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Review
. 2017 Jan 2;95(1-2):291-300.
doi: 10.1002/jnr.23884.

A general theory of sexual differentiation

Arthur P Arnold  1
Affiliations
Review

A general theory of sexual differentiation

Arthur P Arnold. J Neurosci Res. .

Abstract

A general theory of mammalian sexual differentiation is proposed. All biological sex differences are the result of the inequality in effects of the sex chromosomes, which are the only factors that differ in XX vs. XY zygotes. This inequality leads to male-specific effects of the Y chromosome, including expression of the testis-determining gene Sry that causes differentiation of testes. Thus, Sry sets up lifelong sex differences in effects of gonadal hormones. Y genes also act outside of the gonads to cause male-specific effects. Differences in the number of X chromosomes between XX and XY cells cause sex differences in expression (1) of Xist, (2) of X genes that escape inactivation, and (3) of parentally imprinted X genes. Sex differences in phenotype are ultimately the result of multiple, independent sex-biasing factors, hormonal and sex chromosomal. These factors act in parallel and in combination to induce sex differences. They also can offset each other to reduce sex differences. Other mechanisms, operating at the level of populations, cause groups of males to differ on average from groups of females. The theory frames questions for further study, and directs attention to inherent sex-biasing factors that operate in many tissues to cause sex differences, and to cause sex-biased protection from disease. © 2016 Wiley Periodicals, Inc.

Keywords: X chromosome; Y chromosome; estradiol; testosterone.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram showing the effects of five classes of sex-biasing factors discussed here. Each factor derives from the inherent inequality in sex chromosomes when comparing XX and XY cells, tissues, or animals. The factors can act independently to contribute to sex differences in phenotype. The intersection of arrows is intended to evoke the idea that sex-biasing factors can interact, either by augmenting or opposing each other within specific cells, or by acting on different cells that each contribute to sex differences in the phenotype. The sex-biased factors therefore can produce or reduce sex differences in phenotype. Sex differences can wax or wane depending on a variety of factors such as age or disease.
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References

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