Sexual revolution in the animal kingdom

Your research focuses on what determines the sex of living organisms. Where does that curiosity come from? 
Wen-Juan Ma: “During my studies, I discovered at some point that sex is not determined in the same way in all living organisms as it is in humans – namely through two different sets of chromosomes. I found that deeply intriguing and wanted to understand why that is the case. Where does this diversity in nature come from? My lab, ‘Evolutionary Genomics of Sex (https://www.wmalab.com)’ combines a wide range of research approaches to find answers to those questions. Sometimes that means field sampling and ecological experiment, but it also includes laboratory cross experiments, working at molecular level, tinkering with specific genes, and comparative and functional genomics.” 

If sex in other species is not determined by X and Y chromosomes, how does it work? 
“In humans, the presence of a single chromosome – the Y chromosome – determines male sex. In birds, it works the other way around: the presence of a different chromosome, the W chromosome, indicates that the individual is female. In many other species, things are even more complex. Sex chromosome turnover is often part of the picture as well. In mammals, that process – where a sex chromosome suddenly appears or disappears – is extremely rare. There are, of course, hormone treatments that can help someone transition in terms of gender, but that is something entirely different. The genetic material itself does not change. In birds, this is also extremely rare. But in amphibians, many fish and reptiles, some insects and flowering plants, sex chromosome turnover happens very frequently.” 

What is the evolutionary advantage of this phenomenon?
“For sex chromosome turnover and sex reversals, we have empirical evidence showing they help sex chromosomes stay forever young, preventing them from degeneration, like in mammals and birds. In a theory proposed by my postdoc mentor Prof. Nicolas Perrin, he called it the ‘fountain of youth’. As you may have heard, the human Y chromosome has become much smaller over evolutionary time, and it could even disappear entirely – albeit only millions of years from now. Over evolutionary time, we gradually lose a piece of genetic information in the Y chromosome. In frogs, this does not happen. There, we see that sex chromosomes remain identical. Genetic material is constantly reshuffled.” 

So they have a kind of self-repair mechanism? 
“That is indeed a good way of putting it.” 

But it clearly does not work perfectly, because degeneration still occurs in those species too?
“Correct. In about 80% of frog species that have been studied, the sex chromosomes are identical in size, but in some lineages that is not the case. And that is precisely what this ERC Grant is for: to find out why degeneration does occur in certain lineages but maintain forever young in most of the others. To do that, we need to analyse enormous amounts of genomic data, so this will keep us busy for quite some time. But that is how we hope to gain insight into these mechanisms.” 

Artificial intelligence is driving spectacular progress in almost every branch of science. Is that also true in your field? 
“Absolutely. A single chromosome can contain hundreds of megabytes of nucleotide information. The university’s IT services sometimes despair at our constant requests for more storage for archive and analyses. At one point, they asked me what our plans were for the coming years, so they could take that into account when investing in server capacity.” 

“AI facilitates us to process all those data and visualize the results much faster than ever before. My students also use AI to help write up or troubleshoot the programming code for applications we need in our research. Sometimes it worries me, for those who do not have any coding background tend to rely on it blindly, while they do not always fully understand what each line of the code means. I advise all my students to use AI tools cautiously and in a responsible way.” 

Earlier you mentioned that some animal and plant species seem to have this self-repair mechanism. Is that where the greatest value of your research lies – could the human species also benefit from it? 
“First of all, I do fundamental research. We need to gain insight into these important questions, regardless of any immediate practical applications. Our work can offer a new perspective on the remarkable diversity of sex chromosome differentiation and sex-determining mechanism across the Tree of Life.” 

“But yes, perhaps our research could one day form the basis of methods to better understand the dynamics of Y chromosome evolution in humans. There is concern that, as a species, we might no longer be able to reproduce if the Y chromosome were to disappear altogether over evolutionary time. I am not entirely convinced of that – nature can be remarkably inventive when it comes to survival – but it is something we need to consider. For instance, new or alternative sex-determining mechanism turned up when the Y chromosome disappeared in the mole voles and Japanese spiny rats. Greater insight into these mechanisms could also help us tackle diseases linked to our sex chromosomes.” 

There is a great deal of public debate about gender-fluid people who decide to change sex, with or without surgery. Are you concerned that your research could be misused in this sensitive discussion? 
“On the contrary. As almost every biologist knows, the absolute opposition between male and female does not exist, except if you look at the world exclusively through the human lens. Nature is infinitely more complex. Just look at the many different ways sex is determined in other species, and intersex or gynandromorph in nature is actually relatively common. Variations on sex as a trait within the human species should therefore not surprise us.” 

Finally, which book or film do you think best connects with your research? And how closely do fiction and reality align? 
“One book I would certainly mention is The Red Queen: Sex and the Evolution of Human Nature by Matt Ridley. Ridley argues that human intelligence and behaviour, such as mate choice, have largely been shaped by sexual selection to pass on genes.” 

“But now that I think about it, I should also mention Jurassic Park, a movie that accidentally touches on some of the questions my lab works on. In the film, dinosaur DNA is reconstructed from mosquito fossils and missing fragments are ‘patched’ with frog DNA (which may sound clever, but actually has no scientific basis whatsoever). The park’s creators hope to control the dinosaur population by making only females. The twist – of course is that reproduction refuses to follow the script. The scientists in the movie discover something that is very true: nature is astonishingly inventive. Or as the main character puts it: “Life will find a way.” As a woman leading a research group in evolutionary genomics – a field where minority voices are still too often underrepresented – I love it when books and films spark curiosity about reproduction, sex determination and evolution. If Jurassic Park gets someone to ask “How does this really work?”, that’s a win – and it’s exactly the kind of question that keeps me excited about science every day.”