Recombination:

Homologous Recombination
 Contents
Recombination
Definition
Types
Crossing Over
Homologous Chromosomes
Homologous Recombination
History and Discovery
Significance in Eukaryotes, Bacteria and Viruses
Dysfunction in Homologous Recombination
Summary
References
 Recombination
Recombination is a process by which pieces of DNA
are broken and recombined to produce new
combinations of alleles.

It creates genetic diversity at the level of genes that

reflects differences in the DNA sequences of different
organisms.

During meiosis in eukaryotes, genetic recombination

involves the pairing of homologous chromosomes.
Recombination occurs randomly in nature as a normal
event of meiosis.

It is enhanced by the phenomenon of crossing over, in which

gene sequences called linkage groups are disrupted.

This disruption results in an exchange of segments between

paired chromosomes that are undergoing separation.

This justifies that meiosis results in daughter cells which are

not alike despite having half of the genetic material from the
parent.
 Types

1. Homologous recombination

2. Non homologous recombination

3. Site specific recombination

4. Replicative recombination
 Homologous
Recombination
 Homologous Chromosomes
Each diploid cell contains two copies of every
chromosome, one derived from the maternal gamete
and the other from the paternal gamete.

These pairs of chromosomes, each derived from one

parent, are called homologous chromosomes.
 Homologous Recombination
General recombination or Homologous recombination
ensures maintenance of genomic integrity. During
meiosis, Homologous recombination results in DNA
crossover events between homologous chromosomes that
produce the genetic diversity inherent in germ cells.

Accurate DNA replication and repair of DNA damage

are essential to maintaining genetic information and
ensuring its accurate transmission from parent to
offspring. From the standpoint of evolution, it is also
important to generate genetic diversity.
 Crossing Over
Crossing over is the exchange of genetic material
between non-sister chromatids of homologous
chromosomes during meiosis, which results in new
allelic combinations in the daughter cells.
History and Discovery
In early 1900s, William Bateson and Reginald Punnett found
that certain genes associated with physical traits can be
inherited together, or genetically linked.
In 1911, Thomas Hunt Morgan suggested that "crossovers"
can occur between linked genes, where one of the linked
genes physically crosses over to a different chromosome.
In 1930s Barbara McClintock and Harriet Creighton
demonstrated that chromosomal crossover occurs during
meiosis
Also in 1930s Curt Stern showed that crossing over—later
called "recombination"—could also occur in somatic cells
like white blood cells and skin cells that divide through
mitosis.
Cont.
In 1947, the microbiologist Joshua Lederberg showed that
bacteria are capable of genetic recombination, which is more
similar to sexual reproduction.
In 1964 Robin Holliday proposed a model for recombination in
meiosis which introduced key details of how the process can
work, including the exchange of material between
chromosomes through Holliday junctions.
In 1983, Jack Szostak and colleagues presented a model now
known as the DSBR pathway, which accounted for
observations not explained by the Holliday model.
In 1990s experiments in Drosophila, budding yeast and
mammalian cells led to the emergence of other models of
homologous recombination, called SDSA pathways, which do
not always rely on Holliday junctions.
 Significance in Eukaryotes
Homologous recombination is essential to cell division in
eukaryotes like plants, animals, fungi and protists.

In cells that divide through mitosis, homologous recombination

repairs double-strand breaks in DNA caused by ionizing
radiation or DNA-damaging chemicals. Left unrepaired, these
double-strand breaks can cause large-scale rearrangement of
chromosomes in somatic cells, which can in turn lead to cancer.

Homologous recombination also helps produce genetic diversity

through cross over between homologous chromosomes when cells
divide in meiosis to become specialized gamete cells—sperm or
egg cells in animals, pollen or ovules in plants, and spores in
fungi. This creates new, possibly beneficial combinations of
genes, which can give offspring an evolutionary advantage.
Cont.
In Eukaryotes chromosomal crossover often begins
when a protein called Spo11 makes a targeted
double-strand break in DNA.

These double-strand break sites often occur at

recombination hotspots, regions in chromosomes
that are about 1,000–2,000 base pairs in length and
have high rates of recombination.
 Significance in Bacteria
Homologous recombination is a major DNA repair process
in bacteria. It is also important for producing genetic
diversity in bacterial populations, although the process
differs substantially from meiotic recombination, which
repairs DNA damages and brings about diversity in
eukaryotic genomes.
Homologous recombination has been studied in
Escherichia coli in which two pathways were observed.
I. Double-strand DNA breaks are repaired by the RecBCD
pathway of homologous recombination.
II. Breaks that occur on only one of the two DNA strands,
known as single-strand gaps, are thought to be repaired
by the RecF pathway.
Cont.
Both the RecBCD and RecF pathways include a
series of reactions known as branch migration (in
which single DNA strands are exchanged between
two intercrossed molecules of duplex DNA) and
resolution (in which those two intercrossed
molecules of DNA are cut apart and restored to
their normal double-stranded state).
Significance in Viruses
Homologous recombination occurs in several
groups of viruses. In DNA viruses such as
herpesvirus, recombination occurs through a
break-and-rejoin mechanism like in bacteria and
eukaryotes.
There is also evidence for recombination in some
RNA viruses, specifically positive-sense ssRNA
viruses like retroviruses, picornaviruses, and
coronaviruses.
There is controversy over whether homologous
recombination occurs in negative-sense ssRNA
viruses like influenza.
Cont.

Homologous recombination is important in

facilitating viral evolution.

It is the proposed mechanism whereby the DNA

virus human herpesvirus-6 integrates into human
telomeres.
Multiplicity Reactivation

When two or more viruses, each containing lethal

genomic damage, infect the same host cell, the virus
genomes can often pair with each other and
undergo homologous recombination repair to
produce viable progeny. This is known as
Multiplicity reactivation
Dysfunction in Homologous
Recombination
Without proper homologous recombination,
chromosomes may incorrectly align for the first
phase of cell division in meiosis.

This causes failure to properly segregate resulting

in nondisjunction.

Nondisjunction can cause sperm and ova to have

too few or too many chromosomes e.g. Down's
syndrome.
Symptoms of Down’s syndrome
Cont.
Deficiencies in homologous recombination have
been strongly linked to cancer formation in
humans.

For example, each of the cancer-related diseases

Bloom's syndrome, Werner's syndrome and
Rothmund-Thomson syndrome are caused by
malfunctioning copies of RecQ helicase genes
involved in the regulation of homologous
recombination
Cont.
Decreased rates of homologous recombination
cause inefficient DNA repair which can also lead to
cancer eg. BRCA1 and BRCA2, two similar tumor
suppressor genes whose malfunctioning has been
linked with considerably increased risk for breast
and ovarian cancer.
Summary
General recombination (also called homologous
recombination) allows large sections of the DNA
double helix to move from one chromosome to
another, and it is responsible for the crossing-over
of chromosomes that occurs during meiosis in
fungi, animals, and plants.

General recombination is essential for the

maintenance of normal chromosome number in all
cells.
References
https://www.britannica.com/science/homologous-reco
mbination
https://en.wikipedia.org/wiki/Homologous_recombinat
ion
Pierce BA. 2017. Genetics: A conceptual approach. W.
H. Freeman & Cpmpany, USA, ISBN-10: 1319050964
Weaver, R. F., 2011 Molecular Biology 5th ed., ISBN:
9780073525327
 Thank You

Stay Home Stay Safe