T Cell Receptor, Evolution of

Lee Rowen , in Encyclopedia of Immunology (2nd Edition), 1998

Cistron conversion

Gene conversion is a unidirectional commutation of sequence information between like sequences, wherein 1 stretch of sequence is used every bit a template to 'repair' or 'correct' another stretch of sequence. Because the TCR loci are multigene families, with many regions of similar sequence due to duplications, gene conversion is likely to be common. Depending on the length of the converted region, which can vary from a few bases to many kilobases, gene conversion can be either a diversifying or a homogenizing force in development. The homogenizing consequence of factor conversion has occurred independently in the constant cistron segments of the β locus in several species (e.g. human, mouse and salamander). Although the D–J–C duplication in the β locus probably occurred early in tetrapod evolution (craven lacks this duplication), the abiding gene segments in each species investigated behave more than intraspecies similarity than interspecies similarity. This suggests that there are species-specific constraints, such as a need to bind to accessory proteins, that exert selective pressure on the Cβ genes, leading to their concerted evolution.

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Man Genomic Variants and Inherited Disease

Stylianos E. Antonarakis , David N. Cooper , in Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics (Seventh Edition), 2019

6.iii.13 Cistron Conversion

Gene conversion is the modification of ane of two alleles by the other. Information technology involves the nonreciprocal correction of an "acceptor" cistron or Dna sequence by a "donor" sequence, which itself remains physically unchanged. In nearly known instances of gene conversion as a cause of homo genetic disease, the functional gene has been wholly or partially converted to the sequence of a highly homologous and closely linked pseudogene, which therefore acts as the donor sequence [292]. Probable examples include the genes for steroid 21-hydroxylase (CYP21 [293]), polycystic kidney disease (PKD1 [294]), neutrophil cytosolic factor p47-phox (NCF1 [295]), immunoglobulin λ-like polypeptide 1 (IGLL1 [296]), glucocerebrosidase (GBA [297]), von Willebrand gene (VWF [298]), and phosphomannomutase (PMM2 [299]). These gene/pseudogene pairs are all closely linked with the exception of the VWF cistron (12p13) and its pseudogene (22q11–q13) and the PMM2 gene (16p13) and its pseudogene (18p). Together, these two exceptions would seem to plant a precedent for the occasional occurrence of gene conversion betwixt unlinked loci in the human genome.

An in silico analysis of the Deoxyribonucleic acid sequence tracts involved in 27 well-characterized nonoverlapping gene conversion events in nineteen different genes reported in the context of inherited disease was recently performed [300]. It was noted that gene conversion events tended to occur within (C+G)- and CpG-rich regions and that sequences with the potential to class non-B DNA structures (and which might be involved in the generation of double-strand breaks that could, in turn, serve to promote cistron conversion) occurred disproportionately within maximal converted tracts and/or curt flanking regions. Maximal converted tracts were besides establish to be enriched in a truncated version of the chi-element (a TGGTGG motif), immunoglobulin heavy chain class switch repeats, translin target sites, and several novel motifs including (or overlapping) the classic meiotic recombination hotspot, CCTCCCCT [300]. Finally, it was plant that gene conversions tended to occur in genomic regions that had the potential to fold into stable hairpin conformations. Taken together, these findings support the concept that recombination-inducing motifs, in association with alternative (non-B DNA) conformations, tin can promote recombination in the man genome.

The large number of duplicated gene sequences in the human genome implies that a considerable number of disease-associated variants could originate via interlocus cistron conversion. A genome-wide computational arroyo to identify illness-associated variants derived from interlocus gene conversion events recently revealed hundreds of known pathological variants that could have been caused past interlocus gene conversion [301]. In addition, several dozen high-confidence cases of inherited illness variants resulting from interlocus cistron conversion were identified in ∼1% of all genes analyzed. Near half of the donor sequences associated with such variants were functional paralogous genes, suggesting that epistatic interactions or differential expression patterns would determine the impact upon fitness of a single amino acid commutation betwixt duplicated genes. In addition, Casola et al. [301] identified thousands of hitherto undescribed deleterious variants that could potentially arise via interlocus gene conversion. Information technology would therefore appear that the impact of interlocus factor conversion upon the spectrum of human inherited affliction may be considerably greater than has hitherto been appreciated.

Although variants that are detrimental to the fitness of individuals are expected to exist rapidly purged from the population past natural selection, some pathological variants are yet retained at high frequencies in human populations. Several hypotheses have been proposed to account for this credible paradox (loftier new mutation rate, genetic drift, overdominance, or recent changes in selective pressure). However, in that location is an additional process that appears to contribute to the spreading of deleterious variants: GC-biased gene conversion (gBGC), a process associated with recombination that tends to favor the transmission of GC-alleles over AT-alleles. Necsulea et al. [302] take shown that the spectrum of amino acrid–altering polymorphisms in human populations exhibits the footprints of gBGC. This blueprint is not explicable in terms of selection and is axiomatic with all nonsynonymous variants, including those predicted to exist detrimental to poly peptide structure and function as well as those that have been implicated in the causation of human genetic disease. These results signal that gBGC meiotic drive contributes to the spreading of deleterious variants in man populations.

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Genome Instability in Bacteria

A.B. Williams , in Genome Stability, 2016

4.2 Gene Conversion

Gene conversion occurs when two related but divergent sequences be in the aforementioned cell and tin be substrates for recombination [78]. The effect of gene conversion is a unidirectional transfer of genetic sequence information from a donor sequence into a highly like recipient sequence. One of the nearly studied outcomes of factor conversion in bacteria is the type IV pilus antigenic variation in Neisseria gonorrhoeae [79]. Antigenic variation leads to phenotypic heterogeneity within a genetically clonal bacterial population, as different cells tin limited one of a several possible antigenic formsof a poly peptide. In N. gonorrheae, the antigenic hair variants are due to the differences in the construction of the pilin protein. Each pilin variant shares a conserved North-terminal region but they differ in the C terminus. The conserved role of pilin is encoded past the pilE locus and the variable segment of the protein is encoded by up to vi dissimilar nontranscribed or weakly transcribed pilS loci [fourscore,81]. The expression of a full length, functional pilin protein requires a gene conversion upshot in which one of the silent pilS loci is transferred to the pilE locus via a recombination reaction mediated by RecA and RecOR. While the pilE locus is genetically unstable, the gene conversion event has no event on the pilS loci. The biological forces driving pilin antigenic variation in N. gonorrhoeae are non fully understood; withal, iron levels may influence the frequency of antigenic variation and it may be of import during transfer into new hosts [82].

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Mating Systems in Plants, Genome Development and

A. Muyle , 1000. Marais , in Encyclopedia of Evolutionary Biology, 2016

Convenance Systems and the Development of Genome Base Limerick

Biased factor conversion (BGC) is a molecular process associated with recombination that drives genomic base composition toward a loftier GC content ( Figure 3) (Lesecque et al., 2013; Marais, 2003), which was shown to affect plant genomes (Glémin et al., 2014; Serres-Giardi et al., 2012; Muyle et al., 2011). Because BGC will operate when recombination occurs in heterozygous loci, it will increment GC content in outcrossing and non in purely selfing species (Marais et al., 2004). Because of the absenteeism of recombination in asexuals, BGC should not touch on GC content in these species. Also, every bit the effect of BGC is dependent on Due north e (Lartillot, 2013), it should be reduced in selfers.

Effigy three. Possible mechanisms for the biased factor conversion (BGC). Dissimilar pathways for double-strand pause (DSB) repair during meiotic recombination are shown in (a). Blueish and crimson chromosomes indicate chromosomes from different parental origin. Recombination starts with the DSBs on one chromosome. Cleaved DNA is resected forming unmarried-stranded DNA, which volition be used to select a template for repairing the breaks. The mismatch repair (MMR) triggers the selection of template: if the degree of similarity between the single-stranded DNA and the potential template is sufficient, the template is invaded and a D-loop is formed. Otherwise, repair takes place by using the sister chromatin, no recombination happens. Recombination can take place by several pathways: the repair of the breaks by the MMR can atomic number 82 to the germination of a double-Holliday junction (dHj) intermediate. Resolution of this intermediate may result in crossovers (COs) of grade 1, i.e., showing CO interference (a mechanism by which 1 CO / arm / meiosis is ensured). Another pathway (Mus81) produces non-interfering COs. And the synthesis-dependent strand annealing (SDSA) pathway gives non-crosser (gene conversion) events only. Heteroduplexes (Dna with strands from different origins) tin can be found at various stages of the recombination pathway; they may include mismatches that are detected and repaired by unlike pathways (MMR and base of operations-excision repair (BER)). BGC may event from different possible biases. (b) Initiation bias. If A/T alleles are recombinationally hotter than Grand/C alleles, K/C alleles will get re-create-pasted onto the A/T alleles (recombination hot spots get converted by recombination cold spot, see the 'hot spot paradox,' Lesecque et al., 2014), and this will increase GC content. (c) Choice of template bias. If the chance of the single-stranded DNA to invade the homologous chromosome is higher when it is GC-rich, this will also create BGC. (d) Repair bias. If repair of mismatches in heteroduplexes is biased in favor of G/C alleles, this may too generate BGC. A recent study in yeast suggests that BGC is found by and large associated with long gene conversion tracts and CO and may be due to MMR (Lesecque et al., 2013). While bear witness for BGC have been found in many organisms (Pessia et al., 2012), in most cases the exact mechanism remains unknown and could be 1 of the three mechanisms outlined hither. Adjusted from Lesecque, Y., Mouchiroud, D., Duret, Fifty., 2013. GC-biased gene conversion in yeast is specifically associated with crossovers: Molecular mechanisms and evolutionary significance. Molecular Biology and Evolution xxx, 1409–1419. doi:10.1093/molbev/mst056.

Observations fitted expectations for non-coding Dna (higher GC content in outcrossing Poaceae, Glémin et al., 2006), unless a too small intron dataset was used (Brassicaceae, Qiu et al., 2011). But studies using coding sequences gave conflicting results in Triticeae (Escobar et al., 2010; Haudry et al., 2008), or supported BGC only could non distinguish information technology from mutational biases in other groups (Hazzouri et al., 2013; Wright et al., 2007). More studies comparing selfing and outcrossing species are required, with appropriate methods that permit to distinguish BGC from mutational biases (equilibrium GC content, GC*, that a genome reaches if mutation and commutation rates remain constant, or derived allele frequency spectra) and big not-coding datasets in order to distinguish BGC from selection on codon usage. Similar studies also accept to be carried out in asexual and sexual species.

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Reciprocal Recombination☆

F.W. Stahl , in Reference Module in Life Sciences, 2017

Relationship to Gene Conversion

Meiotic gene conversion, a nonreciprocal route to recombination, can be understood within the double-strand-break repair scheme described before. Dna lost by the preinvasion digestion of the 5′-ended strands of the cutting chromosome is replaced by copying the homolog. Any genetic marker located in that segment of the chromosome will no longer be represented normally in the tetrad, because five single strands volition correspond to the genotype of ane parent and 3 strands to the other parent (five:three tetrad, half conversion). The inequality tin be enlarged to a 6:2 ratio (full conversion) by the loss of nucleotide sequences from the invading, iii′-ended strand that is in hybrid Dna. Such loss is frequently the result of the activity of a mismatch-repair system that recognizes the local noncomplementarity resulting from the mark divergence between the two homologs and excises a segment of the three′-ended strand, which is and so replaced using the homolog as template. A half dozen:2 segregation could also consequence if the three′-ended, as well as the v′-concluded, strand at the initiating double-strand pause is sometimes degraded.

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Mutagenicity and Carcinogenicity of African Medicinal Plants

Jean-de-Dieu Tamokou , Victor Kuete , in Toxicological Survey of African Medicinal Plants, 2014

10.4.1.2.4 The Saccharomyces cerevisiae Mitotic Recombination Assay

Mitotic recombination (factor conversion or crossing-over) in Saccharomyces cerevisiae tin be detected between genes (or more generally betwixt a gene and its centromere) and within genes following treatment with a mutagen. These recombinations are essentially DNA exchanges between segments of homologous chromatids and this assay gives an indication of non-specific DNA damage. The former event is called mitotic crossing-over and generates reciprocal products, whereas the latter consequence is near oft nonreciprocal and is called factor conversion. The most commonly used strains for the detection of mitotic gene conversion are Dfour (heteroallelic at ade2 and trp5); Dseven (heteroallelic at trp5); BZ34 (heteroallelic at argfour), and JDl (heteroallelic at hisfour and trp5). Mitotic crossing-over producing cerise and pink homozygous sectors can be assayed in D5 or in D7 (which also measures mitotic gene conversion and reverse mutation at ilvi-92) both strains beingness heteroallelic for complementing alleles of ade2.

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Adrenal cortex and its disorders

Walter L. Miller Dr. , Christa E. Flück Doctor , in Pediatric Endocrinology (Fourth Edition), 2014

Glucocorticoid-suppressible hyperaldosteronism

Although CYP11B gene conversions are rare, an unusual cistron duplication causes glucocorticoid-suppressible hyperaldosteronism. A homologous recombination effect creates a third CYP11B cistron that fuses the v′ flanking DNA of the CYP11B1 cistron for P450c11β onto the CYP11B2 gene for P450c11AS, thus placing the regulation of P450c11AS under the control of ACTH rather than the renin-angiotensin system, and then that these patients make P450c11AS in response to physiology that should stimulate P450c11β. 131 The excess P450c11AS causes hyperaldosteronism and hypertension; this is then suppressible by glucocorticoid suppression of ACTH, which normally suppresses P450c11β, hence the proper noun "glucocorticoid-remediable hypertension"; this disorder appears to business relationship for almost 2% of hypertension. 132

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Built Adrenal Hyperplasia

Saroj Nimkarn , Maria I. New , in Genetic Diagnosis of Endocrine Disorders, 2010

Complexity of the Active Genes and their Nearby Pseudogenes

A big calibration gene conversion tin transfer sequences containing more than than one mutation from the pseudogene to the agile gene. In this instance, targeted mutation analysis that aims to screen for common mutations may detect multiple mutations. The method volition non distinguish whether the mutations lie on the same allele representing only ane mutant allele or the mutations lie on both alleles. To avoid such potential errors, studying both parents too every bit the proband is recommended to confirm the mutations and to determine if they are in the cis configuration or the trans configuration.

Another potential cause of misdiagnosis is duplication of the CYP21A2 gene. This could affect the screening of individuals who are non known carriers. A person carrying a functional factor and a copy with a mutation on the aforementioned chromosome may be incorrectly labeled a carrier [i].

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Comeback of Affliction Resistance by Genetic Methods

Nicholas Andrew Robinson , ... Edwige Quillet , in Fish Diseases, 2017

ii.4.iii Gene Expression

Transcription of the cistron (conversion of Dna into RNA, or gene expression) is controlled in a temporal and spatial way so that the quantity of RNA produced by each factor varies depending on tissue type, cell type inside the same tissue, stage of development, or occurrence of environmental stressors. In this mode, the phenotype "disease resistance" is not but affected by the types and configuration of the proteins coded by genes, just also by where, when, and how much of each gene is transcribed and translated into protein. It is the interaction of all of these different quantities and types of proteins in different tissues and cell types at various stages of development, or in response to dissimilar stimuli, that determines the final phenotype. Because of this complexity at multiple levels, nosotros are still a long way from agreement the underlying mechanisms affecting disease resistance, or any other quantitative trait for that matter. However, there are some very constructive tools available for studying the simultaneous expression of genes in the genome, and when such approaches are combined with positional information for QTL, they can take u.s.a. closer to identifying the causative mutations affecting disease resistance.

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