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

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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.


  1. 1.

    Fogel, R. The Escape from Hunger and Premature Mortality, 1750–2100 (Cambridge Univ. Press, 2004). This book by Robert Fogel, a recipient of the Nobel Prize in Economics, documents the remarkable changes in human stature that followed the nutritional and demographic transitions and the contributions made by these improvements in health to human economic development.

  2. 2.

    Landrigan, P. J. et al. The Lancet Commission on pollution and health. Lancet 391, 462–512 (2018).

  3. 3.

    Naghavi, M. et al. Global, regional, and national age-sex specific mortality for 264 causes of death: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390, 1151–1210 (2017).

  4. 4.

    Leeder, S., Raymond, S., Greenberg, H., Liu, H. & Esson, K. A race against time: the challenge of cardiovascular disease in developing countries. The Earth Institute Columbia University (2004).

  5. 5.

    Bloom, D. E. et al. The global economic burden of non-communicable diseases. World Economic Forum, Geneva (2011).

  6. 6.

    Lee, R. The demographic transition: three centuries of fundamental change. J. Econ. Persp. 17, 167–190 (2003). This is an excellent summary of the changes occurring across the demographic transition, including analyses of causes and consequences and yet-to-be-resolved uncertainties.

  7. 7.

    Allen, R. C. Poverty lines in history, theory, and current international practice. Oxford University Department of Economics Discussion Paper Series #685. Department of Economics (2013).

  8. 8.

    Clarke, G. A Farewell to Alms: A Brief Economic History of the World (Princeton Univ. Press, 2008).

  9. 9.

    Omran, A. R. The epidemiologic transition: a theory of the epidemiology of population change. Milbank Q. 49, 509–538 (1971). This paper initiated the analysis of connections between nutrition, disease and vital rates across the epidemiological transition.

  10. 10.

    Wrigley, E. & Schofield, R. The Population History of England 1541–1871; A Reconstruction (Oxford: Blackwell, 1981). This landmark work in historical demography charts population trends and demographic transition in England over more than 300 years.

  11. 11.

    Davenport, D. in Population Histories in Context: Past achievements and future directions. (Cambridge Group for the History of Population and Social Structure, Cambridge UK, 2014).

  12. 12.

    McKeown, T. Food, infection, and population. J. Interdiscip. Hist. 14, 227–247 (1983).

  13. 13.

    Schaible, U. E. & Kaufmann, S. H. E. Malnutrition and infection: complex mechanisms and global impacts. PLoS Med. 4, e115 (2007).

  14. 14.

    Scrimshaw, N. S. & SanGiovanni, J. P. Synergism of nutrition, infection, and immunity: an overview. Am. J. Clin. Nutr. 66, 464S–477S (1997).

  15. 15.

    Szreter, S. Industrialization and health. Br. Med. Bull. 69, 75–86 (2004).

  16. 16.

    Hamlin, C. & Sheard, S. Revolutions in public health: 1848 and 1998? BMJ 317, 587–591 (1998).

  17. 17.

    Riedel, S. Edward Jenner and the history of smallpox and vaccination. Proc. (Bayl. Univ. Med. Cent.) 18, 21–25 (2005).

  18. 18.

    Razzell, P. E. ‘An interpretation of the modern rise of population in Europe’ — a critique. Popul. Stud. (Camb.) 28, 5–17 (1974).

  19. 19.

    Landers, J. Death and the Metropolis: Studies in the Demographic History of London, 1670–1830 (Cambridge Univ. Press, 1993).

  20. 20.

    McKeown, R. E. The epidemiologic transition: changing patterns of mortality and population dynamics. Am. J. Lifestyle Med. 3 (Suppl. 1), 19S–26S (2009).

  21. 21.

    Oeppen, J. & Vaupel, J. W. Broken limits to life expectancy. Science 296, 1029–1031 (2002).

  22. 22.

    Gurven, M. & Kaplan, H. Longevity among hunter–gatherers: a cross-cultural examination. Popul. Dev. Rev. 33, 321–365 (2007).

  23. 23.

    Wilmoth, J. R., Deegan, L. J., Lundstrom, H. & Horiuchi, S. Increase of maximum life-span in Sweden, 1861–1999. Science 289, 2366–2368 (2000).

  24. 24.

    Wilmoth, J. R. & Robine, J.-M. The world trend in maximum life span. Popul. Dev. Rev. 29, 239–257 (2003).

  25. 25.

    The World Bank Group. Life expectancy at birth, total (years) for high-income countries. HealthStats (2018).

  26. 26.

    Olshansky, S. J. et al. A potential decline in life expectancy in the united states in the 21st century. N. Engl. J. Med. 352, 1138–1145 (2005).

  27. 27.

    Wilmoth, J. in Between Zeus and the Salmon: the Biodemography of Longevity (eds Wachter, K. W. & Finch, C. E.) 38–64 (National Academy Press, 1997).

  28. 28.

    Wood, J. W. Fecundity and natural fertility in humans. Oxf. Rev. Reprod. Biol. 11, 61–109 (1989).

  29. 29.

    Cowgill, U. Season of birth in man. Ecology 47, 614–623 (1966).

  30. 30.

    Wrigley, E., Davies, R., Oeppen, J. & Schofield, R. English Population History from Family Reconstitution (Cambridge Univ. Press, 1997).

  31. 31.

    Campbell, K. & Woods, J. in Natural Human Fertility: Social and Biological Determinants (eds Diggory, P., Potts, M. & Tepr, S.) (Macmillan Press, 1988).

  32. 32.

    Coale, A. in The Decline of Fertility in Europe (eds Coale, A. J. & Watkins, S. C.) 1–3 (Princeton Univ. Press, 1986).

  33. 33.

    Weir, D. R. Fertility transition in rural France, 1740–1829. J. Econ. Hist. 44, 612–614 (1984).

  34. 34.

    Wrigley, E. A. The fall of marital fertility in nineteenth-century France: exemplar or exception? (Part II). Eur. J. Popul. 1, 141–177 (1985).

  35. 35.

    Wrigley, E. A. The fall of marital fertility in nineteenth-century France: exemplar or exception? (Part I). Eur. J. Popul. 1, 31–60 (1985).

  36. 36.

    The World Bank Group. Birth rate, crude (per 1,000 people). HealthStats (2018).

  37. 37.

    Bongaarts, J. Fertility and reproductive preferences in post-transitional societies. Popul. Dev. Rev. 27, 260–281 (2001).

  38. 38.

    Schoenaker, D. A., Jackson, C. A., Rowlands, J. V. & Mishra, G. D. Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents. Int. J. Epidemiol. 43, 1542–1562 (2014).

  39. 39.

    Beets, G. in The Future of Motherhood in Western Societies: Late Fertility and its Consequences (eds Beets, G., Schippers, J. & te Velde, E. R.) 61–90 (Springer Netherlands, 2011).

  40. 40.

    Caldwell, J. Paths to lower fertility. BMJ 319, 985–987 (1999).

  41. 41.

    Balbo, N., Billari, F. C. & Mills, M. Fertility in advanced societies: a review of research: La fécondité dans les sociétés avancées: un examen des recherches. Eur. J. Popul. 29, 1–38 (2013).

  42. 42.

    World Health Organization. The top 10 causes of death. Fact sheet. Media Center (2017).

  43. 43.

    Wang, H. et al. Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390, 1084–1150 (2017).

  44. 44.

    Casper, M. et al. Changes in the geographic patterns of heart disease mortality in the United States: 1973 to 2010. Circulation 133, 1171–1180 (2016).

  45. 45.

    Ford, E. S. & Capewell, S. Proportion of the decline in cardiovascular mortality disease due to prevention versus treatment: public health versus clinical care. Annu. Rev. Public Health 32, 5–22 (2011).

  46. 46.

    Gakidou, E. et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390, 1345–1422 (2017).

  47. 47.

    Lloyd-Jones, D. et al. Heart disease and stroke statistics — 2010 update: a report from the American Heart Association. Circulation 121, e46–e215 (2010).

  48. 48.

    Williams, G. Pleiotropy, natural selection, and the evolution of senescence. Evolution 11, 398–411 (1957). This is the seminal paper proposing antagonistic pleiotropy as a mechanism that could explain ageing as the result of natural selection.

  49. 49.

    Risch, H. A. et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J. Natl Cancer Inst. 98, 1694–1706 (2006).

  50. 50.

    Neuhausen, S. L. et al. Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am. J. Hum. Genet. 58, 271–280 (1996).

  51. 51.

    Pavard, S. & Metcalf, C. J. Negative selection on BRCA1 susceptibility alleles sheds light on the population genetics of late-onset diseases and aging theory. PLoS ONE 2, e1206 (2007).

  52. 52.

    Smith, K. R., Hanson, H. A., Mineau, G. P. & Buys, S. S. Effects of BRCA1 and BRCA2 mutations on female fertility. Proc. Biol. Sci. 279, 1389–1395 (2012).

  53. 53.

    Ewertz, M. et al. Age at first birth, parity and risk of breast cancer: a meta-analysis of 8 studies from the nordic countries. Int. J. Cancer 46, 597–603 (1990).

  54. 54.

    Kang, H. J. et al. Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans. Proc. Natl Acad. Sci. USA 106, 9761–9766 (2009). This paper is among the first to find that the genetic variants that increase cancer risk may also confer benefits to fertility by improving the ability of zygotes to implant in the endometrium to initiate pregnancy.

  55. 55.

    Mahley, R. W. Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. J. Mol. Med. (Berl.) 94, 739–746 (2016).

  56. 56.

    Singh, P. P., Singh, M. & Mastana, S. S. APOE distribution in world populations with new data from India and the UK. Ann. Hum. Biol. 33, 279–308 (2006).

  57. 57.

    Oria, R. B. et al. APOE4 protects the cognitive development in children with heavy diarrhea burdens in Northeast Brazil. Pediatr. Res. 57, 310–316 (2005).

  58. 58.

    van Exel, E. et al. Effect of APOE ε4 allele on survival and fertility in an adverse environment. PLoS ONE 12, e0179497 (2017).

  59. 59.

    Engelaer, F. M., Koopman, J. J., van Bodegom, D., Eriksson, U. K. & Westendorp, R. G. Determinants of epidemiologic transition in rural Africa: the role of socioeconomic status and drinking water source. Trans. R. Soc. Trop. Med. Hyg. 108, 372–379 (2014).

  60. 60.

    Byars, S. G. et al. Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy. PLoS Genet. 13, e1006328 (2017).This paper reports a combination of recent signals of selection and pleiotropic effects on reproduction for the genetic variants most strongly associated with risk of CAD, providing strong evidence for antagonistic pleiotropy as the explanation for the origin and persistence of risk.

  61. 61.

    Rodríguez, J. A. et al. Antagonistic pleiotropy and mutation accumulation influence human senescence and disease. Nat. Ecol. Evol. 1, 55 (2017).

  62. 62.

    Barban, N. et al. Genome-wide analysis identifies 12 loci influencing human reproductive behavior. Nat. Genet. 48, 1462–14728 (2016).

  63. 63.

    Tropf, F. C. et al. Hidden heritability due to heterogeneity across seven populations. Nat. Hum. Behav. 1, 757–765 (2017).

  64. 64.

    Fisher, R. in The Genetical Theory of Natural Selection 22–47 (Oxford Univ. Press, 1930).

  65. 65.

    Crow, J. F. Some possibilities for measuring selection intensities in man. Hum. Biol. 30, 1–13 (1958).

  66. 66.

    Moorad, J. & Wade, M. Selection gradients, the opportunity for selection, and the coefficient of determination. Am. Nat. 181, 291–300 (2013).

  67. 67.

    Crow, J. Population genetics. Am. J. Hum. Genet. 13, 137–150 (1961).

  68. 68.

    Courtiol, A. et al. The demographic transition influences variance in fitness and selection on height and BMI in rural Gambia. Curr. Biol. 23, 884–889 (2013). This study documents changes in selection acting on morphological traits during rapid demographic transition in The Gambia, using data from a longitudinal multigenerational health study that has been ongoing for over 50 years.

  69. 69.

    Moorad, J., Promislow, D., Smith, K. & Wade, M. Mating system change reduces the strength of sexual selection in an American frontier population of the 19th century. Evol. Hum. Behav. 32, 147–155 (2011).

  70. 70.

    Gautam, R. Opportunity for natural selection among the Indian population: secular trend, covariates and implications. J. Biosoc. Sci. 41, 705–745 (2009).

  71. 71.

    Hed, H. Trends in opportunity for natural selection in the Swedish population during the period 1650–1980. Hum. Biol. 59, 785–797 (1987).

  72. 72.

    Moorad, J. Individual fitness and phenotypic selection in age-structured populations with constant growth rates. Ecology 95, 1087–1095 (2014).

  73. 73.

    Lande, R. A quantitative genetic theory of life-history evolution. Ecology 63, 607–615 (1982).

  74. 74.

    Moorad, J. A demographic transition altered the strength of selection for fitness and age-specific survival and fertility in a 19th century American population. Evolution 67, 1622–1634 (2013). This study describes how the strength of phenotypic selection for vital rates was affected by secular changes in mean fertility caused by a demographic transition.

  75. 75.

    Hamilton, W. Moulding of senescence by natural selection. J. Theor. Biol. 12, 12–45 (1966). This paper puts on a sound mathematical footing two hypotheses about the evolution of ageing — mutation accumulation and antagonistic pleiotropy.

  76. 76.

    Houle, D., Govindaraju, D. R. & Omholt, S. Phenomics: the next challenge. Nat. Rev. Genet. 11, 855–866 (2010).

  77. 77.

    Beauchamp, J. P. Genetic evidence for natural selection in humans in the contemporary United States. Proc. Natl Acad. Sci. USA 113, 7774–7779 (2016).

  78. 78.

    Conley, D. et al. Assortative mating and differential fertility by phenotype and genotype across the 20th century. Proc. Natl Acad. Sci. USA 113, 6647–6652 (2016).

  79. 79.

    Tropf, F. C. et al. Human fertility, molecular genetics, and natural selection in modern societies. PLoS ONE 10, e0126821 (2015).

  80. 80.

    Kong, A. et al. Selection against variants in the genome associated with educational attainment. Proc. Natl Acad. Sci. USA 114, E727–E732 (2017).This paper leverages Icelandic genomic data to estimate the direction of selection on educational attainment in a contemporary population: it is negative.

  81. 81.

    Moorad, J. A. & Walling, C. A. Measuring selection for genes that promote long life in a historical human population. Nat. Ecol. Evol. 1, 1773–1781 (2017).

  82. 82.

    Kohler, H. P., Rodgers, J. L. & Christensen, K. Between nurture and nature: the shifting determinants of female fertility in Danish twin cohorts. Soc. Biol. 49, 218–248 (2002).

  83. 83.

    Bolund, E., Hayward, A., Pettay, J. E. & Lummaa, V. Effects of the demographic transition on the genetic variances and covariances of human life-history traits. Evolution 69, 747–755 (2015).

  84. 84.

    Byars, S. G., Ewbank, D., Govindaraju, D. R. & Stearns, S. C. Natural selection in a contemporary human population. Proc. Natl Acad. Sci. USA 107 (Suppl. 1), 1787–1792 (2010). This is one of the papers that ignited interest in researching evolution in contemporary human populations.

  85. 85.

    Courtiol, A., Tropf, F. C. & Mills, M. C. When genes and environment disagree: making sense of trends in recent human evolution. Proc. Natl Acad. Sci. USA 113, 7693–7695 (2016).

  86. 86.

    Barrett, R. D. & Schluter, D. Adaptation from standing genetic variation. Trends Ecol. Evol. 23, 38–44 (2008).

  87. 87.

    Gibson, G. Rare and common variants: twenty arguments. Nat. Rev. Genet. 13, 135–145 (2012).

  88. 88.

    Campbell-Staton, S. C. et al. Winter storms drive rapid phenotypic, regulatory, and genomic shifts in the green anole lizard. Science 357, 495–498 (2017).

  89. 89.

    United Nations General Assembly. Political declaration of the high-level meeting of the general assembly on the prevention and control of non-communicable diseases. 66th Session Item 117. World Health Organization (2012).

  90. 90.

    Hermisson, J. & Pennings, P. S. Soft sweeps: molecular population genetics of adaptation from standing genetic variation. Genetics 169, 2335–2352 (2005).

  91. 91.

    Pritchard, J. K. & Di Rienzo, A. Adaptation — not by sweeps alone. Nat. Rev. Genet. 11, 665–667 (2010).

  92. 92.

    Field, Y. et al. Detection of human adaptation during the past 2000 years. Science 354, 760–764 (2016).This paper proposes the singleton density score (SDS), a new measure to infer signatures of recent selection from contemporary genomes.

  93. 93.

    Tishkoff, S. A. et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat. Genet. 39, 31–40 (2007).

  94. 94.

    Slatkin, M. A. Bayesian method for jointly estimating allele age and selection intensity. Genet. Res. 90, 129–137 (2008).

  95. 95.

    Nakagome, S. et al. Estimating the ages of selection signals from different epochs in human history. Mol. Biol. Evol. 33, 657–669 (2016).

  96. 96.

    Chen, H. & Slatkin, M. Inferring selection intensity and allele age from multilocus haplotype structure. G3 3, 1429–1442 (2013).

  97. 97.

    Roff, D. Evolution of Life Histories: Theory and Analysis (Chapman and Hall, 1992).

  98. 98.

    Stearns, S. The Evolution of Life Histories (Oxford Univ. Press, 1992).

  99. 99.

    Charlesworth, B. Evolution in Age-Structured Populations (Cambridge Univ. Press, 1994).

  100. 100.

    Keyfitz, N. & Fleiger, W. World Population: An Analysis of Vital Data (Univ. of Chicago Press, 1968).

  101. 101.

    Keyfitz, N. & Flieger, W. World Population Growth and Aging: Demographic Trends in the Late Twentieth Century (Univ. of Chicago Press, 1990).

  102. 102.

    Chin, l. & Van der Berg, B. A fertility table for the analysis of human reproduction. Math. Biosci. 62, 237–251 (1982).

  103. 103.

    Helle, S. A tradeoff between reproduction and growth in contemporary Finnish women. Evol. Hum. Behav. 29, 189–195 (2008).

  104. 104.

    Helle, S., Lummaa, V. & Jokela, J. Are reproductive and somatic senescence coupled in humans? Late, but not early, reproduction correlated with longevity in historical Sami women. Proc. Biol. Sci. 272, 29–37 (2005).

  105. 105.

    Kaar, P., Jokela, J., Helle, T. & Kojola, I. Direct and correlative phenotypic selection on life-history traits in three pre-industrial human populations. Proc. Biol. Sci. 263, 1475–1480 (1996).

  106. 106.

    Kirk, K. M. et al. Natural selection and quantitative genetics of life-history traits in western women: a twin study. Evolution 55, 423–435 (2001).

  107. 107.

    Weeden, J., Abrams, M. J., Green, M. C. & Sabini, J. Do high-status people really have fewer children? Education, income, and fertility in the contemporary US. Hum. Nature 17, 377–392 (2006).

  108. 108.

    Mealey, L. The relationship between social-status and biological success — a case-study of the Mormon religious hierarchy. Ethol. Sociobiol. 6, 249–257 (1985).

  109. 109.

    Moorad, J. A. Multi-level sexual selection: individual and family-level selection for mating success in a historical human population. Evolution 67, 1635–1648 (2013).

  110. 110.

    Bailey, S. M. & Garn, S. M. Socioeconomic interactions with physique and fertility. Hum. Biol. 51, 317–333 (1979).

  111. 111.

    Vetta, A. Fertility, physique, and intensity of selection. Hum. Biol. 47, 283–293 (1975).

  112. 112.

    Sear, R., Allal, N., Mace, R. & Mcgregor, I. Height and reproductive success among Gambian women. Am. J. Hum. Biol. 16, 223–223 (2004).

  113. 113.

    Nettle, D. Women’s height, reproductive success and the evolution of sexual dimorphism in modern humans. Proc. Biol. Sci. 269, 1919–1923 (2002).

  114. 114.

    Mueller, U. & Mazur, A. Evidence of unconstrained directional selection for male tallness. Behav. Ecol. Sociobiol. 50, 302–311 (2001).

  115. 115.

    Pawlowski, B., Dunbar, R. & Lipowicz, A. Evolutionary fitness — tall men have more reproductive success. Nature 403, 156–156 (2000).

  116. 116.

    Stearns, S.C. & Medzhitov, R. Evolutionary Medicine 1st edn Ch. 10 (Oxford University Press, 2016).

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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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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) doi:10.1038/s41576-018-0012-3

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