CHROMOSOMAL CROSSOVER (or CROSSING OVER) is the exchange of genetic material between homologous chromosomes that results in recombinant chromosomes during sexual reproduction . 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.
Crossing over was described, in theory, by
Thomas Hunt Morgan
The linked frequency of crossing over between two gene loci (markers ) is the crossing-over value . For fixed set of genetic and environmental conditions, recombination in a particular region of a linkage structure (chromosome ) tends to be constant and the same is then true for the crossing-over value which is used in the production of genetic maps .
* 1 Origins
* 2 Chemistry
* 2.1 MSH4 and MSH5 * 2.2 Chiasma
* 3 Consequences * 4 Non-homologous crossover * 5 See also * 6 References
There are two popular and overlapping theories that explain the
origins of crossing-over, coming from the different theories on the
origin of meiosis . The first theory rests upon the idea that meiosis
evolved as another method of
DNA REPAIR THEORY
Crossing over and
LINKS TO BACTERIAL TRANSFORMATION
The process of bacterial transformation also shares many similarities
with chromosomal cross over, particularly in the formation of
overhangs on the sides of the broken DNA strand, allowing for the
annealing of a new strand.
Bacterial transformation itself has been
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 recombination may be initiated by double-stranded breaks that
are introduced into the DNA by exposure to DNA damaging agents or the
Spo11 protein. One or more exonucleases then digest the 5’ ends
generated by the double-stranded breaks to produce 3’
single-stranded DNA tails (see diagram). The meiosis-specific
Dmc1 and the general recombinase
Rad51 coat the
single-stranded DNA to form nucleoprotein filaments. The recombinases
catalyze invasion of the opposite chromatid by the single-stranded DNA
from one end of the break. Next, the 3’ end of the invading DNA
primes DNA synthesis, causing displacement of the complementary
strand, which subsequently anneals to the single-stranded DNA
generated from the other end of the initial double-stranded break. The
structure that results is a cross-strand exchange, also known as a
Molecular structure of a Holliday junction.
Molecular structure of a Holliday junction. From PDB : 3CRX.
MSH4 AND MSH5
The MSH4 and MSH5 proteins form a hetero-oligomeric structure (heterodimer ) in yeast and humans. In the yeast Saccharomyces cerevisiae MSH4 and MSH5 act specifically to facilitate crossovers between homologous chromosomes during meiosis . The MSH4/MSH5 complex binds and stabilizes double Holliday junctions and promotes their resolution into crossover products. An MSH4 hypomorphic (partially functional) mutant of S. cerevisiae showed a 30% genome wide reduction in crossover numbers, and a large number of meioses with non exchange chromosomes. Nevertheless, this mutant gave rise to spore viability patterns suggesting that segregation of non-exchange chromosomes occurred efficiently. Thus in S. cerevisiae proper segregation apparently does not entirely depend on crossovers between homologous pairs.
The grasshopper Melanoplus femur-rubrum was exposed to an acute dose of X-rays during each individual stage of meiosis , and chiasma frequency was measured. Irradiation during the leptotene -zygotene stages of meiosis (that is, prior to the pachytene period in which crossover recombination occurs) was found to increase subsequent chiasma frequency. Similarly, in the grasshopper Chorthippus brunneus , exposure to X-irradiation during the zygotene-early pachytene stages caused a significant increase in mean cell chiasma frequency. Chiasma frequency was scored at the later diplotene-diakinesis stages of meiosis. These results suggest that X-rays induce DNA damages that are repaired by a crossover pathway leading to chiasma formation.
The difference between gene conversion and CHROMOSOMAL CROSSOVER.
In most eukaryotes , a cell carries two versions of each gene , each referred to as an allele . Each parent passes on one allele to each offspring. An individual gamete inherits a complete haploid complement of alleles on chromosomes that are independently selected from each pair of chromatids lined up on the metaphase plate. Without recombination, all alleles for those genes linked together on the same chromosome would be inherited together. Meiotic recombination allows a more independent segregation between the two alleles that occupy the positions of single genes, as recombination shuffles the allele content between homologous chromosomes.
Recombination results in a new arrangement of maternal and paternal
alleles on the same chromosome. Although the same genes appear in the
same order, some alleles are different. In this way, it is
theoretically possible to have any combination of parental alleles in
an offspring, and the fact that two alleles appear together in one
offspring does not have any influence on the statistical probability
that another offspring will have the same combination. This principle
of "independent assortment " of genes is fundamental to genetic
inheritance. However, the frequency of recombination is actually not
the same for all gene combinations. This leads to the notion of
"genetic distance ", which is a measure of recombination frequency
averaged over a (suitably large) sample of pedigrees. Loosely
speaking, one may say that this is because recombination is greatly
influenced by the proximity of one gene to another. If two genes are
located close together on a chromosome, the likelihood that a
recombination event will separate these two genes is less than if they
were farther apart.
Genetic linkage describes the tendency of genes to
be inherited together as a result of their location on the same
Linkage disequilibrium describes a situation in which some
combinations of genes or genetic markers occur more or less frequently
in a population than would be expected from their distances apart.
This concept is applied when searching for a gene that may cause a
particular disease . This is done by comparing the occurrence of a
Crossovers typically occur between homologous regions of matching
chromosomes , but similarities in sequence and other factors can
result in mismatched alignments. Most DNA is composed of base pair
sequences repeated very large numbers of times. These repetitious
segments, often referred to as satellites, are fairly homogenous among
a species. During
The specific causes of non-homologous crossover events are unknown, but several influential factors are known to increase the likelihood of an unequal crossover. One common vector leading to unbalanced recombination is the repair of double-strand breaks (DSBs). DSBs are often repaired using non-homologous end joining, a process which involves invasion of a template strand by the DSB strand (see figure below). Nearby homologous regions of the template strand are often used for repair, which can give rise to either insertions or deletions in the genome if a non-homologous but complementary part of the template strand is used. Sequence similarity is a major player in crossover – crossover events are more likely to occur in long regions of close identity on a gene. This means that any section of the genome with long sections of repetitive DNA is prone to crossover events.
The presence of transposable elements is another influential element of non-homologous crossover. Repetitive regions of code characterize transposable elements; complementary but non-homologous regions are ubiquitous within transposons. Because chromosomal regions composed of transposons have large quantities of identical, repetitious code in a condensed space, it is thought that transposon regions undergoing a crossover event are more prone to erroneous complementary match-up; that is to say, a section of a chromosome containing a lot of identical sequences, should it undergo a crossover event, is less certain to match up with a perfectly homologous section of complementary code and more prone to binding with a section of code on a slightly different part of the chromosome. This results in unbalanced recombination, as genetic information may be either inserted or deleted into the new chromosome, depending on where the recombination occurred.
While the motivating factors behind unequal recombination remain obscure, elements of the physical mechanism have been elucidated. Mismatch repair (MMR) proteins, for instance, are a well-known regulatory family of proteins, responsible for regulating mismatched sequences of DNA during replication and escape regulation. The operative goal of MMRs is the restoration of the parental genotype. One class of MMR in particular, MutSβ, is known to initiate the correction of insertion-deletion mismatches of up to 16 nucleotides. Little is known about the excision process in eukaryotes, but E. coli excisions involve the cleaving of a nick on either the 5’ or 3’ strand, after which DNA helicase and DNA polymerase III bind and generate single-stranded proteins, which are digested by exonucleases and attached to the strand by ligase . Multiple MMR pathways have been implicated in the maintenance of complex organism genome stability, and any of many possible malfunctions in the MMR pathway result in DNA editing and correction errors. Therefore, while it is not certain precisely what mechanisms lead to errors of non-homologous crossover, it is extremely likely that the MMR pathway is involved.
* ^ Griffiths, AJF; Gelbart, WM; Miller, JH; et al. (1999). "Modern
Genetic Analysis: Mitotic Crossing-Over". New York: W. H. Freeman.
* ^ Creighton H, McClintock B (1931). "A Correlation of Cytological
and Genetical Crossing-Over in Zea Mays" . Proc Natl Acad Sci USA. 17
(8): 492–7. PMC 1076098 . PMID 16587654 . doi
:10.1073/pnas.17.8.492 . (Original paper)
* ^ Rieger R. Michaelis A., Green M. M. (1976). Glossary of
genetics and cytogenetics: Classical and molecular. Heidelberg - New
York: Springer-Verlag. ISBN 3-540-07668-9 . CS1 maint: Uses authors
parameter (link )
* ^ King R. C., Stransfield W. D. (1998): Dictionary of genetics.
Oxford University Press, New York, Oxford, ISBN 0-19-50944-1-7 ; ISBN
* ^ A B C D E Harris Bernstein, Carol Bernstein and Richard E.
* v * t * e
* Conjugation * Transduction * Transformation
OCCURS IN EUKARYOTES