Gene conversion
Encyclopedia
Gene conversion is an event in DNA genetic recombination
, which occurs at high frequencies during meiotic
division but which also occurs in somatic cells. It is a process by which DNA sequence information is transferred from one DNA helix (which remains unchanged) to another DNA helix, whose sequence is altered.
It is one of the ways a gene may be mutated. Gene conversion may lead to non-Mendelian inheritance
and has often been recorded in fungal crosses.
, as can occur if there is sequence homology
, mismatch repair can alter the sequence of one of the chromosomes, so that it is identical to the other.
Gene conversion can result from the repair of damaged DNA as described by the Double Strand Break Repair Model. Here a break in both strands of DNA is repaired from an intact homologous region of DNA. Resection (degradation) of the DNA strands near the break site leads to stretches of single stranded DNA that can invade the homologous DNA strand. The intact DNA can then function as a template to copy the lost DNA. During this repair process a structure called a double Holliday structure
is formed. Depending on how this structure is resolved (taken apart) either cross-over or gene conversion products result.
) 'A', and one copy of allele 'a'). When a heterozygote creates gametes by meiosis
, the alleles normally split, and end up in a 1:1 ratio in the resulting cells. However, in gene conversion, a ratio other than the expected 1A:1a is observed, in which A and a are the two alleles. Such examples are 3A:1a, 1A:3a, 5A:3a or 3A:5a. In other words there can, for example, be three times as many A alleles as a alleles expressed in the daughter cells, as is the case in 3A:1a.
of a species. Every gene conversion event takes as its substrate two DNA sequences that are homologous but not identical, because of sequence mismatches, and yields two identical DNA sequences. Gene conversion forms the cohesive force that links DNA sequences within different organisms of a species
. Over time, gene conversion events yield a homogenous set of DNA sequences, both for allelic
forms of a gene and for multi gene families
. Interspersed repeats
act to block gene conversion events, thus catalyzing evolution of new genes and species.
.
Somatic gene conversion is one of the mechanisms that can result in familial retinoblastoma
, a congenital cancer of the retina
.
It is theorized that gene conversion may play a role in the development of Huntington's Disease
.
Genetic recombination
Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...
, which occurs at high frequencies during meiotic
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
division but which also occurs in somatic cells. It is a process by which DNA sequence information is transferred from one DNA helix (which remains unchanged) to another DNA helix, whose sequence is altered.
It is one of the ways a gene may be mutated. Gene conversion may lead to non-Mendelian inheritance
Non-mendelian inheritance
Non-Mendelian inheritance is a general term that refers to any pattern of inheritance in which traits do not segregate in accordance with Mendel’s laws. These laws describe the inheritance of traits linked to single genes on chromosomes in the nucleus. In Mendelian inheritance, each parent...
and has often been recorded in fungal crosses.
Mechanism
This conversion of one allele to the other is due to base mismatch repair during recombination: if one of the four strands during meiosis pairs up with one of the four strands of a different chromosomeChromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
, as can occur if there is sequence homology
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
, mismatch repair can alter the sequence of one of the chromosomes, so that it is identical to the other.
Gene conversion can result from the repair of damaged DNA as described by the Double Strand Break Repair Model. Here a break in both strands of DNA is repaired from an intact homologous region of DNA. Resection (degradation) of the DNA strands near the break site leads to stretches of single stranded DNA that can invade the homologous DNA strand. The intact DNA can then function as a template to copy the lost DNA. During this repair process a structure called a double Holliday structure
Holliday junction
A Holliday junction is a mobile junction between four strands of DNA. The structure is named after Robin Holliday, who proposed it in 1964 to account for a particular type of exchange of genetic information he observed in yeast known as homologous recombination...
is formed. Depending on how this structure is resolved (taken apart) either cross-over or gene conversion products result.
Effect
Normally, an organism that has inherited different copies of a gene from each of its parents is called heterozygous. This is generically represented as genotype: Aa (i.e. one copy of variant (alleleAllele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
) 'A', and one copy of allele 'a'). When a heterozygote creates gametes by meiosis
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
, the alleles normally split, and end up in a 1:1 ratio in the resulting cells. However, in gene conversion, a ratio other than the expected 1A:1a is observed, in which A and a are the two alleles. Such examples are 3A:1a, 1A:3a, 5A:3a or 3A:5a. In other words there can, for example, be three times as many A alleles as a alleles expressed in the daughter cells, as is the case in 3A:1a.
Importance of gene conversion in the cohesiveness of the gene pool
Gene conversion acts to homogenize the DNA sequences composing the gene poolGene pool
In population genetics, a gene pool is the complete set of unique alleles in a species or population.- Description :A large gene pool indicates extensive genetic diversity, which is associated with robust populations that can survive bouts of intense selection...
of a species. Every gene conversion event takes as its substrate two DNA sequences that are homologous but not identical, because of sequence mismatches, and yields two identical DNA sequences. Gene conversion forms the cohesive force that links DNA sequences within different organisms of a species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
. Over time, gene conversion events yield a homogenous set of DNA sequences, both for allelic
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
forms of a gene and for multi gene families
Gene family
A gene family is a set of several similar genes, formed by duplication of a single original gene, and generally with similar biochemical functions...
. Interspersed repeats
Interspersed repeat
Interspersed repetitive DNA is found in all eukaryotic genomes. Certain classes of these sequences propagate themselves by RNA mediated transposition, and they have been called retrotransposons. Interspersed repetitive DNA elements allow new genes to evolve. They do this by uncoupling similar DNA...
act to block gene conversion events, thus catalyzing evolution of new genes and species.
Medical relevance
Gene conversion resulting in mutation of the CYP21A2 gene is a common underlying genetic cause of congenital adrenal hyperplasiaCongenital adrenal hyperplasia
Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
.
Somatic gene conversion is one of the mechanisms that can result in familial retinoblastoma
Retinoblastoma
Retinoblastoma is a rapidly developing cancer that develops in the cells of retina, the light-detecting tissue of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers , with more than nine out of every ten sufferers surviving into...
, a congenital cancer of the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
.
It is theorized that gene conversion may play a role in the development of Huntington's Disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
.
External links
- images: http://www.web-books.com/MoBio/Free/Ch8D4.htm and http://www.web-books.com/MoBio/Free/Ch8D2.htm