Mechanism of crossing over

 Crossing over is a process in genetics by which the two chromosomes of a homologous pair exchange equal segments with each other. Crossing over occurs in the first division of meiosis. At that stage, each chromosome has replicated into two strands called sister chromatids. The two homologous chromosomes of a pair synapse or come together.\ While the chromosomes synapse, breaks occur at corresponding points in two of the non-sister chromatids, i.e., in one chromatid of each chromosome. Since the chromosomes are homologous, breaks at corresponding points mean that the segments that are broken off contain corresponding genes, i.e., alleles. The broken sections are then exchanged between the chromosomes to form complete new units, and each new recombined chromosome of the pair can go to a different daughter sex cell. Crossing over results in the recombination of genes found on the same chromosome, called linked genes, that would otherwise always be transmitted together.

1. Synapsis

During the zygotene stage of the first prophase of meiosis, the homologous (maternal and paternal) chromosomes start pairing and lie closely side by side. This phenomenon is called synapsis. Synapsis often starts with the attachment of ends of homologous chromosomes to the nuclear envelop and then pairing in a zipper-like fashion. By synapsis, the gene (or allele) on both the chromosomes are placed side by side (juxtaposition). This pairing of homologous chromosomes is brought about by the mutual attraction between the allelic genes. The paired chromosomes are known as bivalent. There are two theories that explain how two homologous chromosomes synapse or pair.

Precocity theory- This theory was proposed by C. D. Darlington in 1937. According to this theory, the chromosome enters meiosis in the form of a single chromatid (not bivalent). In terms of electrostatic interaction, this single chromatid is unbalanced or unsaturated. In order to become saturated or balanced, the chromosome must pair. This theory is not valid as it assumes the replication of chromosomes happens later in pachytene or diplotene. But it is observed and experimentally proved that the chromosome replicates before actual crossing over. Synaptonemal complex- A recent study reveals that synapsis and chiasma formation is facilitated by a highly organized structure of filaments called synaptonemal complex. Montrose J. Moses has revealed a highly organized structure of filaments called Synaptonemal complex in between the paired chromosomes of zygotene and pachytene stages. Refer meiosis chapter for more details.

2. Duplication of chromosome

Synapsis is followed by the duplication of chromosomes which change the bivalent nature of chromosome pair into tetravalent. During this, each of the homologous chromosomes in a bivalent split longitudinally into two sister chromatids attached to the undivided centromere. Thus, four chromatids are formed which remain side by side as two pairs. This should not be confused with DNA replication. The replication of genetic material already happens during the S phase of the interphase. But the replicated genetic material is held in a single chromatid and gets separated into two different chromatids in this stage.

3. Crossing over

In the pachytene stage crossing over takes place during which the non-sister chromatids of homologous pair twist over each other, the point of contact of cross over chromatids being called chiasma. In crossing, over two or three chromatids are involved, and accordingly, two or more chiasmata are formed. At each chiasma, the chromatid breaks, and the broken segment re-join to form a recombinant chromatid. Thus, the exchange of parts of chromatids brings about an alteration of the original sequence of genes in the chromosome. There are three theories that explain the process of crossing over.

Duplication theory

According to this theory, the crossing over happens during the duplication of chromosomes. The genes or genic region is visualized as beads or chromomeres and the non-genic region as interchromomeric region or linker. During replication of chromosomes, initially, the chromomeres are duplicated and the newly formed chromomeres remain tightly juxtaposed (side by) to the old ones.

When inter-chromomeric regions are synthesized to join these new genes or chromomeres, they may switch from a newly synthesized chromomere on the homologous chromosome to an adjacent chromomere of another homolog. This results in the formation of recombinations or cross-overs in a new set of chromatids.

Copy choice theory

This theory was proposed by Belling. This theory states that the entire recombinant section or part arises from the newly synthesized section. The non-sister chromatids when coming in close contact they copy some section of each other resulting in recombination. According to this theory, the physical exchange of preformed chromatids does not take place. The non-sister chromatids when coming together during pairing, copy parts of each other. Thus, recombinant chromosomes or chromatids have some alleles of one chromatid and some of the others. The information may be copied by one strand or both strands. When only one strand copies, nonreciprocal recombinant is produced.

If the copy process involves both strands of chromosomes, reciprocal recombinants are produced. Assume, there are two chromosomes, viz., AB and ab. When their chromatids come in close contact they copy each other and result in Ab and aB re-combinations besides parental combinations.

This theory has two objections

1. According to this theory breakage and reunion do not occur, while it has been observed cytologically.

2. Generally crossing over takes place after DNA replication but here it takes place at the same time.

Breakage and reunion theory

This theory states that crossing over takes place due to breakage and reunion of non-sister chromatids. The two segments of parental chromosomes which are present in recombinants arise from physical breaks in the parental chromosomes with the subsequent exchange of broken segments. The breakage and reunion are mediated by the enzymes endonuclease and ligase respectively. The broken ends of non-sister chromatids unite to produce chiasmata resulting in crossing over.

The breakage and reunion is again explained by three theories

i) Contact first theory (by Serebrovsky)- According to this theory the inner two chromatids of the homologous chromosomes undergoing crossing over first touch each other and then cross over. At

the point of contact, breakage occurs. The broken segments again unite to form new combinations.

ii) Breakage first theory (By Muller)- According to

In this theory, the chromatids under-going crossing over first of all break into two without any crossing over, and after that, the broken segments reunite to form the new combinations.

iii) Strain theory (by Darlington)- According to this theory the breakage in chromosomes or

chromatids are due to strain caused by pairing and later the breakage parts again reunite.

4. Chiasma terminalization

After crossing over is completed, the non-sister chromatids repel each other due to a lack of

attraction between them. The repulsion or separation of chromatids starts from the centromere

towards the end just like a zipper and this separation process is named terminalization. The

movement of chiasma away from the centromere and towards the end of tetrads is called

terminalization. The process of terminalization continues through diplotene, diakinesis and

ends in metaphase I. The total number of chiasmata terminalized at any given stage or time is

known as the coefficient of terminalization. Generally, chiasma terminalization occurs between

diplotene and metaphase I.

There are three theories to explain the mechanism of chiasma terminalization, viz:

i. Electrostatic hypothesis,

ii. Coiling hypothesis, and

iii. Elastic chromosome repulsion theory.

i. Electrostatic hypothesis- According to this hypothesis, terminalization takes place due to

localized repulsion force in centromere and generalized repulsion force on chromosome surface

during diplotene stage.

ii. Coiling hypothesis- According to this hypothesis, terminalization takes place by mechanical

tension developed within the chromosome due to coils. Thus, tension force becomes greater

than the force binding the chromatids at the point of exchange resulting in terminalization.

iii. Elastic chromosome repulsion- According to this theory, all bodies having a definite shape

resist any change that leads to alter their shapes. Chiasma forces the chromosome out of shape

by its binding force. This leads to the development of repulsion at the point of exchange

resulting in the terminalization of chiasma.

At the end of terminalization, the twisting chromatids separate so that the homologous

chromosomes are separated completely and move to opposite poles in Anaphase I. The crossing

over thus brings about an alteration of the linear sequence of genes in chromosomes that produce

gametes and thus add a new combination of character in progeny.