7.10
Conversión genética
Además de mantener la estabilidad del genoma mediante la reparación del ADN, la recombinación homóloga desempeña un papel importante en la diversifica…
A diferencia de la mitosis, en la que las roturas de doble cadena son accidentales, en la meiosis, son creadas por una enzima llamada Spo11, que escinde la columna vertebral del fosfodiéster. Los extremos helicoidales rotos son recortados por un complejo de proteínas llamado MRX y el daño se repara mediante un proceso llamado conversión de genes.
Aquí, la hebra de ADN "aceptora" dañada invade un dúplex de ADN "donante" homólogo para formar un bucle de desplazamiento. Esto crea regiones de ADN heterodúplex donde una hebra del ADN del donante se empareja con una hebra complementaria del ADN aceptor.
La ADN polimerasa extiende la hebra invasora, y el bucle D extendido luego se empareja con la cola 3' libre. La síntesis de ADN en la hebra recién capturada da como resultado la formación de un intermediario con dos estructuras de cuatro hebras llamadas uniones de Holliday.
Este intermedio de doble unión de Holliday se resuelve mediante enzimas reparadoras del ADN llamadas resolvasas y hay dos orientaciones en las que se pueden escindir las uniones. En el primero, la resolvasa corta cada unión horizontalmente para que las hebras parentales aún estén intactas.
Esto da como resultado un producto no cruzado, llamado así porque las hebras después de la rotura permanecen con su compañero original, y no hay un cruce importante de las hebras donante y aceptora.
Alternativamente, si la escisión ocurre verticalmente, las regiones que flanquean el daño se intercambian, lo que conduce a un producto cruzado, donde la hebra donante después de la ruptura se recombina con la hebra aceptora.
La conversión génica tiene un impacto significativo en la diversidad genómica. En los organismos que se reproducen sexualmente, la descendencia hereda un conjunto de genes del padre y otro de la madre.
Los conjuntos de ADN parental se recombinan y las cromátidas hermanas se someten a una conversión génica. Esto da como resultado que la descendencia tenga cromosomas nuevos en comparación con los de los padres.
Q1: How does gene conversion repair double-strand breaks during meiosis?
Gene conversion repairs double-strand breaks created by Spo11 enzyme during meiosis. The damaged acceptor DNA strand invades a homologous donor DNA duplex, forming a displacement loop. DNA polymerase extends the invading strand, creating heteroduplex DNA regions where donor and acceptor strands pair. This process ultimately resolves into either crossover or non-crossover products through Holliday junction cleavage.
Q2: What are Holliday junctions and how are they resolved?
Holliday junctions are four-strand DNA structures formed during gene conversion when the extended D-loop pairs with the free 3' tail. Two Holliday junctions create an intermediate structure that resolvase enzymes cleave in two possible orientations. Horizontal cleavage produces non-crossover products where parental strands remain intact, while vertical cleavage generates crossover products with recombined donor and acceptor strands.
Q3: What is the difference between crossover and non-crossover products in gene conversion?
Non-crossover products result from horizontal Holliday junction cleavage, keeping parental strands with their original partners without major strand exchange. Crossover products arise from vertical cleavage, causing regions flanking the damage to switch, so donor strands recombine with acceptor strands. Both outcomes contribute to genomic diversity but through different recombination patterns.
Q4: How does gene conversion contribute to genomic diversity in offspring?
Gene conversion increases genomic diversity by recombining parental DNA sets during meiosis. Offspring inherit one gene set from each parent, and sister chromatids undergo gene conversion, creating novel chromosomes different from either parent. This recombination of sequences forms the molecular basis of genomic evolution, generating new amalgamated sequences that determine cell fitness and survival.
Q5: What role do the MRX protein complex and Spo11 enzyme play in gene conversion?
Spo11 enzyme deliberately creates double-strand breaks during meiosis by cleaving the phosphodiester backbone, unlike accidental breaks in mitosis. The MRX protein complex then trims the broken helical ends, preparing them for repair. Together, these proteins initiate the gene conversion process that repairs damage while promoting genetic recombination and diversity.
Q6: What is heteroduplex DNA and how does it form during gene conversion?
Heteroduplex DNA forms when a strand from donor DNA pairs with a complementary strand from acceptor DNA during gene conversion. This occurs after the acceptor strand invades the donor duplex and creates a displacement loop. The heteroduplex regions represent mismatched base pairing between the two DNA sources, which DNA polymerase extends to complete the repair process.
Q7: How do alleles and phenotypes change through gene conversion in offspring?
Gene conversion alters the distribution of alleles between homologous chromosomes, changing a gene's form or manifestation in offspring. Minor sequence differences between homologous chromosomes don't affect gene function but determine which allele is expressed. For example, a hair color gene's allele determines whether hair is black, blonde, or red, and gene conversion redistributes these allelic variants among offspring.