common infection techniques used by these viruses and generally transcribe late viral genes. Subgenomic promoters range from 24 nucleotide (Sindbis virus) to over 100 nucleotides (Beet necrotic yellow vein virus) and are usually found upstream of the transcription start. Detection A wide variety of algorithms have been developed to facilitate detection of promoters in genomic sequence, and promoter prediction is a common element of many gene prediction methods. A promoter region is located before the -35 and -10 Consensus sequences. The closer the promoter region is to the consensus sequences the more often transcription of that gene will take place. There is not a set pattern for promoter regions as there are for consensus sequences. Evolutionary change Changes in promoter sequences are critical in evolution as indicated by the relatively stable number of genes in many lineages. For instance, most vertebrates have roughly the same number of protein-coding genes (about 20,000) which are often highly conserved in sequence, hence much of evolutionary change must come from changes in gene expression. De novo origin of promoters Given the short sequences of most promoter elements, promoters can rapidly evolve from random sequences. For instance, in E. coli, ~60% of random sequences can evolve expression levels comparable to the wild-type lac promoter with only one mutation, and that ~10% of random sequences can serve as active promoters even without evolution. Binding The initiation of the transcription is a multistep sequential process that involves several mechanisms: promoter location, initial reversible binding of RNA polymerase, conformational changes in RNA polymerase, conformational changes in DNA, binding of nucleoside triphosphate (NTP) to the functional RNA polymerase-promoter complex, and nonproductive and productive initiation of RNA synthesis. The promoter binding process is crucial in the understanding of the process of gene expression. Tuning synthetic genetic systems relies on precisely engineered synthetic promoters with known levels of transcription rates. Location Although RNA polymerase holoenzyme shows high affinity to non-specific sites of the DNA, this characteristic does not allow us to clarify the process of promoter location. This process of promoter location has been attributed to the structure of the holoenzyme to DNA and sigma 4 to DNA complexes. Diseases associated with aberrant function Most diseases are heterogeneous in cause, meaning that one "disease" is often many different diseases at the molecular level, though symptoms exhibited and response to treatment may be identical. How diseases of different molecular origin respond to