These systems instead rely on epigenetic modifications to control gene activation and silencing, the hallmarks of which include histone modifications, the use of modified nucleotides, changes in chromatin structure and nuclear organization. Gene silencing and activation within the family is therefore coordinated and strictly mutually exclusive.Īlthough many of the genetic systems underlying antigenic variation - for example, slipped-strand mispairing or gene conversion - involve alterations to the genome, in several organisms changes in gene expression do not involve any alterations in the primary DNA sequence. In these organisms, each individual gene has all of the elements necessary for expression, and each undergoes silencing and activation as described above however, there is an additional layer of regulation to ensure that only a single gene is active at any particular time. In more sophisticated systems, the pathogen has evolved large, multicopy gene families, with each copy encoding a different form of the surface antigen. The sequence of the expressed gene changes by gene conversion (or duplicative transposition) of large or small DNA sequences from the silent pseudogenes into the expression site. In other organisms, a single expression site is present for a key protein, with multiple silent gene copies or cassettes present elsewhere in the genome. In its simplest form, this entails changes in the expression of genes that are regulated individually, an on–off process referred to as phase variation. Some systems of antigenic variation involve the activation and silencing of genes that encode molecules exposed to the immune system of the infected host.

Molecules displayed on the cell surface of pathogens often mediate adhesion within specific niches and are frequently virulence determinants. The process of antigenic variation is focused at the host–pathogen interface, and in particular at the cell surface of the infectious organisms. This process of coevolution has resulted in the development of complex genetic systems that underlie antigenic variation by numerous pathogenic microorganisms. Bacterial, protozoan and fungal pathogens have responded by evolving equally elaborate systems to avoid destruction by their hosts. Mammals have evolved an elaborate, multifaceted immune system to respond to the ever-present threat of infection by pathogenic microorganisms.

Variation of phase ten