Crossing over: how are genes shuffled?

A new discovery has explained how proteins help chromosomes shuffle genes – crossing over – during meiosis to make a population more genetically diverse. This could improve our understanding of evolution, fertility and selective breeding.

The study, published in Nature Communications, shows how a protein called HEI10 clumps around spots on the chromosome to trigger homologous recombination – the shuffling of genes – and increase genetic diversity.

Genetic diversity – the variation of genes within a population – makes populations healthier.  On the opposite side, inbreeding removes genetic diversity, which can lead to accumulated diseases and a less robust population.

There are four cornerstones of increasing genetic diversity:

1. Mutations in genes let new genes evolve
2. Random breeding allows new genes to enter a population to avoid inbreeding
3. Random fertilisation allows for a variety of sperm to be selected, which each have different genomes
4. Homologous recombination, or crossing over, where the genes along parent chromosomes are ‘shuffled’ to create a unique genome in the offspring.

The last cornerstone is very important because it means no two siblings are ever exactly the same – they each have their own unique traits and genes (unless they are identical twins).

The crossing over happens during meiosis, a cellular process where a cell divides in two, resulting in an egg or sperm.

During meiosis, the two chromosomes swap a few genes, so the resulting chromosome isn’t exactly the same as the parent or siblings, and each newly crafted chromosome is put into a different cell. These exchanges, or crossovers, are essential for making offspring a little different from their parents, in order to drive evolution.

But this only helps evolution if it is done just right: too much crossing over is stressful to the chromosome, and too little doesn’t create enough diversity.

Despite more than a century of research, however, we previously didn’t know how this was controlled.

Now, a team of researchers, led by Chris Morgan of the John Innes Centre, UK, has used mathematical modelling and 3D simulations to answer the question – a protein called HEI10 was working behind the scenes the whole time.

“Crossover positioning has important implications for evolution, fertility and selective breeding,” says Morgan.

“By understanding the mechanisms that drive crossover positioning we are more likely to be able to uncover methods to modify crossover positioning to improve current plant and animal breeding technologies.”

Using a super-resolution microscope, the team found that the HEI10 proteins clustered along the chromosome, forming a few little groups. When a group got too big, it triggered the crossing-over event.

The team then modelled what would happen depending on the location of the protein groups, or the number of groups present, and confirmed that what they saw under the microscope really was the most efficient form of crossing over.

However, this also means that the process can be modified relatively simply – changing the position or density of HEI10 could allow choice of which genes are shuffled into the resulting cell.

The experiment was done in the model plant Arabidopsis, and could also explain how important crops such as wheat or barley shuffle their genes. The authors hope the research can be extended to mammals in the future.

“This work is a great example of interdisciplinary research, where cutting-edge experiments and mathematical modelling were both needed to unlock the heart of the mechanism,” says co-author Martin Howard, also of the John Innes Centre.

“One exciting future avenue will be to assess whether our model can successfully explain crossover patterning in other diverse organisms.”