A Scientific Defense of the Human Gender Spectrum

11 min readAug 6, 2023

Last Updated August 6, 2023.

This article accumulates scientific arguments that advocate for the principle of human gender as a spectrum, rather than a binary system.

With the expanding influence of social media, anti-LGBTQ+ sentiment festers within certain factions of the internet. More specifically, increased vitriol towards transsexual people is visible online. There exist general misunderstandings of the fundamental scientific principles that concern the LGBTQ+ community. This article is meant to refute as many of those points as possible. [1]

Stating what should be the obvious, it’s important to note that being LGBTQ+ is not a pathology or a condition that needs an ‘explanation’. It’s part of the normal spectrum of human identity. While there’s an interest in understanding the biology of gender identity from a scientific perspective, the existence of LGBTQ+ people doesn’t need to be ‘justified’ by an evolutionary advantage. The key focus should be on ensuring the rights, dignity, and well-being of transgender individuals in society.

That being said, this article discusses why gender is not as simple as the common myth that “XX sex chromosomes must always equal the female gender, and XY sex chromosomes must always equal the male gender”.

The numbers in brackets ([]) demarcate when a citation occurs, and can be traced to the “Citations” section at the end of this article.

Section I - Conditions & Gender

I.1. Sex Chromosomes & Gender:

While this section addresses “conditions” and “syndromes” as it relates to transsexual people, it is important to note that this is not the only defense of LGBTQ+ people within this article. Therefore, don’t come to the conclusion that: “if these ‘conditions’ are eradicated, then the topic of transsexual people would cease to exist” - later in the article, it is clarified why this topic is important. Further on, different defenses are explained.

People’s experience of gender identity is individual and subjective. The following conditions often influence physical development, sometimes in ways that blur traditional sex-based categories. It’s important to note that they don’t predetermine one’s gender identity. [2] [3]

That being said, what follows is a list of a few conditions that are caused by alterations in the sex chromosomes. Each condition has a biological sex at birth that is attached to it. However, the symptoms of the conditions often clash with the biological sex assigned at birth. Therefore, it is not beyond comprehension why people with these conditions may seek to transition away from their biological sex, and find another place on the gender spectrum.

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I.1.A. Klinefelter Syndrome (47 XXY): When a male has one extra X chromosome. [4]

Relevant Symptoms Include: Weaker than average muscles, dyspraxia, less than average body hair, gynecomastia, testicular atrophy (and poor testicle function), low libido, and infertility. [4] [5]

**Klinefelter Syndrome Karyotype.** Photo Credit: Sachin Nuguru.

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I.1.B. Turner Syndrome (45 X): When a female is missing one X chromosome. [6]

Relevant Symptoms Include: Amenorrhea, mammary hypoplasia, infertility. [7] [8]

**Turner Syndrome Karyotype.** Photo Credit: Sachin Nuguru

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I.1.C. Triple X Syndrome (47 XXX): When a female has one extra X chromosome. [9]

Relevant Symptoms Include: Primary ovarian insufficiency, larger than average stature, skeletal anomalies. [9] [10]

**Triple X Syndrome Karyotype**. Photo Credit: Kishore Behera, Jasmina Begum, Debasish Hota. www.researchgate.net/publication/350244416_Mosaicism_Triple_X_Syndrome_in_a_Young_Woman_Presenting_as_Primary_Amenorrhea_with_Short_Stature.

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I.1.D. Jacobs Syndrome (47 XYY): When a male has one extra Y chromosome. [11]

Relevant Symptoms Include: Many males with this condition have no or few noticeable symptoms. When symptoms do occur, they are usually the following: cryptorchidism, hypoplastic scrotum, micropenis, hypospadias, infertility, and possible emotional dysregulation (i.e. increased risk of aggressive behavior). [12] [13]

**Jacobs** **Syndrome** **Karyotype**. Photo Credit: Dimitrios Athanatos, Christos Tsakalidis, George Tampakoudis, Maria Papastergiou, Fillipos Tzevelekis, George Pados, Efstratios Assimakopoulos. www.ncbi.nlm.nih.gov/pmc/articles/PMC2769437.

I.2. Hormones & Gender:

In this section, we examine conditions that are caused by issues in response to hormones.

As always, people with atypical sex chromosome patterns can have a variety of experiences, symptoms, and phenotypes. Therefore, they may identify with a range of genders. Their personal identification may not necessarily align with the physical characteristics usually associated with their chromosomal pattern.

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I.2.A. Androgen Insensitivity Syndrome (AIS): When genetic males do not respond correctly to androgens. There are 3 possible results:

Complete AIS (CAIS): Biological males with mostly the physical characteristics of a female. [14]
Partial AIS (PAIS): Biological males with a mix of male and female physical characteristics. [14]
Mild AIS (MAIS): Biological males with mostly the physical characteristics of a male. [14]

Relevant Symptoms of CAIS Include: Mostly phenotypically female (female genitalia present), amenorrhea, underdeveloped labia and/or clitoris, shorter than average vaginal depth, gonadal dysgenesis (atrophic testes, missing ovaries), aromatized testosterone, presence of Skene’s gland, absence of the paramesonephric duct (fallopian tubes, uterus, upper vagina), infertility, vaginal hypoplasia. [14] [15] [16] [17] [18] [19] [20]

Relevant Symptoms of PAIS Include: Gynecomastia, high pitched voice, hypospadias, micropenis or clitoromegaly, small prostate, infertility, erectile dysfunction, anejaculation. [14] [16] [21]

Relevant Symptoms of MAIS Include: Gynecomastia, high pitched voice, hypospadias, micropenis, infertility, low ejaculate volume, low bitesticular volume. [14] [22]

**How an Androgen Receptor Works**: Testosterone (T) enters the cell, if 5-Alpha-Reductase is present, T is converted into Dihydrotestone (DHT). Upon binding to a steroid, the Androgen Receptor (AR) undergoes a conformational change and releases Heat Shock Proteins (hsps). Phosphorylation (P) occurs. The AR translocates to the nucleus where dimerization, DNA binding, and coactivators recruitment occurs. Target genes are transcribed and translated into proteins. [23] Photo Credit: Jonathan Marcus.

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I.2.B. Swyer Syndrome (XY Gonadal Dysgenesis): When genetic males do not respond to, or produce, testosterone, leading them to develop as females. [24]

Relevant Symptoms Include: Female external genitalia, small uterus, no gonads (ovaries or testes), amenorrhea. [25]

I.3. Genes & Gender:

In this section, we examine conditions that are caused by issues with chromosomes at a gene level.

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I.3.A. De La Chapelle Syndrome (XX Male Syndrome): When genetic females have a translocated gene, leading them to be phenotypically male. [26]

For this syndrome, let’s examine the mechanism of why this occurs.

In male development, the SRY gene is located on the Y chromosome. This gene is the main determinant of male development because it initiates the process of forming testes in the embryonic gonadal tissue. [26]
Once the testes are formed, they produce testosterone, leading to the development of other male physical characteristics. [26]
In cases of De La Chapelle Syndrome, during the formation of the sperm or egg, a piece of the Y chromosome containing the SRY gene attaches to an X chromosome. [26]
When an X chromosome carrying the SRY gene combines with a regular X chromosome from the other parent, the result is an XX chromosome set (a genetic female) with an SRY gene. [26]
Because of the SRY gene’s role in initiating male sexual development, the presence of this gene leads to the development of testes in the embryonic gonadal tissue, even though there’s no Y chromosome. [26]

Note: Not all cases of De La Chapelle Syndrome involve the SRY gene. There are some XX males without the SRY gene, suggesting other genes can also influence sex determination. This area is still being researched, and the exact mechanisms are not yet fully understood.

Those with De La Chapelle Syndrome are typically raised as males and are likely to have a male gender identity, despite being genetically female.

Relevant Symptoms Include: Hypospadias, micropenis or clitoromegaly, infertility, low libido, atrophic testes, cryptorchidism, gynecomastia, absence of the paramesonephric duct (fallopian tubes, uterus, upper vagina). [26] [27] [28] [29]

**De La Chapelle Analyses**: (C) Chromosome Analysis. (D) PCR Analysis and Karyotype. [30] Photo Credit: Min Kim, Pyoung Hwang, Dae-Yeol Lee. www.sciencedirect.com/science/article/pii/S1875957215000601.

I.4. Other Conditions:

There are many more conditions that resemble the previous ones written in Sections I.1 — I.3, here are just a few:

48 XXYY Syndrome. [31]
48 XYYY Syndrome (Note that this is not the same as Jacobs Syndrome). [32]
49 XXXXX Syndrome (Pentasomy X). [33]
49 XXXXY Syndrome. [34]
Mixed Gonadal Dysgenesis (MGD). [35]

Section I — Questions to Consider:

If a human doesn’t fall into the categories of having either XX or XY sex chromosomes, what is their gender? (Note that we’re not asking “What is their sex?”.)
Why should binary people have the privilege to enact legislation that: prescribes a gender to the aforementioned people, and/or determines appropriate behavior with regards to hormone treatments, gender reassignment, etc.?

Section II — Chromosomal Anomalies As Benevolent

One argument some people make against transgenderism is some variation of what follows:

If we “cure” all chromosomal variations, there would no longer be a scientific basis for supporting transgendered people in their treatments, rights, etc., since the remaining transgendered people would all have either XX or XY sex chromosomes.

This argument is flawed for multiple reasons. The first rebuttal (and the most elementary) is that the argument assumes that chromosomal variations need to be “cured”. It presupposes that people with these conditions are inherently problematic or need fixing. This perspective is not only stigmatizing but also overlooks the fact that these individuals, like anyone else, have unique value and contribute to the diversity of human experiences and to the gene pool itself. Many people with chromosomal variations live fulfilling lives and do not desire to be “cured.” More rebuttals are to follow.

II.1. Lessons From Sickle Cell Disease (SCD) & Malaria:

II.1.A. Overview of SCD:

SCD is a group of inherited red blood cell disorders. Healthy red blood cells (RBCs) are round. In someone who has SCD, the RBCs become hard, sticky, and become sickle shaped. [36]

The sickle cells die early, which causes a constant shortage of RBCs. Also, when they travel through blood vessels, they get stuck and clog the blood flow. This can cause pain and other serious problems such infection, acute chest syndrome, and stroke. [36]

SCD is caused by a mutation in the HBB gene, which provides instructions for making a component of hemoglobin. This mutation leads to the production of abnormal hemoglobin (hemoglobin S), which distorts red blood cells into a sickle shape under low-oxygen conditions. [36]

II.1.B. SCD As It Relates to Malaria:

Malaria is caused by a parasite that invades RBCs. Once inside these cells, the parasites reproduce, breaking down hemoglobin and using it as a food source. Eventually, they cause the RBCs to burst, releasing more parasites into the bloodstream, where they can invade more red blood cells and continue the cycle. [37]

People with Sickle Cell Trait (SCT) carry one copy of the abnormal allele of the hemoglobin beta gene, but do not display the severe symptoms of SCD that occur in a person who has two copies of that allele. With this trait, RBCs can become sickle-shaped under certain conditions, such as low oxygen levels. [36] [38]

Sickle-shaped cells are not as hospitable to the malaria parasites — they either can’t enter the cells as easily, or if they do enter, they can’t reproduce as effectively. Additionally, the immune system more readily recognizes and destroys the sickled cells, helping to clear the infection. [39]

Moreover, when the parasites are inside a sickle cell and the cell reverts back to a sickle shape, the cell often dies. This kills the parasite as well, interrupting the life cycle of the parasite and reducing the severity and spread of the malaria infection. [39] [40]

SCT provides protection against malaria, but it doesn’t provide complete immunity. People with SCT can still contract malaria, although the disease is often much less severe. The connection to malaria comes from observations that SCT is more common in regions where malaria is or was prevalent. [41] [43]

This theory is called the “heterozygote advantage,” which is a situation in which heterozygous people have a survival advantage over homozygous people. [42]

**Distribution Maps of SCT & Malaria**: (A) Distribution Map of SCT. (B) Distribution Map of Malaria. Photo Credit: Sachin Nuguru.

II.1.C. Chromosomal Anomalies and Genetic Diversity:

The existence of chromosomal disorders are generally not advantageous on an individual level (although it’s important to note that they occasionally can be advantageous). However, their existence can contribute to genetic diversity, which is crucial for the survival and adaptability of species. Here’s a few ways as to how this can happen:

Variation: Chromosomal abnormalities can introduce new variations into a population’s gene pool. These variations may not be advantageous in their extreme forms (like in Turner Syndrome), but less extreme variations or combinations with other genes could be beneficial. [49] [50]
Genetic Drift: Even neutral or slightly disadvantageous genes can persist in a population through genetic drift, which involves random changes in the frequencies of genes in a population.
Carrier Advantages: In some genetic disorders, being a carrier can offer certain advantages. We saw this in the previous section(s) as it relates to SCT. In this way, it’s plausible that genetic outliers in the population that occurred with SCT and SCD can have analogous outliers as it relates to sex chromosomal anomalies.

II.2. Genetic Diversity & The LGTBQ+ Community:

Evolution does not act with intent or foresight. It is a process guided by randomness, survival, and reproduction. Genetic diversity, including that introduced by LGBTQ+ individuals or chromosomal abnormalities, enhances a population’s ability to adapt to changing environments and survive as a species. [45]

While LGBTQ+ people might not always engage in reproductive behaviors that directly pass on their genes, they can still contribute significantly to genetic diversity in a few ways:

Kin Selection: This is the theory that some evolutionary trends favor the reproductive success of an organism’s relatives, sometimes at a cost to the organism’s own survival and reproduction. For instance, an LGBTQ+ person might help raise relatives, thereby promoting the survival of their shared genes. [44]
Balancing Selection: Some genes might have pleiotropy. It’s possible that the same genes that predispose individuals to be LGBTQ+ also confer other advantageous traits. If these advantages outweigh the potential decrease in direct reproduction, these genes will continue to exist in the population. [46]
Reproduction: Some LGBTQ+ people do engage in heterosexual relationships and have children. This contributes to genetic diversity.
Social Contributions: Many evolutionary biologists argue that the survival of a species is not just about passing on individual genes but also about maintaining social structures that support the healthy development of offspring. In this way, LGBTQ+ people contribute to the health and diversity of their social group and, indirectly, to genetic diversity. [47] [48]