I must admit that the technicalities are a bit beyond the mind of this old lady, but the general point is important for fighting the gender agenda. According to a recent scientific paper, there are indeed fundamental differences in biological processes between males and females, from humans right the way down to humble animals: "In female mammals, such as humans and mice, XX females and XY males have different numbers of the X chromosome. To balance this difference, one of the X chromosomes in females is typically silenced. Silencing one X chromosome in females equalizes the gene products on the sex chromosomes. This prevents females from producing double the number of proteins from the X compared to males."
This means that the whole idea of sex being an arbitrary social construction is just false. In fact, it was always absurd, since the mere existence of intersex people with aspects of male and female parts, only made sense if there was a prior conceptualisation of male and female to begin with, or else all is indeterministic. Likewise for the need for sexual realignment surgery which only makes sense if there is a baseline definition of what is a male and what is a female. Clearly, the gender agendas ideology is logically inconsistent, but that does not seem to matter much to political doctrines.
"A new study reveals that platypuses and chickens balance protein levels between sexes through a unique dosage compensation mechanism, different from humans, challenging long-standing genetic assumptions and enhancing our understanding of genetic evolution and regulation.
Researchers at UNSW Sydney have uncovered fundamental differences in biological processes between males and females by examining the unique and diverse sex chromosome systems of the platypus and the chicken.
The findings, published in Proceedings of the National Academy of Sciences (PNAS), are a surprise in the field of genetics. The discoveries will help build a better understanding of how sex chromosomes evolved, how our bodies function—and they could lead to new discoveries in biology.
"Mammals, such as humans, have females with two X chromosomes and males with one X chromosome and one Y chromosome, which creates an imbalance between the sexes," says lead author Dr Nicholas Lister from UNSW's School of Biotechnology and Biomolecular Sciences. "This imbalance is corrected by a process called sex chromosome dosage compensation."
Scientists have long known that animals have solutions to balance sex chromosome differences and achieve 'normal' function.
Dr Lister says: "In female mammals, such as humans and mice, XX females and XY males have different numbers of the X chromosome. To balance this difference, one of the X chromosomes in females is typically silenced. Silencing one X chromosome in females equalizes the gene products on the sex chromosomes. This prevents females from producing double the number of proteins from the X compared to males."
Balancing the scales
Every cell in our bodies uses proteins to perform specific functions.
"They are translated from mRNA, which carry the instructions for cells to make proteins," the study's research lead, Associate Professor Paul Waters, also from UNSW's School of Biotechnology and Biomolecular Sciences, says. "Being male or female affects mRNA levels of X chromosome genes, which we would then expect to affect protein production."
But A/Prof. Waters says this study demonstrates—for the first time—that a balance of proteins occurs between the sexes, even when mRNA levels aren't balanced.
"The findings suggest that dosage compensation is a crucial process in species with differentiated sex chromosomes to ensure that protein levels are balanced," he says. "These results are significant as they suggest that dosage compensation of sex chromosomes is essential after all—and across all vertebrate species, not just placental and marsupial mammals."
Why the platypus and the chicken?The study focused on the platypus and the chicken—two species with vastly different sex chromosome systems that offer valuable insights into the evolution and mechanisms of dosage compensation.
"Platypus are monotreme mammals, with interesting sex chromosome systems," Dr Lister says. "They have five pairs of X chromosomes in females and five Xs and five Ys in males. Birds—such as chickens—have a ZW system, where males have two copies of a Z chromosome and females have a Z and a W chromosome."
A/Prof. Waters says the scientists had already observed near-perfect sex chromosome dosage compensation of RNA between males and females in placental and marsupial mammals.
"However, in birds and monotremes, there is an imbalance of mRNA between the sexes," he says. "This is something we thought was impossible. For the first time, we show that this imbalance is corrected at the protein level. This means that platypus and chicken have a novel mechanism of dosage compensation that is different from how we humans do it."
Are our genes really in control?
Co-author Professor Jenny Graves, from the Department of Environment and Genetics at La Trobe University, had demonstrated that genes on the inactive human X chromosome are not copied into RNA back in 1986.
Silencing at the level of RNA then became the paradigm for all epigenetic silencing.
"As the genes were silenced by their failure to make RNA, the control of dosage compensation was assumed to be at the level of RNA only—not at the level of making proteins," Prof. Graves says.
"But mRNA levels for genes on sex chromosomes weren't balanced in the platypus or the chicken," she says. "So, scientists questioned the assumption that dosage compensation is essential for life."
A/Prof. Waters says that measuring protein levels has been a much trickier endeavor than measuring mRNA levels, due to technological challenges.
"And now that the technology is more sensitive, we can see that the dosage compensation of sex chromosomes between males and females is observed at the protein level in the platypus and the chicken," A/Prof. Waters says. "The males and females of these species make similar amounts of proteins, despite the discrepancies in mRNA quantities."
How will this knowledge be applied?The authors emphasize the complexity of genetic regulation and the importance of considering multiple levels of control in gene expression.
Co-author Dr Shafagh Waters from UNSW's School of Biomedical Sciences says the study paves the way for a deeper understanding of genetic regulation.
"Studying unique species like the platypus provides us with new insights into the cellular and molecular mechanisms that could regulate various aspects of human physiology, or be implicated in disease states," she says. "So, while these processes may not directly apply to human dosage compensation, they illuminate how our bodies manage gene expression and protein production. Our findings have the potential to advance knowledge in evolutionary biology and lead to innovative therapies in medical genetics. Understanding these mechanisms across different species can help identify new targets for diseases where protein dysfunction is key."
Dr Lister says future research will examine the mechanisms that contribute to dosage compensation.
"This work will help us discover other dosage compensation systems in nature," he says. "We can find out how these evolved and how they work in other species."
A/Prof. Waters says, "Understanding these processes in other species can enhance our grasp of gene regulation at a fundamental level."
Reference: "Incomplete transcriptional dosage compensation of chicken and platypus sex chromosomes is balanced by post-transcriptional compensation" by Nicholas C. Lister, Ashley M. Milton, Hardip R. Patel, Shafagh A. Waters, Benjamin J. Hanrahan, Kim L. McIntyre, Alexandra M. Livernois, William B. Horspool, Lee Kian Wee, Alessa R. Ringel, Stefan Mundlos, Michael I. Robson, Linda Shearwin-Whyatt, Frank Grützner, Jennifer A. Marshall Graves, Aurora Ruiz-Herrera and Paul D. Waters, 29 July 2024, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2322360121
In species with differentiated sex chromosomes (XY or ZW), X or Z-borne genes are present in different dosages in male and females. Gene dosage is equalized between sexes by transcriptional silencing of genes on one X in female mammals, so dosage compensation has been thought to be essential. However, imbalanced messenger RNA levels observed between sexes in several species cast doubt on the importance of dosage compensation. Here, we show that although mRNA levels between the sexes in chicken and platypus sex chromosomes were unequal, balance was restored at the protein level. We conclude that dosage compensation is essential in species with differentiated sex chromosomes but that it may be achieved by a combination of transcriptional and post-transcriptional control.
AbstractHeteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between sexes and with autosomes. A need for dosage compensation has long been thought to be critical in vertebrates. However, this was questioned by findings of unequal mRNA abundance measurements in monotreme mammals and birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females and a correlation with differential loading of histone modifications. We also observed unbalanced transcripts of Z genes in chicken. Surprisingly, however, we found that protein abundance ratios were 1:1 between the sexes in both species, indicating a post-transcriptional layer of dosage compensation. We conclude that sex chromosome output is maintained in chicken and platypus (and perhaps many other non therian vertebrates) via a combination of transcriptional and post-transcriptional control, consistent with a critical importance of sex chromosome dosage compensation."