All those colorful feathers make it pretty easy to tell a male peacock from a female peahen, and we know that only male lions have manes – well, usually, anyway. But sexual dimorphism is more than just skin-deep. New research has decoded, for the first time, the genetic pathways that lead to sex-linked differences in mammals, including the bits you can’t see.
Beyond the obvious differences in reproductive apparatus, most sexually mature mammals develop some characteristics that diverge between biological males and females. These can range from the more obvious changes in overall body size and coloration, to more subtle differences in the size and composition of internal organs. It’s important to understand these differences because they can affect things like how biological males and females respond differently to medications.
The developmental pathway that an organism follows is determined by its genes. “Until now, however, what was largely unknown was how these programmes differ between female and male individuals and the effects these differences have on the function and cellular composition of organs in adult mammals,” explained first author and doctoral candidate Leticia Rodríguez-Montes in a statement about the new study.
Using RNA sequencing data from five mammalian species (humans, mice, rats, rabbits, and opossums) and one bird (chickens), the authors investigated the sex-based development of the brain, cerebellum, heart, kidneys, and liver. They compared their results across the species and also performed further bioinformatics analysis to look at the protein expression programs that are initiated as these organs develop in the different sexes.
Across all the mammals, a pattern began to emerge. The point at which male and female organs started to take different developmental paths came surprisingly late.
“Almost all of the differences in gene expression abruptly develop only in puberty,” said study co-supervisor Professor Dr Henrik Kaessmann from the Center for Molecular Biology of Heidelberg University. “That means that the genetic programmes responsible for the development of sex-specific organ characteristics are turned on almost exclusively late in the development of the organs, triggered by female or male hormones.”
This was in contrast to the evidence from chickens, which demonstrated that most genes showed a sex bias from the very earliest stages of development. In the mammals, only a small subset of genes were sex-biased throughout development, including the few genes found on the X and Y sex chromosomes.
The level of sex-linked differentiation varied between different organs, but the cell types responsible were the same across all the mammal species. As to why sexual dimorphism could have evolved so rapidly in the first place, the authors speculated that it could be explained by distinct challenges faced by the males and females during speciation.
“In most species we studied, the liver and kidneys exhibit numerous differences in gene expression between the sexes, which in turn lead to marked sex-specific differences in the functionality of these organs,” explained co-supervisor Dr Margarida Cardoso-Moreira of the Francis Crick Institute.
While we may not be able to see them on the surface, these sex differences in internal organs are vital for doctors and scientists to understand; for example, they can help explain why certain diseases of the liver and kidneys are more common in males than females. Calls to address the historical exclusion of women from medical research, and the consequent lack of attention paid to health concerns primarily affecting biological females, have only been increasing in recent years; the more we learn about sexual dimorphism, the more clear it becomes that biomedical science must pay closer attention to sex.
This study shines a light on the deep-rooted genetic mechanisms at work in sexual dimorphism, which is extremely valuable for increasing our understanding of traits that we can see – and those that we can’t – but that have, to date, remained incompletely explained.