When things get hot, embryonic bearded dragon lizards turn female — and now scientists might know why. New analyses, reported online June 14 in Science Advances, reveal that temperature-induced changes in RNA’s protein-making instructions might set off this sex switch. The findings might also apply to other reptile species whose sex is influenced by temperature.
Unlike most mammals, many species of reptiles and fish don’t have sex chromosomes. Instead, they develop into males at certain temperatures and females at others.
Bearded dragon lizards are an unusual case because chromosome combinations and temperature are known to influence sex determination, says ecologist Clare Holleley of the Commonwealth Scientific and Industrial Research Organisation in Canberra, Australia (SN: 7/25/15, p.7). When eggs are incubated below 32° Celsius, embryonic bearded dragons with two Z chromosomes develop as male, while dragons with a Z and a W chromosome develop as female. But as temperatures creep above 32°, chromosomally male ZZ dragons will reverse course and develop as females instead.
“They have two sex chromosomes, but they also have this temperature override,” Holleley says.
By comparing bearded dragons that are female because of their chromosomes and those that are female because of environmental influences, Holleley and her colleagues hoped to sort out genetic differences that might point to how the lizards make the switch. The team collected RNA from the brain, reproductive organs and other tissues of normal female, normal male and sex-reversed female Australian central bearded dragons (Pogona vitticeps). Then, the researchers compared that RNA, looking for differences in the ways the lizards were turning on genes.
Sex-reversed females turned up the activity of several genes, the researchers found. Two, JARID2 and JMJD3, are part of a family of genes called the Jumonji family, which are known to influence sex differentiation in other animals. For instance, in mammals, a Jumonji gene interacts with SRY, a gene on the Y chromosome that sets off testes development in males. Another is involved in X chromosome inactivation, which ensures that females don’t get a double dose of proteins made by genes housed on their pair of X chromosomes.
The researchers also found changes in the lizard’s RNA. During a cursory skim through the RNA data for JARID2 and JMJD3, study coauthor Ira Deveson noticed something strange. RNA carries information from DNA that gets translated in proteins, and normally it gets edited before translation — certain sections get taken out. But in sex-reversed females, one of the sections normally removed remained.
The observation “was kind of fortuitous,” says Deveson, a biologist at the Garvan Institute of Medical Research in Sydney.
Through closer investigation, he found that the RNA sections that stuck around contained chemical codes that act as stop signs, prematurely halting the translation of the RNA from these two genes into proteins.
It’s not clear whether the different RNA means a protein doesn’t get made at all in dragons incubated at high temperatures or whether the proteins made are modified, smaller versions of their usual selves. That’s a target for future research, says Holleley.
Either way, previous studies have shown that proteins made from Jumonji genes work to control many other genes that orchestrate developmental processes — and that environmental stress, such as from heat, can change the way these genes turn on and off.
Heat messes with the proteins made from JARID2 and JMJD3, which in turn mess with the proteins made by other sex-related genes, the researchers propose. Sex in bearded dragons is determined by amounts of certain proteins — males, with two Z chromosomes, typically get a double dose of anything coded on the Z chromosome. So such a disruption could flip the sex from male to female.
“The data are tantalizing,” says Turk Rhen, a biologist at the University of North Dakota in Grand Forks who wasn’t part of the study. But, he says, the researchers looked at RNA from only adult bearded dragons. Studying embryonic dragons is important for piecing together gene activity during sex determination.
Holleley and Deveson did find similar effects in embryonic sex-reversed embryonic alligators and turtles. That suggests that RNA editing differences might start early in development, and might extend to other reptiles who use temperature (hot or cold) as a sex-determining cue. In the future, the team hopes to investigate embryonic dragons as well, snipping out the JARID2 and JMJD3 genes from their DNA and tracking what happens as the dragons develop.