elucidate the evolution of virulence, as well as provide necessary information for treatment. Likewise understanding the specific changes in structural gene sequences underlying a gain or loss of virulence aids in understanding the mechanism by which diseases affect their hosts. For example, Yersinia pestis (the bubonic plague) was found to carry several virulence and inflammation-related structural genes on plasmids. Likewise, the structural gene responsible for tetanus was determined to be carried on a plasmid as well. Diphtheria is caused by a bacterium, but only after that bacterium has been infected by a bacteriophage carrying the structural genes for the toxin. In Herpes simplex virus, the structural gene sequence responsible for virulence was found in two locations in the genome despite only one location actually producing the viral gene product. This was hypothesized to serve as a potential mechanism for strains to regain virulence if lost through mutation. Understanding the specific changes in structural genes underlying a gain or loss of virulence is a necessary step in the formation of specific treatments, as well the study of possible medicinal uses of toxins. Phylogenetics As far back as 1974, DNA sequence similarity was recognized as a valuable tool for determining relationships among taxa. Structural genes in general are more highly conserved due to functional constraint, and so can prove useful in examinations of more disparate taxa. Original analyses enriched samples for structural genes via hybridization to mRNA. More recent phylogenetic approaches focused on structural genes of known function, conserved to varying degrees. rRNA sequences frequent targets, as they are conserved in all species. Microbiology has specifically targeted the 16S gene to determine species level differences. In higher-order taxa, COI is now considered the “barcode of life,” and is applied for most biological identification. Debate Despite the widespread classification of genes as either structural or regulatory, these categories are not an absolute division. Recent genetic discoveries call into question the distinction between regulatory and structural genes. The distinction between regulatory and structural genes can be attributed to the original 1959 work on Lac operon protein expression. In this instance, a single regulatory protein was detected that affected the transcription of the other proteins now known to compose the Lac operon. From this point forward, the two types of coding sequences were separated. However, increasing discoveries of gene regulation suggest greater complexity. Structural gene expression is regulated by numerous factors including epigenetics (e.g. methylation),