Signature-tagged mutagenesis (STM) is a

genetic Genetic may refer to: *Genetics, in biology, the science of genes, heredity, and the variation of organisms **Genetic, used as an adjective, refers to genes ***Genetic disorder, any disorder caused by a genetic mutation, whether inherited or de nov ...

technique used to study

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

function. Recent advances in

genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...

have allowed us to catalogue a large variety of organisms' genomes, but the function of the genes they contain is still largely unknown. Using STM, the function of the product of a particular gene can be inferred by disabling it and observing the effect on the organism. The original and most common use of STM is to discover which genes in a

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...

are involved in

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...

in its

host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places *Host, Pennsylvania, a village in Berks County People * Jim Host (born 1937), American businessman * Michel Host ...

, to aid the

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped *Photographi ...

of new medical therapies/drugs.

Basic premise

The gene in question is inactivated by insertional

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

; a

transposon A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transp ...

is used which inserts itself into the gene sequence. When that gene is transcribed and

translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

into a protein, the insertion of the transposon affects the protein structure and (in theory) prevents it from functioning. In STM, mutants are created by random transposon insertion and each transposon contains a different 'tag' sequence that uniquely identifies it. If an insertional mutant bacterium exhibits a

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...

of interest, such as susceptibility to an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...

it was previously resistant to, its genome can be sequenced and searched (using a computer) for any of the tags used in the experiment. When a tag is located, the gene that it disrupts is also thus located (it will reside somewhere between a start and stop

codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

which mark the boundaries of the gene). STM can be used to discover which genes are critical to a pathogen's virulence by injecting a 'pool' of different random mutants into an

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

(e.g. a mouse infection model) and observing which of the mutants survive and proliferate in the host. Those mutant pathogens that ''don't'' survive in the host must have an inactivated gene, required for virulence. Hence, this is an example of a negative selection method.

References

* Genetics Mutagenesis {{Genetics-stub