New findings suggest an explanation for how chromosomal recombination is regulated during sexual reproduction
In most higher organisms, including humans, each cell carries two versions of each gene, called alleles. Each parent passes on an allele to each offspring. Since they are linked to each other on the chromosomes, adjacent genes are usually inherited together. However, this is not always the case. Why?
The answer is recombination, a process that mixes allelic content between homologous chromosomes during cell division. Mechanically, recombination is achieved through crossovers, where homologous chromosomes come into contact, resulting in the exchange of genetic material.
Crossbreeding has long fascinated scientists and especially plant breeders, because manipulating the breeding process offers the potential to increase genetic diversity and assemble desired combinations of alleles that boost crop productivity. The crosses are subject to a “Goldilocks principle”; at least one is required per pair of chromosomes for successful sexual reproduction; indeed, a lack of crossover is a major cause of human trisomy as in the case of Down syndrome. The number of crossings is also strictly regulated and usually does not exceed three. This limit on the number of crossovers, and therefore on recombination, is achieved by crossover interference, a phenomenon by which crossovers inhibit additional crossovers in their vicinity. However, how this interference works has remained a mystery since it was first described around 120 years ago.
New cross-interference model
Now, a team led by Raphael Mercier at the Max Planck Institute for Plant Breeding Research in Cologne, Germany, has found compelling evidence to support a recently proposed model of cross-interference. Mercier and his team, in collaboration with collaborators, in work led by Stéphanie Durand, Qichao Lian and Juli Jing, obtained this information by manipulating the expression of proteins known to be involved either in promoting crossbreeding or in the connection of chromosomes in the model plant. Arabidopsis thaliana, a species that Mercier and his colleagues are using to gain fundamental insights into the mechanisms of heredity. Stimulating expression of the pro-crossover protein HEI10 resulted in a significant increase in crossover, as did disruption of 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 see a massive increase in crossover, showing that the HE10 and ZYP1 dosage jointly control CO patterning. Importantly, the massive increase in crossover in this way barely affected cell division.
The dramatic increase in crossover with increasing HEI10 levels fits well with an emerging pattern of how the number of crossovers 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 the diffusion of the HEI10 protein along the synaptonemal complex and a magnification process leading to well-spaced HEI10 foci that promote crossbreeding. In the model, HEI10 initially forms several small foci and is gradually consolidated into a small number of large foci that co-locate with crossover sites. In this simple model, increasing levels of HEI10 will result in more outbreaks and therefore more crossovers; thus, the formation of droplets along an axis appears to be the determinant of crossover sites.
Mercier is excited about the team’s findings but is already looking to the future: “These results are an exciting insight into a process that has puzzled scientists for over a hundred years. Next, we want to better understand what controls the dynamics of HEI10 droplets and how they promote crossings. If we can better understand how the process works, it may allow us to selectively stimulate recombination during plant breeding, allowing the assembly of beneficial allele combinations that have remained out of reach.