Gene conversion is a genetic process where one DNA sequence replaces a homologous, or similar, sequence, making them identical. This event can be likened to a “copy and paste” function within the genome where a segment of DNA from a “donor” sequence is copied over a “recipient” sequence. The process is a non-reciprocal transfer of genetic information, meaning one sequence is changed while the other remains the same.
The Mechanism of Gene Conversion
Gene conversion is a frequent result of the cell’s machinery for repairing DNA, specifically a type of damage called a double-strand break (DSB). A DSB is a fracture across both strands of the DNA double helix. When this occurs, the cell initiates a repair process using a homologous DNA sequence as a template. This template can be from a sister chromatid or a homologous chromosome.
The repair mechanism begins with the 5′ ends of the broken DNA being degraded, which creates 3′ single-stranded tails. One of these tails then “invades” the intact homologous DNA template, creating a structure known as a D-loop. This invading strand acts as a primer for DNA synthesis, using the template strand to create a new stretch of DNA.
Once the new DNA is synthesized, the process can follow a couple of different paths. In a pathway known as synthesis-dependent strand annealing (SDSA), the newly synthesized strand is displaced from the template and anneals with the other side of the original break. Any remaining gaps are filled in, and the DNA strands are ligated, completing the repair. This process results in gene conversion without an exchange of the surrounding DNA.
Alternatively, the repair can proceed through a double Holliday junction pathway, which can lead to either gene conversion alone or with a crossover of the flanking DNA. The process can create regions of heteroduplex DNA, where the two strands of the DNA molecule come from different original sources. The cell’s mismatch repair system may then correct any mismatched base pairs within this region, solidifying the conversion.
Distinguishing Gene Conversion from Crossing Over
Gene conversion and crossing over are both outcomes of homologous recombination, but they represent different ways genetic information is exchanged. The primary distinction is that crossing over is a reciprocal process, meaning there is a mutual exchange of genetic material between two homologous chromosomes. This results in a new combination of genetic markers on each chromosome.
This reciprocal exchange during crossing over involves the physical swapping of large segments of chromosome arms. The result is that both participating chromosomes are altered, each now carrying a piece of the other. This process is a major source of genetic shuffling during meiosis, creating new combinations of alleles on chromosomes that are passed to the next generation.
In contrast, gene conversion is a non-reciprocal transfer of genetic information. One sequence acts as a donor, providing the genetic information, while the other acts as a recipient, having its sequence changed. The donor sequence itself is not physically altered in the process, and this one-way transfer involves shorter stretches of DNA.
Types of Gene Conversion
Gene conversion is categorized into two main types based on the relationship between the DNA sequences involved. The first, allelic gene conversion, happens between two different versions, or alleles, of the same gene located on a pair of homologous chromosomes. This form of conversion occurs during meiosis, the cell division that produces sperm and egg cells. If an individual has two different alleles for a particular gene, a mismatch can arise during recombination, and the cell’s repair machinery may then correct this mismatch by converting one allele into the other.
Ectopic gene conversion, also known as non-allelic conversion, takes place between two similar DNA sequences that are not at the same location in the genome. These sequences could be members of a gene family on different chromosomes or at distant locations on the same chromosome. This type of conversion can also occur between a functional gene and a pseudogene, which is a non-functional relative of a gene. Ectopic conversion is often initiated by DNA repair processes outside of meiosis.
Evolutionary and Functional Significance
Gene conversion has a multifaceted role in genetics, impacting evolution and human health. It serves as a mechanism for both generating genetic diversity and homogenizing sequences within gene families. By creating new combinations of genetic variations within a single gene, it can contribute to the pool of novel alleles in a population upon which natural selection can act.
In the context of gene families, ectopic gene conversion can lead to a phenomenon known as concerted evolution. This is a process where members of a gene family evolve together in a coordinated manner. Gene conversion can copy sequences from one family member to another, ensuring that the genes remain similar over evolutionary time. This is important for gene families that produce products in large quantities, such as ribosomal RNA genes, where functional uniformity is advantageous.
The process also has a direct impact on health and disease. It can be a beneficial DNA repair mechanism, correcting a harmful mutation by using a healthy allele as a template. Conversely, gene conversion can have detrimental effects by spreading a disease-causing mutation from one faulty gene copy to a functional one, leading to genetic disorders. For example, gene conversion is known to be a cause of mutations in the CYP21A2 gene, which can result in congenital adrenal hyperplasia.