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The transition to modernity and chronic disease: mismatch and natural selection


The Industrial Revolution and the accompanying nutritional, epidemiological and demographic transitions have profoundly changed human ecology and biology, leading to major shifts in life history traits, which include age and size at maturity, age-specific fertility and lifespan. Mismatch between past adaptations and the current environment means that gene variants linked to higher fitness in the past may now, through antagonistic pleiotropic effects, predispose post-transition populations to non-communicable diseases, such as Alzheimer disease, cancer and coronary artery disease. Increasing evidence suggests that the transition to modernity has also altered the direction and intensity of natural selection acting on many traits, with important implications for public and global health.

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Fig. 1: Total fertility rate and life expectancy in selected countries before and after the demographic transition to modernity.
Fig. 2: Changes in vital rates and population growth across the demographic transition in England and Wales, 1551–2011.
Fig. 3: The epidemiological transition to modernity.
Fig. 4: The demographic transition to modernity.
Fig. 5: The costs and benefits of antagonistic pleiotropy, before and after the transition to modernity.
Fig. 6: The opportunities for mortality (I m ), fertility (I f ) and total selection (I t ) in England, 1541–1991.


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The authors thank the Wissenschaftskolleg zu Berlin for providing the time and space that allowed S.C., V.L., A.C. and S.S. to start their collaboration and the Academy of Finland for supporting V.L. They also thank I. Rickard for comments on early drafts of this paper.

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Nature Reviews Genetics thanks H. Snieder and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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The authors contributed equally to all aspects of the article.

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Correspondence to Stephen Stearns.

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Industrial Revolution

Period of time in Europe and North America in the late 1700s to early 1800s that saw the mechanization of agriculture and textile manufacturing and a revolution in the use of power that produced steamships and railroads, with profound impacts on social, cultural and economic conditions.

Demographic transitions

Transitions that result from changes in birth and death rates that yield dramatic, qualitative changes in population age distributions.


The historical period that started with the Industrial Revolution and then experienced the ecological, demographic and epidemiological transitions that led up to and include the present.

Life history traits

Traits directly associated with reproduction and survival, including size at birth, growth rate, age and size at maturity, number of offspring, frequency of reproduction and lifespan.

Antagonistic pleiotropy

A single gene has positive effects on fitness through its impact on one trait or age class but negative effects on fitness through its impact on another trait or age class.

Non-communicable diseases

Also known as chronic diseases, these diseases, which are characterized by slow progression and long duration, include cancer, cardiovascular diseases, chronic respiratory diseases, diabetes mellitus and dementias, such as Alzheimer disease.


The property of an individual in one generation that reflects its representation in subsequent generations.

Natural selection

The difference between the trait mean before and after weighting it by fitness; also, the covariation between a trait and fitness.

Lifetime reproductive success

The number of children per parent per lifetime, also called children ever born (CEB) or number of ever born (NEB). It is a measure of fitness that combines survival and reproduction.

Positive selection

Type of natural selection that increases the frequency of alleles contributing to reproductive success in a population.

Phenotypic evolution

The change in trait value distributions from one generation to the next.


The proportion of the variation in a phenotypic trait that is due to inherited variation among individuals in a population.

Additive genetic variation

The portion of the total genetic variation for a trait (not influenced by dominance or epistasis) that is capable of responding to selection.

Phenotypic plasticity

The sensitivity of the developing phenotype to differences in the environment.

Genetic drift

Random change in allele frequencies due to chance factors that occurs in populations of all sizes and can become strong enough to overshadow selection in small populations.

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Corbett, S., Courtiol, A., Lummaa, V. et al. The transition to modernity and chronic disease: mismatch and natural selection. Nat Rev Genet 19, 419–430 (2018).

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