Biology

Evidence for a Novel Genetic Recombination Theory

Evidence for a Novel Genetic Recombination Theory

Genetic recombination is the exchange of genetic material between organisms that results in the production of offspring with traits that differ from those found in either parent. Genetic recombination during meiosis in eukaryotes can result in a novel set of genetic information that can be passed down from parents to offspring.

Every cell in most higher organisms, including humans, contains two copies of each gene, known as alleles. Each parent passes on one allele to each of their children. Adjacent genes are usually inherited together because they are linked together on chromosomes. This, however, is not always the case. Why?

The answer is recombination, which occurs during cell division and shuffles the allele content between homologous chromosomes. Crossovers occur when homologous chromosomes come into contact with each other, resulting in the exchange of genetic material.

These results are an exciting insight into a process that has baffled scientists for over a hundred years. Next, we want to better understand what controls the dynamics of the HEI10 droplets and how they promote crossovers. If we can get a better handle on how the process works, this may allow us selectively boost recombination during plant breeding, enabling the assembly of combinations of beneficial alleles that have remained out of reach.

David Zwicker

Crossovers have long piqued the interest of scientists, particularly plant breeders, because manipulating the crossover process has the potential to increase genetic diversity and assemble desired allele combinations that boost crop productivity. Crossovers are subject to the “Goldilocks principle,” which states that at least one crossover is required per chromosome pair for successful sexual reproduction; in fact, a lack of crossovers is a major cause of human trisomy, such as Down Syndrome.

Crossover numbers are also strictly regulated and rarely exceed three. Crossover interference, a phenomenon in which crossovers inhibit additional crossovers in their vicinity, achieves this limit on crossover number and thus recombination. However, the mechanism of this interference has remained a mystery since it was first described 120 years ago.

New model of crossover interference

Now, a team led by Raphael Mercier at the Max Planck Institute for Plant Breeding Research in Cologne, Germany, have found convincing evidence in support of a recently proposed model of crossover interference.

Mercier and his team, together with collaborators, in work spearheaded by Stéphanie Durand, Qichao Lian, and Juli Jing, achieved these insights by manipulating the expression of proteins known to be involved in either promoting crossovers or in connecting chromosomes together in the model plant Arabidopsis thaliana, a species which Mercier and his colleagues use to gain fundamental insights into the mechanisms of heredity.

Evidence-for-a-Novel-Genetic-Recombination-Theory-1
Evidence for new theory of genetic recombination

Boosting expression of the pro-crossover protein HEI10 resulted in a significant increase in crossovers, as did disrupting the expression of the protein ZYP1, a constituent of the synaptonemal complex, a protein structure that forms between homologous chromosomes.

When the scientists combined the two interventions, they were surprised to observe a massive increase in crossovers, showing that HE10 dosage and ZYP1 jointly control CO patterning. Importantly, massively increasing crossovers in this way barely affected cell division.

The considerable increase in crossovers upon increasing HEI10 levels chimes well with an emerging model for how crossover number is regulated. This model, formulated by David Zwicker and his team at the Max Planck Institute for Dynamics and Self-Organization in Göttingen, Germany, is based on diffusion of the HEI10 protein along the synaptonemal complex and a coarsening process leading to well-spaced HEI10 foci that promote crossovers.

In the model, HEI10 initially forms multiple small foci and is progressively consolidated into a small number of large foci that co-localize with sites of crossovers. In this simple model, increasing the levels of HEI10 will result in more foci and therefore more crossovers; thus, the formation of droplets along an axis appears to be the determinant of crossover sites.

Mercier is excited by the team’s findings but is also already looking ahead: “These results are an exciting insight into a process that has baffled scientists for over a hundred years. Next, we want to better understand what controls the dynamics of the HEI10 droplets and how they promote crossovers. If we can get a better handle on how the process works, this may allow us selectively boost recombination during plant breeding, enabling the assembly of combinations of beneficial alleles that have remained out of reach.”

In eukaryotes, recombination can also occur during mitosis, where it usually involves the two sister chromosomes formed after chromosomal replication. Because the sister chromosomes are usually identical, new allele combinations are not produced in this case. Recombination occurs between similar DNA molecules during meiosis and mitosis (homologous sequences). Non-sister homologous chromosomes pair with each other during meiosis, resulting in recombination between non-sister homologues. Recombination between homologous chromosomes is a common mechanism used in DNA repair in both meiotic and mitotic cells.