Quick look
A new study led by an Iowa State University evolutionary biologist suggests an antenna-like cellular sensor that’s a growing focus in human health could play a central role in how turtles become male or female, which in most species is based on incubation temperature.
AMES, Iowa – When most baby turtles hatch, their sex depends on the temperature of the sand or soil where their mother laid her eggs. Warm incubation brings females, while cool nests produce males.
Based on a new study led by an Iowa State University evolutionary biologist, a once-ignored cell component – primary cilia, an antenna-like protrusion from most types of animal cells – may help turtle embryos detect that sex-deciding warmth. It’s the first time that turtle sex determination has been linked to primary cilia, but the cellular sensor is a growing focus of human health research, as they are now recognized as important for development and disease. That heightens the interest from Nicole Valenzuela’s research team.
“We have concluded we need to open a whole new research avenue to characterize primary cilia in turtles and see how they’re composed, what they are doing, and how they are changing and responding to temperature and other cell signals. It’s basic science that’s also biomedical science,” said Valenzuela, professor of ecology, evolution and organismal biology at Iowa State.
A surprising analysis
Valenzuela studies how evolution and environmental factors influence complex traits such as sex determination, with a particular focus on turtles. Over more than 200 million years, an especially long lineage for a four-limb vertebrate, some species of turtles have developed sex-specific chromosomes that dictate whether they become male or female, but most are still temperature-dependent.
Looking to better understand the basis of that change, Valenzuela’s team identified what genes are involved in making the reproductive organs of two species that determine sex in different ways: painted turtles that have retained the ancestral temperature-driven method and spiny softshell turtles, which have sex chromosomes.
Researchers then integrated data on gene expression, protein-protein interactions and protein-DNA interactions to model molecular regulatory networks for the sex-development genes – essentially, a snapshot of their cellular control circuitry as gonads are emerging. Comparing the regulatory networks showed painted and spiny softshell turtles share 89 transcription factor hubs, special proteins that turn clusters of genes on and off.
Of the 89 shared hubs, 50 were unchanged between species, perhaps representing the underlying core of building turtle gonads, Valenzuela said. But looking at the hubs that changed the most and cross-referencing them against databases that track known gene functions, researchers kept seeing a term they didn’t anticipate or know well: primary cilia.
“We said, ‘What’s going on here,'” Valenzuela said.
A promising direction
Other scientists in her field had a similar reaction. When Valenzuela presented the study at the International Symposium on the Biology of Vertebrate Sex Determination earlier this year, she asked a roomful of colleagues who had heard of primary cilia. Only a couple of hands went up.
Though unexpected, the relationship between primary cilia and sex differentiation in turtles appears robust. Multiple approaches to analyzing their regulatory network models linked transcription factor hubs to primary cilia, with some gene targets shifting from the antenna’s function in painted turtles to its structure and formation in spiny softshells. And a forthcoming study from Valenzuela’s lab that looked at turtle embryo histones – proteins that give DNA a spool to wind around – uncovered some related associations, she said.
“All of a sudden, we’re finding all these different lines of evidence pointing in the same direction,” she said.
Once the researchers began delving into recent research into primary cilia, the potential connection began to make more sense. Primary cilia detect environmental cues outside of cells, including temperature changes, and manage major signaling pathways, some of which have been connected to mammalian sexual development.
While further research is needed to validate the researchers’ hypothesis that the cellular antenna plays a direct role in turtle sex determination, anything learned about primary cilia could inform ongoing research into their role in human well-being, Valenzuela said. Dysfunctional cilia have been implicated in an expanding list of human disorders that includes cancer as well as brain and lung diseases.
And if primary cilia have a broad role sensing temperature in turtles, it could shed more light on the molecular mechanics of some turtles’ remarkable ability to withstand extreme cold, which would be a valuable trait to harness for human health care as well, Valenzuela said.
“Turtles happen to be very interesting from a thermal sensory perspective,” she said.
