Homologous recombination

Homologous recombination is a form of genetic recombination in which genetic material is exchanged between two strands of DNA with similar or identical base sequences. It is a naturally occurring phenomenon in eukaryotes, bacteria, and some viruses. Homologous recombination occurs during meiosis in eukaryotes. Within these organisms, it plays an important role in repairing harmful double-strand breaks in DNA and allowing genetic material to be shuffled during meiosis in order to create new combinations of DNA sequences. Similarly, homologous recombination is also crucial to DNA repair and helps to incorporate genetic material received through horizontal gene transfer and transformation into DNA in bacteria. Homologous recombination also plays a critical role in shaping the evolution of certain viruses. Homologous recombination is a useful mechanism in genetic engineering as well. In this context, it is often utilized by genetic engineers as a tool for gene targeting, which is when an engineered mutation is inserted into a particular gene so that the function of the gene in question can be studied.

Background

Homologous recombination is a process associated with genetics and DNA. DNA, or deoxyribonucleic acid, is a hereditary material that contains the genes that serve as the building blocks of all living organisms. Human genes are the strings found on chromosomes located in cell nuclei. Each strand of DNA includes twenty-three pairs of chromosomes, half of which are inherited from a person’s mother and half of which come from a person’s father.

One of the most important mechanisms in genetics is recombination. Genetic recombination occurs when genetic material is exchanged between either two chromosomes or two separate regions within a single chromosome. This process happens in both eukaryotes, which are organisms made of cells that have chromosomes located inside a distinct nucleus, and prokaryotes, which are single-celled organisms like bacteria that do not have a distinct nucleus. In eukaryotes, recombination occurs during meiosis, the process by which gametes, or sex cells, are produced. Before meiosis begins, the chromosomes in a diploid cell, which is a cell that has two complete sets of chromosomes, undergo DNA replication.

This results in the production of identical sister chromatids, or threadlike strands that each contain a double helix of DNA. As meiosis begins, two homologous chromosomes connect to form a new structure called a tetrad. The chromosomes in the tetrad then swap segments of DNA and are reconnected in a cross pattern. This process, known as recombination or crossover, ultimately yields DNA with both maternal and paternal segments. Once meiosis is complete, each diploid cell produces four new gametes with half the chromosome number and a unique recombination of genetic material from the original starting cell. This eventually allows for the creation of a new cell with forty-six total chromosomes when a twenty-three-chromosome sperm cell and a twenty-three-chromosome sperm cell meet at fertilization. Because the exchange of genetic material that takes place during DNA recombination is random, the process itself also serves to increase genetic variability.

While genetic recombination mostly happens during meiosis, it sometimes also occurs during connection mitosis, especially in prokaryotes. Mitosis is a form of cell division in which two daughter cells with the same number and type of chromosomes as the parent nucleus are produced. Miotic recombination occurs during the interphase portion of mitosis that serves as the resting period between divisions. Prokaryotic recombination takes place through three possible processes, including conjugation, transformation, and transduction. In conjugation, genes are donated from one organism to another when the two come into contact. In transformation, an organism gains new genes by acquiring DNA from the surrounding environment. In transduction, genes are transferred through a process mediated by viruses.

There are three broad types of genetic recombination. These include homologous, nonhomologous, and site-specific recombination. Homologous recombination takes place between DNA molecules with similar sequences. Nonhomologous recombination takes place between DNA molecules that are either not similar or only partly similar. Site-specific recombination takes place between certain short DNA sequences, often with at least some similarities.

Overview

Homologous recombination is a type of genetic recombination in which genetic material is exchanged between two similar strands of DNA. Also commonly known as general recombination, this process serves several important functions, most notably in relation to reproduction, DNA repair, and genetic engineering. It occurs in eukaryotes, prokaryotes, and viruses.

In eukaryotes, cells found in humans and other animals, one of homologous recombination’s most important functions is the role it plays in meiosis. Meiosis is the process through which the body produces the genetic material required for reproduction. The end product of meiosis is the sets of haploid chromosomes found in sperm and egg cells. These haploid chromosomes contain half of a person’s genetic material. When fertilization occurs, one person’s haploid chromosomes are joined with another person’s haploid chromosomes to create a full set of DNA that serves as the genetic blueprint for a new organism. Homologous recombination is essential to this process because it provides for added genetic variation. During the process of genetic recombination, the original DNA is shuffled rather than simply split in half. This yields a new set of haploid chromosomes that are unique from the original DNA. Similarly, homologous recombination also facilitates genetic diversity in sexual reproduction. The genetic recombination that occurs when separate haploid chromosomes from an egg and sperm cell join together and make a new organism that is different in various ways from either parent. In the event that this sort of homologous recombination goes awry in some way, new genetic traits can potentially emerge as well. This is why different children born to the same parents are not usually identical.

Homologous recombination also aids in DNA repair. DNA strands can sometimes suffer damage that would result in mutations in the genome or other serious consequences if it could not be repaired. The most common cause of damage to DNA strands is exposure to ionizing radiation or certain chemicals. When this type of damage occurs, the affected DNA strand undergoes homologous recombination in order to repair itself.

Homologous recombination has several special functions in bacteria and viruses. In bacteria, it plays a key role in the processes of horizontal gene transfer and bacterial transformation. Horizontal gene transfer is a genetic process through which foreign DNA from one organism is transferred into another without the two being related. When DNA transmitted from one organism is similar to the DNA of the organism receiving it, the separate pairs undergo homologous recombination so that the incoming DNA can be incorporated into the existing DNA. In bacterial transformation, DNA is transferred between different organisms of the same species. When this happens, both organisms undergo homologous recombination so that the donor DNA can bind to several proteins and thereby be incorporated into the receiver DNA. Homologous recombination promotes genetic diversity and aids in DNA repair in bacteria as well. In viruses, homologous recombination contributes to viral evolution when different viral genomes with detrimental mutations come together to create a new virus with a more advantageous genome. SARS-Cov-2, the virus that causes COVID-19, is a direct result of viral evolution via homologous recombination.

Homologous Recombination and Genetic Engineering

Homologous recombination is a useful tool in the field of genetic engineering. Genetic engineers use homologous recombination to target specific parts of the genome for modification. In practice, homologous recombination is used to “knock out” or remove genes that are defective or mutated. This is done by introducing the mutated gene into a cell where the foreign gene is matched with a native gene having a similar sequence. The two genes then undergo homologous recombination, which knocks out the mutated gene and produces a fully functional gene.

Homologous Recombination Deficiency

The role that homologous recombination plays in repairing damaged DNA is critical to an organism’s health. A cell that loses the ability to repair double-stranded breaks is said to have a condition known as Homologous Recombination Deficiency (HRD). HRD arises when the genes that control the repair process via homologous recombination develop mutations that change their protein’s functions such that they are left unable to repair damaged DNA. While cells can compensate for this to some degree, the resulting DNA ends up being repaired incorrectly. This may lead to scarring that can contribute to the development of certain cancers, including ovarian, breast, prostate, and pancreatic cancers. Issues with proper homologous recombination can also lead to other genetic anomalies, such as Down syndrome.

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