The evolution of sex differences in disease.

Edward H Morrow

doi:10.1186/s13293-015-0023-0

Abstract

It is now becoming widely recognized that there are important sex differences in disease. These include rates of disease incidence, symptoms and age of onset. These differences between the sexes can be seen as a subset of the more general phenomenon of sexual dimorphism of quantitative phenotypes. From a genetic point of view, this is paradoxical, since the vast majority of genetic material is shared between the sexes. How can males and females differ in so many ways and yet have a common genetic code? Traditionally, the modifying action of hormones has been offered as a solution to this paradox, but experiments disentangling the effects of hormones and sex-chromosomes have shown that this cannot be the sole explanation. In this review, I outline current ideas about the evolutionary origins of sex differences in phenotypes, with a particular focus on how sex differences in disease can arise. I also discuss how sex differences in themselves can generate new risk factors for disease, in effect becoming a new environmental factor, as well as briefly reviewing more general evidence for sexually antagonistic selection and genetic variation within humans. Taking an evolutionary view on sex differences in disease provides an opportunity for greater understanding of mechanisms of disease and as such provides a clear motivation for clinicians to explore how therapies may be tailored to the individual in a sex-dependent way.

Highlights

In the inaugural article of Biology of Sex Differences [1], Arnold outlined the main motivations for why the existence of separate sexes is an important factor to consider when investigating human disease, the key point is that sex differences in human physiology exist and that they matter, both in terms of determining disease phenotypes and for shaping more effective therapies
Evolutionary theory can provide a conceptual framework within which sex differences in human physiological or disease phenotypes can be understood
Sex differences in themselves can act as risk factors for disease, but there is increasing evidence that genetics plays a role in contributing to quantitative traits and disease risk in contemporary human populations

Summary

Introduction

In the inaugural article of Biology of Sex Differences [1], Arnold outlined the main motivations for why the existence of separate sexes is an important factor to consider when investigating human disease, the key point is that sex differences in human physiology exist and that they matter, both in terms of determining disease phenotypes and for shaping more effective therapies. The mechanisms by which traits become sexually dimorphic, whether via sexual or natural selection, are still not fully resolved, evolutionary models have been proposed based on sex-specific differences in selection and changes to the genetic architecture [12].

Results

Conclusion