-II can be further divided into two classes (Cbl-IIa and Cbl-IIb). Cbl-IIa riboswitches are specific to cobalamin analogues with smaller β-axial ligands including MeCbl and HyCbl. This selectivity is determined by peripheral element variations. Class IIb (Cbl-IIb) Cbl-IIb riboswitches are also selective for AdoCbl, but they differ significantly in structure from Cbl-I riboswitches. The structural basis for AdoCbl selectivity has not yet been determined. Cbl-IIb riboswitches also differ in terms of the nature of the genes they regulate, with Cbl-IIb riboswitches primarily associated with genes involved in ethanolamine utilization. Ethanolamine is abundant in the human intestinal tract as it is the product of the breakdown of the phosphatidylethanolamine from cell membranes and is also present in processed food. Most bacteria that inhabit the intestinal tract can utilize ethanolamine as a carbon and nitrogen source by upregulating the expression of the ethanolamine utilization genes; this may have a survival advantage. The expression of the ethanolamine utilization genes (eutG) is influenced by two different mechanisms. The first is a two component regulatory system that senses the presence of ethanolamine and the second mechanism is an AdoCbl riboswitch that senses the presence of AdoCbl, a cofactor needed for the breakdown of ethanolamine. A study showed that both these regulatory elements need to be activated for the bacteria to grow efficiently on medium containing ethanolamine. Bioinformatic studies were initially unsuccessful in identifying AdoCbl riboswitches within the bacteria genomes, but subsequent studies of the intergenic regions of the eutG locus using Ribex identified an RNA element between the eutT and eutG genes. In addition, some cobalamin riboswitches exhibit promiscuous ligand binding, such as the B. subtilis yvrC riboswitch, which can adopt different structural conformations in order to bind cobalamin analogues with smaller β-axial ligands such as MeCbl and HyCbl in addition to AdoCbl, which has a much bulker β-axial moiety. This riboswitch is also capable of binding CyCbl. Discovery Before proof of riboswitch function, a conserved sequence motif called the B12 box was identified