Biology Blurs Line Between Sexes and Behaviors

Summary: Researchers have identified a genetic switch in neurons that can toggle between sex-specific states when necessary.

Source: University of Rochester

Biological sex is typically understood in binary terms: male and female. However, there are many examples of animals that are able to modify sex-typical biological and behavioral features and even change sex. A new study, which appears in the journal Current Biology, identifies a genetic switch in brain cells that can toggle between sex-specific states when necessary, findings that question the idea of sex as a fixed property.

The research– led by Douglas Portman, Ph.D., an associate professor in the University of Rochester Department of Biomedical Genetics and the Del Monte Institute for Neuroscience -was conducted in C. elegans, a microscopic roundworm that has been used in labs for decades to understand the nervous system. Many of the discoveries made using C. elegans apply throughout the animal kingdom and this research has led to a broader understanding of human biology. C. elegans is the only animal whose nervous system has been completely mapped, providing a wiring diagram – or connectome – that is helping researchers understand how brain circuits integrate information, make decisions, and control behavior.

There are two sexes of C. elegans, males and hermaphrodites. Though the hermaphrodites are able to self-fertilize, they are also mating partners for males, and are considered to be modified females. A single gene, TRA-1, determines the sex of these roundworms. If a developing worm has two X chromosomes, this gene is activated and the worm will develop into a female. If there is only one X chromosome, TRA-1 is inactivated, causing the worm to become a male.

The new study shows that the TRA-1 gene doesn’t go completely silent in males, as had been previously thought. Instead, it can go into action when circumstances compel males to act more like females. Typically, C. elegans males prefer searching for mates over eating, in part because they can’t smell food as well as females do. But if a male goes too long without eating, it will dial up its ability to detect food and acts more like a female. The new research shows that TRA-1 is necessary for this switch, and without it hungry males can’t enhance their sense of smell and stay locked in the default, food-insensitive mate-searching mode. TRA-1 does the same job in juvenile males – it activates efficient food detection in males that are too young to search for mates.

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TRA-1 does the same job in juvenile males – it activates efficient food detection in males that are too young to search for mates. Image is in the public domain.

“These findings indicate that, at the molecular level, sex isn’t binary or static, but rather dynamic and flexible,” said Portman. “The new results suggest that aspects of the male nervous system might transiently take on a female ‘state,’ allowing male behavior to be flexible according to internal and external conditions.”

A separate study appearing Current Biology by a team of collaborating researchers at Columbia University further describes the complex molecular mechanism by which TRA-1 is controlled by sex chromosomes and other cues.

Additional co-authors of the study include Hannah Lawson, Leigh Wexler, and Hayley Wnuk with the University of Rochester.

Funding: The research was supported with funding from the National Institute of General Medical Sciences.

About this individual differences research article

University of Rochester
Mark Michaud – University of Rochester
Image Source:
The image is in the public domain.

Original Research: Open access
“Dynamic, Non-binary Specification of Sexual State in the C. elegans Nervous System” by Douglas Portman, et al. Current Biology.


Dynamic, Non-binary Specification of Sexual State in the C. elegans Nervous System

• The master hermaphrodite sexual regulator tra-1 is expressed in male neurons
• tra-1 acts in juvenile males to suppress an adult-specific sexual dimorphism
• In adult males, tra-1 is necessary for the suppression of dimorphism by starvation
• Genetic control of sexual state in the nervous system is neither binary nor static

Biological sex in animals is often considered a fixed, individual-level characteristic. However, not all sex-specific features are static: for example, C. elegans males (XO) can sometimes exhibit hermaphrodite (XX)-like feeding behavior. (C. elegans hermaphrodites are somatic females that transiently produce self-sperm.) Essentially all somatic sex differences in C. elegans are governed by the master regulator tra-1, whose activity is controlled by chromosomal sex and is necessary and sufficient to specify the hermaphrodite state. One aspect of this state is high expression of the chemoreceptor odr-10. In hermaphrodites, high odr-10 expression promotes feeding, but in males, low odr-10 expression facilitates exploration. However, males suppress this sex difference in two contexts: juvenile males exhibit high odr-10 expression and food deprivation activates odr-10 in adult males. Remarkably, we find that both of these phenomena require tra-1. In juvenile (L3) males, tra-1 is expressed in numerous neurons; this expression diminishes as individuals mature into adulthood, a process that requires conserved regulators of sexual maturation. tra-1 remains expressed in a small number of neurons in adult males, where it likely has a permissive role in odr-10 activation. Thus, the neuronal functions of tra-1 are not limited to hermaphrodites; rather, tra-1 also acts in the male nervous system to transiently suppress a sexual dimorphism, developmentally and in response to nutritional stress. Our results show that the molecular and functional representation of sexual state in C. elegans is neither static nor homogeneous, challenging traditional notions about the nature of biological sex.

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