The origins of sex chromosomes

What determines whether an animal develops as male or female?

In some species, the answer is written in the genome. In others, environmental cues help guide sex determination. Understanding how these systems evolve may help explain a major evolutionary transition: how sex chromosomes first arise.

Now, researchers at Arizona State University report that Daphnia pulex may offer a rare glimpse into how that transition unfolds in real time. The tiny freshwater crustacean, sometimes called a water flea (but not actually a flea), normally relies on environmental cues to help determine whether offspring become male or female. But the researchers found evidence that some lineages may be shifting toward a more genetically controlled system.

How genetic sex determination evolved from ancestral, environment-based systems has remained a mystery, in part because most species rely exclusively on one or the other, says Michael Lynch, corresponding author of the study.

“The Daphnia system has proved highly useful because the bugs normally have environmental sex determination, with males only being produced in extreme environments," Lynch explains. "We have been fortunate to discover a newly emerging system in which some genotypic isolates are incapable of producing sons under any conditions, whereas other coexisting genotypes produce both male and female offspring.”

Professor Lynch directs the Biodesign Center for Mechanisms of Evolution at ASU and the Biological Integration Institute for Mechanisms of Cellular Evolution. He is also a professor in the School of Life Sciences. He is joined in his research by ASU colleagues, including first author Wen Wei.

The new research has been published in the Proceedings of the National Academy of Sciences.

In mammals, including humans, sex is typically determined by genes through the presence of XX or XY pairs of chromosomes, with Y being the male determinant. In other organisms, however, the environment plays a major role. Some reptiles can develop as either male or female depending on temperature during development. Invertebrates show even more variety, with outside cues such as day length, crowding and other conditions sometimes helping shape sex.

Scientists have long understood that animals can arrive at the same outcome, developing as male or female, by different routes. But the earliest steps in the shift from environmental cues to genetic control have been much harder to observe. The new study suggests that Daphnia pulex may offer a living snapshot of that shift.

The authors describe a Daphnia lineage in which a change to one chromosome created a stretch of DNA tied to sex that is now starting to evolve differently in males and females. That kind of divergence is thought to be one of the early steps in the emergence of sex chromosomes.

The team also identified a gene called "DFH" that appears to play an important role in male development. When researchers reduced or disrupted the gene’s activity in normal male producers, the animals produced far fewer males. Animals with certain mutations in DFH are completely incapable of male production. This suggests that DFH helps steer development toward maleness.

One reason the system is so intriguing is that it does not fit neatly into a single category. In the Daphnia populations studied, some lineages still respond to environmental cues by producing males under the right conditions, while others do not produce males under those same conditions. The authors say this creates a mixed system, with both environmental and genetic influences in play in some individuals but only genetics in others.

The study also points to an unusual parallel with some plants. In those plant populations, some individuals are female-only, while others can function as both male and female. In Daphnia, the pattern is similar: Some lineages produce both sons and daughters, while others produce only daughters. That mix may offer a useful window into how sex chromosomes first arise.

Fully developed sex chromosomes, such as the X and Y chromosomes in mammals, did not appear all at once. They likely took shape gradually through intermediate steps that are difficult to reconstruct long after the fact. This Daphnia lineage may offer one of the clearest views yet of what one of those early steps looks like.

As Professor Lynch puts it, “This now sets the stage for determining the molecular mechanisms that prevent the production of males.”