How Chromosomes Find Their Partners

The body cells of humans and animals contain a double set of chromosomes. One half of the genetic material comes from the mother, the other stems from the father.

During the formation of sperm or egg cells, this double set of chromosomes must be halved to form a single set. This takes place during what is known as meiosis. In this process, a cell with a double set of chromosomes gives rise to daughter cells with a single set of chromosomes. This halving is necessary because, during fertilisation, two germ cells - and thus their genetic material - fuse together. Afterwards, there is once again a double set of chromosomes. If this did not happen, the number of chromosomes would double from one generation to the next as the germ cells fuse.

In order to ensure that chromosomes can be distributed evenly during meiosis, the maternal and paternal versions of the same chromosome must locate one another within a cell and temporarily pair up. This is no easy task amidst the vast jumble of the cell nucleus. Mismatches must be avoided at all costs during the pairing phase to avoid chromosomes being distributed incorrectly.

But how do the matching chromosome pairs actually find each other? ETH researchers led by Madhav Jagannathan, a professor at the Department of Biochemistry, and his PhD student Lena Skrutl have now investigated - using the example of egg cell formation in female fruit flies (Drosophila) - how this 'matchmaking' process takes place in the cell nucleus - and have made a surprising discovery.

No longer genetic 'rubbish'

For a long time, scientists have known that large swathes of animal genomes are comprised of repetitive DNA sequences. Known as satellite DNA, experts regarded these repeats as useless 'junk DNA' because they do not contain blueprints for proteins. Nor were other researchers able to attribute any role to satellite DNA during meiosis. Indeed, when they removed these satellite DNA repeats from just one chromosome, chromosome pairing still proceeded without error.

Now, in the journal external page Nature Communications , the researchers from ETH have demonstrated that unique satellite DNA patterns on each pair of chromosomes, comparable to a barcode on a product in a supermarket, help matching chromosomes find each other.

Junk DNA becomes a matchmaker

The ETH researchers led by Prof. Jagannathan argue that it is not enough to simply remove satellite DNA from just one chromosome. With only one 'barcode' disrupted, all of the other chromosome pairs with intact satellite DNA 'barcodes' can find each other. Ultimately, only the pair of chromosomes from which the researchers removed the barcode remains. They find each other like the last two face-down cards in a game of Memory.

Therefore, the ETH researchers removed the satellite DNA barcode from two different chromosomes, leaving the two pairs without any guidance.

And indeed: without their barcode, the partner selection went awry and failed, meaning that the chromosomes frequently docked with the wrong partners. "This showed us that satellite DNA functions as a recognition aid and ensures that the chromosomes that belong together can reliably find one another," says Lena Skrutl, the study's lead author.

A glue-like protein binds matching chromosomes

Simply recognising each other, however, is not enough. The researchers went on to discover that chromosome pairing also requires a molecular 'glue' to properly 'marry' the two partners together. A protein called D1 plays this role. It recognises the matching barcodes on the chromosomes that belong together, binds them and adheres to the two together.

However, if the recognition pattern on one of the two chromosomes is altered - for example, if part of the barcode is deleted or changes occur due to natural mutations - the D1 protein can bond two chromosomes together that do not belong together. The pairing then goes wrong.

"Our research answers the question of how chromosome pairs recognise each other in the fruit fly Drosophila, so that meiosis proceeds correctly," ETH Professor Jagannathan states. Whether this mechanism is universal and, for example, also plays a role in humans has not yet been investigated.

"While we have carried out pure basic research on the model organism Drosophila, we believe it is possible that this pairing mechanism also occurs in other species." One thing, however, has already become clear to Jagannathan: "The term 'junk DNA' is no longer tenable. We clearly demonstrate that this so-called rubbish has an important function during meiosis in the fruit fly," he emphasises.

Possible role in speciation

The new findings also explain how new species arise. Satellite DNA changes a great deal more rapidly than the rest of the genome. As long as individuals of a species produce offspring with one another, the satellite DNA barcodes remain similar across the population due to the constant mixing of genetic material.

Individuals with recognition patterns that differ too greatly suffer from meiosis defects and are unable to reproduce.

However, if a population of an animal species becomes geographically isolated - for example, due to the formation of a mountain range over millions of years - the satellite DNA in both groups evolves independently of one another. When the two groups meet again after a long period of time, the recognition patterns of the chromosomes no longer match. The result: the animals can no longer reproduce, and one species has become two.

'Studies on crosses between Drosophila melanogaster and its relative Drosophila simulans are consistent with this idea,' says Jagannathan. The two species diverged two to three million years ago. The barcodes of their chromosomes now differ so greatly that massive chromosome pairing defects occur during meiosis in hybrids.