Genetics of Sexual Dimorphism in Humans


Sexual dimorphism describes the suite of morphological, physiological and behavioural phenotypes that distinguishes males and females. In humans, the determination of sex is triggered early in embryogenesis by the presence or absence of a Y chromosome and its SRY locus, prompting a regulatory cascade of genetic, epigenetic and hormonal changes. A distinct male and female genetic state precipitates the development of sexually dimorphic characters including primary and secondary sexual traits. Recent genomic studies have also found sexually dimorphic differences in gene expression across surveyed adult tissues that may be modulated by sex‐specific cis‐regulatory elements, alternative splicing and differentially methylated sites. Such sexual dimorphisms at both phenotypic and molecular levels have important implications in disease onset, progression and treatment. New molecular, genomic and clinical data mining tools are providing novel insight into the emerging field of gender medicine with a focus to understand sex differences in disease. Sexually dimorphic characters, starting with our earliest eukaryotic ancestors, can evolve via sexual conflict with direct and indirect consequences on the patterning of the genomic landscape.

Key Concepts

  • Anisogamy evolved early in eukaryotic evolution from an isogamous ancestor.
  • Human sex determination is based on the sex chromosome inherited from the father.
  • The presence or absence of the Y‐linked SRY locus triggers a cascade of genetic and hormonal signals in the early fetus.
  • Androgen and testosterone, among the initial hormones produced in the fetus, decide the sexual fate of the early gonads that eventually develop into primary reproductive organs found in the adult.
  • Secondary sexual characteristics that develop during puberty distinguish males from females at the morphological level.
  • Sex‐biased gene expression may be modulated by cis‐regulatory elements (CREs) and sex‐specific alternative splicing.
  • Differences in the male and female epigenomes include distinct methylated patterns such as imprinting and result in differential gene expression.
  • Sexual selection and sexual conflict may play a role in the origins and maintenance of sexually dimorphic traits.
  • Sexual dimorphism at the genetic and cellular levels is becoming an important focus of disease research owing to the recent policy shifts in government funding to address gender health disparities.

Keywords: disease; epigenomics; genomics; gonadal development; imprinting; reproduction; sexual selection; SRY


Andersson M (1994) Sexual Selection. Princeton, NJ: Princeton University Press.

Angelopoulou R, Lavranos G and Manolakou P (2006) Establishing sexual dimorphism in humans. Collegium Antropologicum 30: 653–658.

Arango NA, Lovell‐Badge R and Behringer RR (1999) Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development. Cell 99: 409–419.

Bonduriansky R (2007) The genetic architecture of sexual dimorphism: the potential roles of genomic imprinting and condition dependence. In: Fairbairn DJ, Blanckenhorn WU and Szekely T (eds) Sex, Size And Gender Roles: Evolutionary Studies of Sexual Size Dimorphism. Oxford: Oxford University Press.

Cesario SK and Hughes LA (2007) Precocious puberty: a comprehensive review of literature. Journal of Obstetric, Gynecologic, and Neonatal Nursing 36: 263–274.

Charlesworth B, Coyne JA and Barton NH (1987) The relative rates of evolution of sex chromosome and autosomes. American Naturalist 130: 113–146.

Choi BG and McLaughlin MA (2007) Why men's hearts break: cardiovascular effects of sex steroids. Endocrinology and Metabolism Clinics of North America 36: 365–377.

Clayton JA and Collins FS (2014) Policy: NIH to balance sex in cell and animal studies. Nature 509: 282–283.

Darwin CR (1871) The Descent of Man and Selection in Relation to Sex. London: John Murray.

D'Souza I, Poorkaj P, Hong M, et al. (1999) Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism‐chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements. Proceedings of the National Academy of Sciences of the United States of America 96: 5598–5603.

Deasy BM, Lu A, Tebbets JC, et al. (2007) A role for cell sex in stem cell‐mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency. Journal of Cell Biology 177: 73–86.

Dinsdale EC and Ward WE (2010) Early exposure to soy isoflavones and effects on reproductive health: a review of human and animal studies. Nutrients 11: 1156–1187. DOI: 10.3390/nu2111156

Dorak MT and Karpuzoglu E (2012) Gender differences in cancer susceptibility: an inadequately addressed issue. Frontiers in Genetics 28 (3): 268.

Du L, Bayir H, Lai Y, et al. (2004) Innate gender‐based proclivity in response to cytotoxicity and programmed cell death pathway. Journal of Biological Chemistry 279 (37): 38563–38570.

Fisher RA (1930) The Genetical Theory of Natural Selection. Clarendon Press: Oxford.

George J, Rapsomaniki E, Pujades‐Rodriguez M, et al. (2015) How does cardiovascular disease first present in women and men? Incidence of 12 cardiovascular diseases in a contemporary cohort of 1,937,360 people. Circulation 132: 1320–1328.

Graves JA (2006) Sex chromosome specialization and degeneration in mammals. Cell 124: 901–914.

Helena Mangs A and Morris BJ (2007) The human pseudoautosomal region (PAR): origin, function and future. Current Genomics 8: 129–136.

Khil PP, Smirnova NA, Romanienko PJ and Camerini‐Otero RD (2004) The mouse X chromosome is enriched for sex‐biased genes not subject to selection by meiotic sex chromosome inactivation. Nature Genetics 36: 642–646.

Lockshin MD (2006) Sex differences in autoimmune disease. Lupus 15: 753–756.

Luedi PP, Dietrich FS, Weidman JR, et al. (2007) Computational and experimental identification of novel human imprinted genes. Genome Research 17: 1723–1730.

Marshall Graves JA and Peichel CL (2010) Are homologies in vertebrate sex determination due to shared ancestry or to limited options? Genome Biology 11: 205.

Matlin AJ, Clark F and Smith CWJ (2005) Understanding alternative splicing: towards a cellular code. Nature Reviews. Molecular Cell Biology 6: 386–398.

Maynard Smith J (1978) The Evolution of Sex. Cambridge: Cambridge University Press.

Ober C, Loisel DA and Gilad Y (2008) Sex‐specific genetic architecture of human disease. Nature Reviews. Genetics 9: 911–922.

Parker GA, Baker RR and Smith VGF (1972) The origin and evolution of gamete dimorphism and the male–female phenomenon. Journal of Theoretical Biology 36: 529–553.

Parsch J and Ellegren H (2013) The evolutionary causes and consequences of sex‐biased gene expression. Nature Reviews. Genetics 14: 83–87.

Penaloza C, Estevez B, Orlanski S, et al. (2009) Sex of the cell dictates its response: differential gene expression and sensitivity to cell death inducing stress in male and female cells. The FASEB Journal 23: 186901879.

Pollitzer E (2013) Biology: cell sex matters. Nature 500: 23–24.

Rigby N and Kulathinal RJ (2015) Genetic architecture of sexual dimorphism in humans. J. Cell. Physiol. 230: 2304–2310. DOI: 10.1002/jcp.24979

Skaletsky H, Kuroda‐Kawaguchi T, Minx PJ, et al. (2003) The male‐specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423: 825–837.

Singmann P, Shem‐Tov D, Wahl S, et al. (2015) Characterization of whole‐genome autosomal differences of DNA methylation between men and women. Epigenetics & Chromatin 8: 43.

Trabzuni D, Ramasamy A, Imran S, et al. (2013) Widespread sex differences in gene expression and splicing in the adult human brain. Nature Communications 4: 2771.

Veerappa AM, Padakannaya P and Ramachandra NB (2013) Copy number variation‐based polymorphism in a new pseudoautosomal region 3 (PAR3) of a human X‐chromosome‐transposed region (XTR) in the Y chromosome. Functional and Integrative Genomics 13: 285–293.

Williams TM and Carroll SB (2009) Genetic and molecular insights into the development and evolution of sexual dimorphism. Nature Reviews. Genetics 10: 797–804.

Further Reading

Baggio G, Corsini A, Floreani A, Giannini S and Zagonel V (2013) Gender medicine: a task for the third millennium. Clinical Chemistry and Laboratory Medicine 51: 713–727.

Pollitzer E (2013) Biology: cell sex matters. Nature 500: 23–24.

NIH Office of Research on Women's Health (ORWH).‐and‐gender‐infographic/index.asp

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Kulathinal, Rob J(Dec 2016) Genetics of Sexual Dimorphism in Humans. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026634]