Chromosomal Crossover

Let us know about Chromosomal Crossover. Chromosomal crossover , or crossing over , is the exchange of genetic material during sexual reproduction between non-sister chromatids of two homologous chromosomes , resulting in recombinant chromosomes . It is one of the last steps of genetic recombination , which occurs in the pachytene stage of prophase I during a process called meiosis synapsis . Synapsis begins before the synaptonemal complexdevelops and is not completed by the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break off and then attach to another chromosome.

Chromosomal Crossover

Crossing over occurs between prophase I and metaphase I and is the process where two homologous non-sister chromatids join with each other and two recombinant chromosomes exchange different segments of genetic material to form sister chromatids . It can also occur during mitosis, [1] resulting in loss of heterozygosity. Crossing over is essential for the normal separation of chromosomes during meiosis. [ citation needed ] Crossing over is also responsible for genetic variation, because of the exchange of genetic material during crossing over, the chromatids held together by the centromere .are no longer identical. Therefore, when chromosomes move and separate at meiosis II, some daughter cells receive daughter chromosomes with the recombinant allele. Because of this genetic recombination, offspring have a different set of alleles and genes than their parents. In the diagram, genes B and B are crossed with each other, forming the resulting recombinants after meiosis AB, AB, AB and AB.

The crossing over is described, in principle, by Thomas Hunt Morgan . He relied on the discovery of Frans Alphonse Janssens , who described the phenomenon in 1909 and called it “chiasmatypi”. [2] The term chiasm has been associated with chromosomal crossover, if not identical. Morgan immediately saw the great importance of Janssens’ cytological interpretation of Chiasmata to the experimental results of his research on the heredity of Drosophila . The physical basis of crossing over was first demonstrated in 1931 by Harriet Creighton and Barbara McClintock . [3]

The linked frequency of crossing over between two gene loci ( marker ) is the crossing-over value . For certain sets of genetic and environmental conditions, recombination becomes stable in a particular region of a linkage structure ( chromosome ) and the same is true for crossing-over values ​​that are used in the production of genetic maps .


There are two popular and overlapping theories that explain the origin of meiosis, which come from different theories on the origin of meiosis . The first theory rests on the idea that meiosis has evolved as another method of DNA repair , and thus crossing-over is a new way to replace potentially damaged sections of DNA. [ citation needed ] The second theory comes from the idea that meiosis evolved from bacterial change with the function of spreading diversity. [6]In 1931, Barbara McClintock discovered a triploid maize plant. They made important conclusions about the karyotype of corn, including the size and shape of the chromosomes. McClintock used the prophase and metaphase stages of mitosis to describe the morphology of corn chromosomes, and later showed the first cytological demonstration of crossing over in meiosis. Working with student Harriet Creighton, McClintock also made important contributions to the early understanding of the codependency of linked genes.

DNA Repair Principle

To know about Chromosomal Crossover, now we will know about DNA Repair Principle. Crossing over and DNA repair are very similar processes, using many of the same protein complexes. [7] [8]In his report, “The Signification of Response to the Genome to Challenge,” McClintock studied corn to show how the corn genome would alter itself to address threats to its existence. She used 450 self-pollinated plants that received a chromosome from each parent with a broken end. He used modified patterns of gene expression on different regions of the leaves of his corn plants to show that transposable elements (“controlling elements”) are hidden in the genome, and that their dynamics allows them to interact with genes at different loci. Allows the action to be changed. These elements can reorganize the genome by anywhere from a few nucleotides to an entire segment of a chromosome. Recombination and primase form the foundation of nucleotides along the DNA sequence. A special protein complex conserved between processesThere is RAD51 , a well-conserved recombinase protein that has been shown to be important in DNA repair as well as cross over. [9] D. melanogaster have also been linked to both processes, showing that mutants at these specific loci cannot repair or cross-link DNA. Such genes include mei-41, mei-9, hdm, spnA and brca2. [ citation needed ] This large group of conserved genes between processes supports the theory of a close evolutionary relationship. In addition, DNA repair and crossover have been found to favor similar regions on chromosomes. Wheat ( Triticum aestivum L.) In an experiment using radiation hybrid mapping on the 3b chromosome, crossing over and DNA repair were found to be predominantly in the same region. [10] Furthermore, crossing over has been correlated in response to stressful, and potential DNA damage, conditions.

link to bacterial transformation

The process of bacterial transformation shares many similarities with chromosomal cross over, in particular the formation of overhangs at the edges of a broken DNA strand, allowing the annealing of a new strand. Bacterial transformation has been linked to DNA repair several times. citation needed ] The second theory comes from the idea that meiosis evolved from bacterial transformation, with the function of spreading genetic diversity. [6] . [13]Thus, this evidence suggests that it is a question of whether the crossover is associated with DNA repair or bacterial transformation, as the two are not mutually exclusive. It is likely that crossing over may have evolved from bacterial transformation, which in turn evolved from DNA repair, thus explaining the link between all three processes.


Meiotic recombination can be initiated by double-stranded breaks introduced into DNA by exposure to DNA- damaging agents, or the Spo11 protein. [14] One or more exonucleases then digest the 5′ ends to produce the 3′ single stranded DNA tail (see picture) generated by double-thread breaks. Meiosis-specific recombinase Dmc1 and general recombinase Rad51 coat single-stranded DNA to form nucleoprotein filaments. [15]Recombination catalyzes the invasion of the opposite chromatid by single-stranded DNA from one end of the break. Subsequently, the 3′ end of the invading DNA provokes DNA synthesis, leading to displacement of the complementary strand, which subsequently cleaves the single-stranded DNA generated from the other end of the initial double-stranded break. The resulting structure is a cross-strand exchange , also known as a Holliday junction. The contact between two chromatids that will soon undergo cross-over is known as a chiasma . The Holliday junction is a tetrahedral structure that can be ‘pulled’ by other recombination, taking it along a four-stranded structure.

Chromosomal Crossover
Chromosomal Crossover: Chromosomal Crossover
  • The molecular structure of the Holiday junction.
Chromosomal Crossover: The molecular structure of the Holiday junction. From PDB : 3CRX .

MSH4 and MSH5

The MSH4 and MSH5 proteins form a hetero-oligomeric structure (heterodimer) in yeast and humans. [16] [17] [18] In yeast Saccharomyces cerevisiae MSH4 and MSH5 function specifically to facilitate crossover between homologous chromosomes during meiosis. [16] The MSH4/MSH5 complex binds and stabilizes double Holiday 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 number and a large number of meiosis with non-exchange chromosomes. [19]Nevertheless, this mutant gave rise to a spore viability pattern suggesting that the segregation of non-exchange chromosomes occurred efficiently. Thus s. cerevisiae apparently does not entirely depend on crossover between homozygous pairs.


The grasshopper Melanoplus femur-rubrum was exposed to an acute dose of X-rays during each individual phase of meiosis, and chiasm frequency was measured. [20] Irradiation during the leptotene-zygotene stages of meiosis (that is, the pachytene period prior to which crossover recombination occurs) was found to increase later chiasma frequency. Similarly, in the locust Corthipus brunus , exposure to X-radiation during the zygotene -early pachytene stages resulted in a significant increase in mean cell chiasm frequency. [21]Chiasma frequency was scored at the later diplotene–diakinesis stages of meiosis. These results suggest that X-rays induce DNA damage that is repaired by a crossover pathway leading to the formation of chiasm.


In most eukaryotes, there are two versions of each gene in a cell, each called an allele. Each parent passes 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 of those genes linked together on the same chromosome would be inherited together. Meiotic recombination allows a more independent segregation between two alleles that occupy the position of a single gene, as recombination shuffles the allele material 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 sequence, some alleles differ. 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 has no effect on the statistical probability that another offspring will have alleles. There will be only one combination. This principle of “independent classification” of genes is fundamental to genetic inheritance. [22]However, the frequency of recombination is not actually the same for all gene combinations. This leads to the notion of “genetic distance”, which is a measure of recombination frequency over the average of a (suitably large) sample of pedigrees. In short, one can 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, there is a possibility that a recombination event would separate these two genes than if they were far apart. Genetic linkage describes the tendency of genes to be inherited together as a result of their location on the same chromosome. Linkage disequilibrium describes a condition in which certain combinations of genes or genetic markers occur more or less frequently in a population, which are expected to be separated by their distances. This concept is applicable when searching for a gene that may be the cause of a particular disease. This is done by comparing the occurrence of a specific DNA sequence with the presence of a disease. When a high correlation is found between the two, it is likely that the appropriate gene sequence is indeed close.

non-uniform crossover

To know about Chromosomal Crossover, now know about non-uniform crossover. Crossovers usually occur between homologous regions of matching chromosomes, but similarity in sequence and other factors can result in mismatched alignments. Most DNA is made up of base pair sequences that are repeated in very large numbers. [24] These repetitive segments, often called satellites, are fairly homologous between species. [24] During DNA replication, each strand of DNA is used as a template for the construction of a new strand using a partially conserved mechanism; If this process works properly, two identical, paired chromosomes are formed, often called sisters. Sister chromatid crossover events are known to occur at the rate of several crossover events per cell per cell in eukaryotes. [24]Most of these events involve the exchange of genetic information in equal amounts, but sequence mismatches can lead to unequal exchanges. These are referred to by various names, including non-homologous crossovers, unequal crossovers and unbalanced recombination, and result from the insertion or deletion of genetic information into a chromosome. While rare compared to homozygous crossover events, these mutations are hardwired, affecting multiple loci at the same time. They are considered to be the main driver behind the generation of gene duplications and are a common source of mutations within the genome. [25]

The specific causes of non-uniform crossover events are unknown, but several influencing factors are known to increase the likelihood of an unequal crossover. A common vector leading to unbalanced recombination is double-strand break (DSB) repair. [26] DSBs are often repaired using homology directed repair, a process that involves invasion of the template strand by the DSB strand (see figure below). Homologous regions around the template strand are often used for repair, which can lead to insertions or deletions in the genome if a non-homologous but complementary part of the template strand is used. [26] Sequence similarity is a major player in crossover – crossover events are more likely to occur in long regions of close identity on genes. [27]This means that any segment of the genome that contains long segments of repetitive DNA is prone to crossover events.

Another impressive element of the non-uniform crossover is the presence of transposable elements. Repetitive regions of the code characterize transposable elements; Complementary but non-homologous regions are ubiquitous within the transposon. Since chromosomal regions composed of transposons contain large amounts of identical, repetitive codons in a condensed locus, it is thought that transposon regions undergoing crossover events are more prone to false complementary match-ups; [28]That is, a segment of chromosome that contains lots of identical sequences, should it undergo a crossover event, is less certain to coincide with a completely homologous segment of the complementary code and more prone to binding with a segment The code is on a slightly different part of the chromosome. This results in unbalanced recombination, as genetic information may be inserted or deleted into the new chromosome, depending on the location of the recombination.

While the driving factors behind unequal recombination remain unclear, elements of the physical mechanism have been elucidated. For example, mismatch repair (MMR) proteins, a well-known regulatory family of proteins, are responsible for regulating DNA mismatch sequences during regulation of replication and migration. [29] The active goal of MMR is the restoration of parental genotypes. One class of MMRs, in particular, MutSβ, is known to initiate the correction of insertion–deletion mismatches of 16 nucleotides. [29] Little is known about the process of excision in eukaryotes, but E. coliExcision involves cleaving a nick on the 5′ or 3′ strand, after which DNA helicase and DNA polymerase III bind to and generate single-stranded proteins, which are digested by exonucleases and ligases attached to the strand. [29] Several MMR pathways have been implicated in the maintenance of complex organismal genome stability, and several potential malfunctions in the MMR pathway result in DNA editing and correction errors. [30] Therefore, although it is not certain which mechanisms lead to errors of nonlinear crossover, it is highly likely that the MMR pathway is involved.