Welcome back to Science You Can Bring Home To Mom! This month, in honor of pride month, we are discussing the science behind gender and biological sex. Just like many other attributes of the human brain, our common understanding of gender is rife with oversimplification and misunderstanding. But digging a little deeper can help us learn to empathize with others and understand ourselves better. As a human attribute, gender is inherently biopsychosocial—it’s influenced by biological, psychological, and social factors. And each of these paradigms is far more complex than it may seem on the surface. Next week, we’ll dissect some of the complicated psychological and social factors that underlie each person’s unique sense of gender. But for now, I want to talk about the biological factors influencing gender, namely biological sex. It’s a common mistake to confuse biological sex for gender and vice versa, but this makes about as much sense as attributing a person’s sense of humor to their genetic code. Even if you ignore the psychological and social factors involved, the biology of the human body is far too complex to attribute issues of human identity to a single gene or biological marker. As we’ll see, there are many different ways to categorize biological sex, but these classifications are not practical for dividing up real people.
One of the problems with referring to a person in terms of their biological sex is often we have an ambiguous definition of what that actually means. There are really three different classification systems we mean when we refer to someone’s biological sex: genetic, hormonal, and neurobiological. But what we’ll see is these systems are actually much more complex than they appear to be on the surface. There are certainly aggregate differences between the sexes—for humans and many animals—but those differences are often completely outstripped by the diversity of individuals within groups. There are very few archetypes in biology—life is defined by diversity and individuality. What this means is that the strict biological binaries we’ve used to simplify our classification of people are not really representative of reality. When we start looking deeper, we find that most “binary” traits actually fall into much more continuous spectrums (similar to normal distributions for height below).
In humans and many other animals, biological sex determination starts with the sex chromosomes. Eggs and sperm are the only cells in the body that are haploid, meaning they have only one set of chromosomes (23 for humans). These cells are haploid so that when they fuse together, they create a diploid embryo with two of each chromosome (46). These chromosome pairs are homologous—they have different copies of the same genes—so the embryo’s inheritance of different traits is impacted by what combination of genes they end up with from each parent. The only set of chromosomes that isn’t necessarily homologous are the sex chromosomes. Sex chromosomes in an embryo can be XX or XY, depending on the sex chromosome donated by the sperm. The Y chromosome is much smaller than the X chromosome and contains fewer genes (in fact, there is evidence that the Y chromosome is slowly shrinking over generations). But the genes that the Y chromosome does contain are primarily responsible for sex determination. In particular, the Sex-determining Region Y gene (SRY) codes for the testis-determining factor (TDF) protein that kicks off male development in utero.
Most of the other sex chromosome genes are found on the X chromosome. The traits that come from genes on the X chromosome are called sex-linked traits because they are expressed differently in males versus females. We talked about this kind of inheritance in our post on muscular dystrophy from last year. The gene for muscular dystrophy is recessive, so as long as you have one functional copy of the gene, you won’t have the disorder. But males have only one X chromosome, so if they inherit one muscular dystrophy gene, they will have muscular dystrophy. For this reason, sex-linked recessive disorders tend to be much more common in males compared to females, while females are more likely to be silent carriers of the faulty gene. In addition to muscular dystrophy, hemophilia and red-green color blindness are sex-linked disorders. In cats, fur color is a sex-linked trait, which results in another interesting phenomenon—calico cats. Females have significantly more copies of X-linked genes than males because of their double X status, resulting in over-dosing of those genes. To combat this, in the early stages of development, one of the X chromosomes is shut off. X-chromosome inactivation is random, and it happens late enough in embryonic development that it results in a patchwork of activated sex-linked genes. For cats, this phenomenon can present as the patchwork fur color associated with calico cats—which pretty much only occurs in females. X-inactivation happens in humans too, although it isn’t as visible.
Occasionally, there are calico cats who are male. But how does that happen, if calico fur is caused by differential inactivation of two different X chromosomes? These cats likely have Klinefelter syndrome where they have XXY sex chromosomes. Klinefelter syndrome and other sex chromosome abnormalities occur when there is an error in the division of sex chromosomes into egg or sperm cells. Sex chromosome abnormalities are less likely to be lethal than abnormalities in other chromosomes, and often, they are not even diagnosed. In humans, people with Klinefelter syndrome present as male (due to the presence of the SRY gene in the Y chromosome) but have lower levels of testosterone than XY males. Another sex chromosome abnormality, Triple X syndrome, results in female-presenting people with XXX sex chromosomes. People with Triple X may be slightly taller and may have problems with infertility, but they often have no physical indications of the abnormality. In any chromosomal abnormality, X-chromosome inactivation compensates to ensure only one X chromosome is expressed for any given cell.
There is also a subset of XX people who are male-presenting from birth and a subset of XY people who are female-presenting from birth due to accidental movement or deletion of the SRY gene. It’s impossible to reliably predict the underlying genetics of a person based on their sex presentation at birth, and very few people get genetic testing for this purpose. In fact, there is some controversy over whether sex chromosome abnormalities should be included in the definition of “intersex”—a catchall term for people whose biological sex cannot be easily classified at birth, usually because of ambiguous genitals. Oftentimes, the expression of these sex chromosome abnormalities isn’t visibly apparent because of the unique interplay of genetics, hormones, and environment.
Beyond the complexity of genetic sex determination, the actual expression of genetic factors related to biological sex relies on the constantly changing and often unpredictable interaction of hormones. Hormones are long-term chemical messengers that circulate throughout the body and coordinate a variety of biological processes. The hormones involved in sex determination and reproduction are estrogen, progesterone, and testosterone. Everyone has some amount of each of these hormones. The relative levels of each sex hormone, the changes in those levels, and the localization of sex hormone activity can all influence sex determination and reproduction. These levels change throughout our lives as part of our normal development and in response to environmental factors.
In terms of sex determination, the development of structures associated with biological sex is primarily driven by hormone levels. Around six weeks into development, the presence of SRY and other genes associated with the Y chromosome stimulates the formation of testes and floods the developing fetus with testosterone, which promotes the development of male reproductive organs. On the other hand, the absence of SRY and the presence of X-chromosome sex-determining genes, like WNT4 and RSPO1, stimulate the formation of ovaries and the production of estrogen, which promotes the development of female reproductive organs. Of course, this process isn’t linear, and there are plenty of genetic and environmental factors that can interrupt “normal” sex development. For example, a subset of XY individuals has Androgen Insensitivity Syndrome (AIS) where the developing fetus doesn’t respond to the surrounding testosterone resulting in female or ambiguous reproductive development.
So clearly, there is a lot going on when it comes to sex determination, and there’s a lot of room for ambiguity and nuance in this process. We know very little about how the interplay of genetics, hormones, and environment impact early physical, neurological, and psychological development. The prevailing scientific thought of the 20th century was that there must be some innate difference between the sexes on a neurobiological level. But no such definitive difference has ever been found. In reality, the neurobiological differences between males and females aren’t nearly as distinct as the differences between the individuals within these groups. The traits we come to associate with males or females are more likely the result of social factors during early childhood development that follow us throughout our lifetime. For more information about the neurobiology and psychology of sex and gender, check out this video lecture with Gina Rippon:
Next week, we’ll dive deeper into the social and psychological aspects that make up gender. For now, check out last month’s series on mental health. Comment on this post or email me at contact@anyonecanscience.com to let me know what you think about this week’s blog post and tell me what sorts of topics you want me to cover in the future. And subscribe below for weekly science posts sent straight to your email!
