Crossover interference

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Crossover interference is the term used to refer to the non-random placement of crossovers with respect to each other during meiosis. The term is attributed to Hermann Joseph Muller, who observed that one crossover "interferes with the coincident occurrence of another crossing over in the same pair of chromosomes, and I have accordingly termed this phenomenon ‘interference’." [1]

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A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type. Homologous Recombination.jpg
A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.

Meiotic crossovers (COs) appear to be regulated to ensure that COs on the same chromosome are distributed far apart (crossover interference). In the nematode worm Caenorhabditis elegans , meiotic double-strand breaks (DSBs) outnumber COs. Thus not all DSBs are repaired by a recombination process(es) leading to COs. The RTEL-1 protein is required to prevent excess meiotic COs. In rtel-1 mutants meiotic CO recombination is significantly increased and crossover interference appears to be absent. [2] RTEL1 likely acts by promoting synthesis-dependent strand annealing which results in non-crossover (NCO) recombinants instead of COs (see diagram). [2] Normally, about half of all DSBs are converted into NCOs. RTEL-1 appears to enforce meiotic crossover interference by directing the repair of some DSBs towards NCOs rather than COs. [2]

In humans, recombination rate increases with maternal age. [3] Furthermore, placement of female recombination events appears to become increasingly deregulated with maternal age, with a larger fraction of events occurring within closer proximity to each other than would be expected under simple models of crossover interference. [4]

High negative interference

Bacteriophage T4

High negative interference (HNI), in contrast to positive interference, refers to the association of recombination events ordinarily measured over short genomic distances, usually within a gene. Over such short distances there is a positive correlation (negative interference) of recombinational events. As studied in bacteriophage T4 this correlation is greater the shorter the interval between the sites used for detection. [5] HNI is due to multiple exchanges within a short region of the genome during an individual mating event. [6] What is counted as a “single exchange” in a genetic cross involving only distant markers may in reality be a complex event that is distributed over a finite region of the genome. [7] Switching between template DNA strands during DNA synthesis (see Figure, SDSA pathway), referred to as copy-choice recombination, was proposed to explain the positive correlation of recombination events within the gene. [8] HNI appears to require fairly precise base complementarity in the regions of the parental genomes where the associated recombination events occur. [9]

HIV

Each human immunodeficiency virus (HIV) particle contains two single-stranded positive sense RNA genomes. After infection of a host cell, a DNA copy of the genome is formed by reverse transcription of the RNA genomes. Reverse transcription is accompanied by template switching between the two RNA genome copies (copy-choice recombination). [10] From 5 to 14 recombination events per genome occur at each replication cycle. [11] This recombination exhibits HNI. [12] HNI is apparently caused by correlated template switches during minus-strand DNA synthesis. [13] Template switching recombination appears to be necessary for maintaining genome integrity and as a repair mechanism for salvaging damaged genomes. [10] [14]

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Chromosomal crossover Cellular process

Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.

Genetic recombination Production of offspring with combinations of traits that differ from those found in either parent

Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be passed on from the parents to the offspring. Most recombination is naturally occurring.

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Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. In other words, the nearer two genes are on a chromosome, the lower the chance of recombination between them, and the more likely they are to be inherited together. Markers on different chromosomes are perfectly unlinked.

Helicase Class of enzymes to unpack an organisms genes

Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genes. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands such as DNA and RNA, using energy from ATP hydrolysis. There are many helicases, representing the great variety of processes in which strand separation must be catalyzed. Approximately 1% of eukaryotic genes code for helicases. The human genome codes for 95 non-redundant helicases: 64 RNA helicases and 31 DNA helicases. Many cellular processes, such as DNA replication, transcription, translation, recombination, DNA repair, and ribosome biogenesis involve the separation of nucleic acid strands that necessitates the use of helicases.

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Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids. It is widely used by cells to accurately repair harmful breaks that occur on both strands of DNA, known as double-strand breaks (DSB), in a process called homologous recombinational repair (HRR). Homologous recombination also produces new combinations of DNA sequences during meiosis, the process by which eukaryotes make gamete cells, like sperm and egg cells in animals. These new combinations of DNA represent genetic variation in offspring, which in turn enables populations to adapt during the course of evolution. Homologous recombination is also used in horizontal gene transfer to exchange genetic material between different strains and species of bacteria and viruses.

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Chiasma (genetics)

In genetics, a chiasma is the point of contact, the physical link, between two (non-sister) chromatids belonging to homologous chromosomes. At a given chiasma, an exchange of genetic material can occur between both chromatids, what is called a chromosomal crossover, but this is much more frequent during meiosis than mitosis. In meiosis, absence of a chiasma generally results in improper chromosomal segregation and aneuploidy.

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Synthesis-dependent strand annealing

Synthesis-dependent strand annealing (SDSA) is a major mechanism of homology-directed repair of DNA double-strand breaks (DSBs). Although many of the features of SDSA were first suggested in 1976, the double-Holliday junction model proposed in 1983 was favored by many researchers. In 1994, studies of double-strand gap repair in Drosophila were found to be incompatible with the double-Holliday junction model, leading researchers to propose a model they called synthesis-dependent strand annealing. Subsequent studies of meiotic recombination in S. cerevisiae found that non-crossover products appear earlier than double-Holliday junctions or crossover products, challenging the previous notion that both crossover and non-crossover products are produced by double-Holliday junctions and leading the authors to propose that non-crossover products are generated through SDSA.

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References

  1. Muller, H.J. (1916). "The mechanism of crossing over". Am. Nat. 50.
  2. 1 2 3 Youds JL, Mets DG, McIlwraith MJ, Martin JS, Ward JD, ONeil NJ, Rose AM, West SC, Meyer BJ, Boulton SJ (2010). "RTEL-1 enforces meiotic crossover interference and homeostasis". Science. 327 (5970): 1254–8. doi:10.1126/science.1183112. PMC   4770885 . PMID   20203049.
  3. Kong A, Barnard J, Gudbjartsson DF, Thorleifsson G, Jonsdottir G, Sigurdardottir S, Richardsson B, Jonsdottir J, Thorgeirsson T, Frigge ML, Lamb NE, Sherman S, Gulcher JR, Stefansson K (2004). "Recombination rate and reproductive success in humans". Nat. Genet. 36 (11): 1203–6. doi: 10.1038/ng1445 . PMID   15467721.
  4. Campbell CL, Furlotte NA, Eriksson N, Hinds D, Auton A (2015). "Escape from crossover interference increases with maternal age". Nat Commun. 6: 6260. doi:10.1038/ncomms7260. PMC   4335350 . PMID   25695863.
  5. Chase M, Doermann AH. High Negative Interference over Short Segments of the Genetic Structure of Bacteriophage T4. Genetics. 1958 May;43(3):332-53. PMID 17247760
  6. Edgar RS, Steinberg CM. On the origin of high negative interference over short segments of the genetic structure of bacteriophage T4. Virology. 1958 Aug;6(1):115-28. PMID 13626191
  7. Steinberg CM, Edgar RS.A critical test of a current theory of genetic recombination in bacteriophage. Genetics. 1962 Feb;47:187-208. PMID 13916671 PMCID:PMC1210322
  8. Bernstein H. On the mechanism of intragenic recombination. I. The rII region of bacteriophage T4. (1962) Journal of Theoretical Biology. 1962; 3, 335-353. https://doi.org/10.1016/S0022-5193(62)80030-7
  9. Berger H, Warren AJ. Effects of deletion mutations on high negative interference in T4D bacteriophage. Genetics. 1969 Sep;63(1):1-5. PMID 5365292 PMCID:PMC1212323
  10. 1 2 Rawson JMO, Nikolaitchik OA, Keele BF, Pathak VK, Hu WS. Recombination is required for efficient HIV-1 replication and the maintenance of viral genome integrity. Nucleic Acids Res. 2018 Nov 16;46(20):10535-10545. doi: 10.1093/nar/gky910. PMID 30307534
  11. Cromer D, Grimm AJ, Schlub TE, Mak J, Davenport MP. Estimating the in-vivo HIV template switching and recombination rate. AIDS. 2016 Jan;30(2):185-92. Doi: 10.1097/QAD.0000000000000936. PMID 26691546
  12. Hu WS, Bowman EH, Delviks KA, Pathak VK. Homologous recombination occurs in a distinct retroviral subpopulation and exhibits high negative interference. J Virol. 1997 Aug;71(8):6028-36. PMID 9223494
  13. Anderson JA, Teufel RJ 2nd, Yin PD, Hu WS. Correlated template-switching events during minus-strand DNA synthesis: a mechanism for high negative interference during retroviral recombination. J Virol. 1998 Feb;72(2):1186-94. PMID 9445017
  14. Hu WS, Temin HM. Retroviral recombination and reverse transcription. Science. 1990 Nov 30;250(4985):1227-33. PMID 1700865