How the mouse X and Y chromosomes compete with each other to control offspring

October 21, 2019

The molecular function of genes in mice has a major influence on the sex of their offspring, according to a new discovery that reveals more about the impact of genes on animal fertility.

Under normal circumstances, the laws of genetics ensure that sperm carrying an X or a Y chromosome have an equal chance to fertilise the egg, and so parents have an equal chance of having a daughter or a son. However, male mice with partial deletions on their Y chromosome (Yqdel males) break this iron-clad law, producing a distorted sex ratio with many more female than male offspring. Until now, how this occurs has been a mystery.

Now, joint research carried out by teams from the universities of Kent, Cambridge, Essex and Paris Descartes shows that the key lies in the shape of the sperm and how well they are able to swim.

First, the team showed that they could correct the sex ratio distortion by performing IVF fertilisation - proving that the Yqdel males produce equal numbers of X- and Y-bearing sperm and that both types of sperm are equally capable of producing offspring once they actually reach the egg.

Next, the team used high-resolution microscopy and state-of-the-art computer image analysis to show that sperm from Yqdel males are shrunken and distorted. Crucially, the Y-bearing sperm cells were more severely affected than X-bearing sperm cells, suggesting that their function was impaired. To show this, they used FISH labelling ¬- a technique that stains the X or Y chromosomal DNA different colours. This allowed them to identify which cells carried which chromosome, and correlate this to the shape of each individual cell. Using another transgenic strain of mice that "switches off" Y-linked genes rather than deleting them, they proved that the shape difference between X- and Y-bearing sperm was caused by gene expression differences, and not simply by the loss of DNA in the Yqdel males.

Finally, they carried out "sperm races" to isolate the very fastest-swimming sperm cells from Yqdel males, and confirmed via FISH that these tiny athletes were predominantly X-bearing sperm cells - thus explaining the predominance of daughters in Yqdel offspring.

Dr Peter Ellis from Kent's School of Biosciences led the research. He said: 'We have known for some time that the mouse X and Y chromsomes compete to produce female versus male offspring, with genes on the X favouring the production of daughters and genes on the Y favouring sons. Our research now reveals for the first time how this occurs. When the Y-borne genes are deleted, the X-borne genes sabotage sperm head development, making the Y-bearing sperm swim slower and securing a 'selfish' advantage for X-bearing sperm in the race towards the egg. We also found that the use of IVF can reverse this imbalance, which has clear implications for the use of these techniques to influence the sex of mammal offspring.'
Dr Ellis' collaborators were: Benjamin Skinner, Department of Pathology, University of Cambridge, and School of Life Sciences, University of Essex; Claudia Cattoni Rathje, Christina Patinioti and Guiseppe Silvestri, School of Biosciences at the University of Kent; Emma Johnson and Nabeel Affara, University of Cambridge; Deborah Drage of Biomedical Services at the University of Cambridge; and Come Ialy-Radio and Julie Cocquet, Department of Development, Reproduction and Cancer, Paris Descartes University.

The research, 'Differential sperm motility mediates the sex ratio drive shaping mouse sex chromosome evolution' has been published in Current Biology.

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Notes to Editors

The University of Kent is a leading UK university producing world-class research, rated internationally excellent and leading the way in many fields of study. Our 20,000 students are based at campuses and centres in Canterbury, Medway, Athens, Brussels, Paris, Rome and Tonbridge.

With 97% of our research judged to be of international quality in the most recent Research Assessment Framework (REF2014), our students study with some of the most influential thinkers in the world. Universities UK recently named research from the University as one of the UK's 100 Best Breakthroughs of the last century for its significant impact on people's everyday lives.

We are renowned for our inspirational teaching. Awarded a gold rating, the highest, in the UK Government's Teaching Excellence Framework (TEF), we were presented with the Outstanding Support for Students award at the 2018 Times Higher Education (THE) Awards for the second year running.

Our graduates are equipped for a successful future allowing them to compete effectively in the global job market. More than 95% of graduates find a job or study opportunity within six months.

Known as the 'UK's European university', our international outlook is a major focus and we believe in our students developing a global perspective. Many of our courses provide opportunities to study or work abroad; we have partnerships with more than 400 universities worldwide and are the only UK university to have postgraduate centres in Athens, Brussels, Paris and Rome.

The University is a truly international community with over 40% of our academics coming from outside the UK and our students representing over 150 nationalities.

We are a major economic force in south east England, supporting innovation and enterprise. We are worth £0.9 billion to the economy of the south east and support more than 9,400 jobs in the region.

In March 2018, the Government and Health Education England (HEE) announced that the joint bid by the University of Kent and Canterbury Christ Church University for funded places to establish a medical school has been successful. The first intake of undergraduates to the Kent and Medway Medical School will be in September 2020.

We are proud to be part of Canterbury, Medway and the county of Kent and, through collaboration with partners, work to ensure our global ambitions have a positive impact on the region's academic, cultural, social and economic landscape.

University of Kent

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