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An important meiotic quality control mechanism is not conserved in birds

09 March 2012

Research published by NIMR scientists has traced the evolution of a mechanism thought to be important in the elimination of germ cells with defective chromosome pairing. The work is published in PLoS Genetics.

Meiosis is the essential step of germ cell maturation in which the chromosome number is halved. In preparation for the first cell division the homologous chromosomes undergo pairing and exchange of genetic information through recombination. Errors in chromosome pairing can lead to the generation of gametes and embryos with the wrong chromosome number, a condition known as aneuploidy. It is therefore important that germ cells exhibiting these errors are eliminated.

Previously, James Turner (pictured) and Paul Burgoyne have shown that when chromosomes fail to pair, they are transcriptionally inactivated. This process, called meiotic silencing, starves germ cells of essential gene products and in doing so may lead to their demise. By weeding out such defective germ cells, meiotic silencing has been proposed to represent a mechanism that safeguards against aneuploidy. It is currently unclear whether meiotic silencing is an ancient mechanism conserved in all vertebrates or whether it arose recently during mammalian evolution.

To resolve this question, Silvana Guioli, Robin Lovell-Badge (pictured) and James Turner, from NIMR’s Division of Stem Cell Biology and Developmental Genetics, have investigated whether meiotic silencing occurs in birds, which diverged from mammals around 300 million years ago. Previous studies had concluded that in these organisms all homologous chromosomes engage in full pairing during meiosis. However, the researchers found that the sex chromosome pair, termed the "Z" and "W" chromosomes, exhibit an intrinsic fragility that often resulted in them never pairing with one another. This aberrant ZW pair would be an ideal target for a meiotic silencing response if this process were to operate in chickens.

By analysing nascent RNA expression for different genes on the Z chromosome in individual germ cells, the researchers were surprised to find that meiotic silencing does not occur in this organism. This suggests either that meiotic silencing evolved only in mammals, or that it arose earlier in evolution but was subsequently lost in the avian lineage. Importantly, the researchers also found that germ cells with defective ZW pairing progressed normally through meiosis without being eliminated.

Our findings show that in an organism without meiotic silencing, germ cells with unpaired chromosomes are not eliminated. This is exciting because it provides support for the theory that meiotic silencing does indeed act as a control mechanism to eliminate germ cells with defective chromosome pairing. Our work also indicates that meiotic silencing could be a relatively recent evolutionary invention, being largely or completely restricted to mammals. The reasons for this are unclear and will require us to establish whether meiotic silencing also occurs in other, more distantly related vertebrates

Chicken oocyte containing a ZW pair that failed to synapse and recombine

Click image to view at full-size

Z and W, identified using chromosome paint (green and red respectively) are schematised on the right. Green lines represent a component of the protein complex forming along the chromosomes. Thick lines are synaptic pairs; thin lines asynaptic chromosomes; only Z and W are asynapsed. The red foci are sites of crossover. No evidence of DNA exchange is present on the ZW pair. Z and W asynapsed chromosomes retain unrepaired DNA breaks (blue foci) that will be carried over to the next stage.