{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T03:23:30Z","timestamp":1775705010731,"version":"3.50.1"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Symmetry"],"abstract":"<jats:p>Phenotypic variation arises from genetic and environmental variation, as well as random aspects of development. The genetic (nature) and environmental (nurture) components of this variation have been appreciated since at least 1900. The random developmental component (noise) has taken longer for quantitative geneticists to appreciate. Here, I sketch the historical development of the concepts of random developmental noise and developmental instability, and its quantification via fluctuating asymmetry. The unsung pioneers in this story are Hugo DeVries (fluctuating variation, 1909), C. H. Danforth (random variation between monozygotic twins, 1919), and Sewall Wright (random developmental variation in piebald guinea pigs, 1920). The first pioneering study of fluctuating asymmetry, by Sumner and Huestis in 1921, is seldom mentioned, possibly because it failed to connect the observed random asymmetry with random developmental variation. This early work was then synthesized by Boris Astaurov in 1930 and Wilhelm Ludwig in 1932, and then popularized by Drosophila geneticists beginning with Kenneth Mather in 1953. Population phenogeneticists are still trying to understand the origins and behavior of random developmental variation. Some of the developmental noise represents true stochastic behavior of molecules and cells, while some represents deterministic chaos, nonlinear feedback, and symmetry breaking.<\/jats:p>","DOI":"10.3390\/sym13071204","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T22:02:04Z","timestamp":1625522524000},"page":"1204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Nature, Nurture, and Noise: Developmental Instability, Fluctuating Asymmetry, and the Causes of Phenotypic Variation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1974-132X","authenticated-orcid":false,"given":"John H.","family":"Graham","sequence":"first","affiliation":[{"name":"Department of Biology, Berry College, Mount Berry, GA 30149, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"ref_1","unstructured":"Darwin, C. (1859). The Origin of Species, John Murray."},{"key":"ref_2","unstructured":"Darwin, C. (1868). Variation of Plants and Animals under Domestication, John Murray."},{"key":"ref_3","unstructured":"Falconer, D., and Mackay, T. (1996). Introduction to Quantitative Genetics, Longmans Green. [3rd ed.]."},{"key":"ref_4","unstructured":"Finch, C.E., and Kirkwood, T.B.L. (2000). Chance, Development, and Aging, Oxford University Press."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Polak, M. (2003). Developmental Instability and the Stochastic Component of Total Phenotypic Variance. Developmental Instability. Causes and Consequences, Oxford University Press.","DOI":"10.1093\/oso\/9780195143454.001.0001"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1258\/002367790780890347","article-title":"A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals?","volume":"24","year":"1990","journal-title":"Lab. Anim."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ashby, W.R. (1956). An Introduction to Cybernetics, Chapman and Hall.","DOI":"10.5962\/bhl.title.5851"},{"key":"ref_8","first-page":"7","article-title":"Population phenogenetics: Analysis of developmental stability in natural populations","volume":"191","author":"Zakharov","year":"1992","journal-title":"Acta Zool. Fenn."},{"key":"ref_9","unstructured":"Haecker, V. (1918). Entwicklungsgeschichtliche Eigenschaftsanalyse (Ph\u00e4nogenetik). Gemeinsame Aufgaben der Entwicklungsgeschichte, Vererbungs- und Rassenlehre, Gustav Fischer."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/15592294.2016.1277299","article-title":"Valentin Haecker (1864\u20131927) as a pioneer of phenogenetics: Building the bridge between genotype and phenotype","volume":"12","author":"Watts","year":"2017","journal-title":"Epigenetics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00438-018-1519-1","article-title":"100 Years of phenogenetics: Valentin Haecker and his examination of the phenotype","volume":"294","author":"Levit","year":"2019","journal-title":"Mol. Genet. Genom."},{"key":"ref_12","first-page":"1508","article-title":"On the ratio of components of phenotypic variances of bilateral characters in populations of some fishes","volume":"25","author":"Kozhara","year":"1989","journal-title":"Genetika"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1439-0426.1994.tb00156.x","article-title":"Phenotypic variance of bilateral characters as an indicator of genetic and environmental conditions in bream Abramis brama (L.) (Pisces, Cyprinidae) populations","volume":"10","author":"Kozhara","year":"1994","journal-title":"J. Appl. Ichthyol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cannon, W. (1932). The Wisdom of the Body, W.W. Norton & Company.","DOI":"10.1097\/00000441-193212000-00028"},{"key":"ref_15","unstructured":"Waddington, C.H. (1957). The Strategy of the Genes: A Discussion of Some Aspects of Theoretical Biology, George Allen Unwin."},{"key":"ref_16","first-page":"1","article-title":"Future prospects for population phenogenetics","volume":"4","author":"Zakharov","year":"1989","journal-title":"Sov. Sci. Rev. F Physiol. Gen. Biol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pigliucci, M. (2001). Phenotypic Plasticity: Beyond Nature and Nurture, Johns Hopkins University Press.","DOI":"10.56021\/9780801867880"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3390\/sym2020466","article-title":"Fluctuating asymmetry: Methods, theory, and applications","volume":"2","author":"Graham","year":"2010","journal-title":"Symmetry"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Graham, J.H., and \u00d6zener, B. (2016). Fluctuating asymmetry of human populations: A review. Symmetry, 8.","DOI":"10.3390\/sym8120154"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/nature01135","article-title":"Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans","volume":"419","author":"Herndon","year":"2002","journal-title":"Nature"},{"key":"ref_21","first-page":"566","article-title":"The history of twins, as a criterion of the relative powers of nature and nurture","volume":"12","author":"Galton","year":"1875","journal-title":"Fraser\u2019s Mag."},{"key":"ref_22","first-page":"80","article-title":"A theory of heredity","volume":"27","author":"Galton","year":"1875","journal-title":"Contemp. Rev. 1866\u20131900"},{"key":"ref_23","first-page":"285","article-title":"Mathematical contributions to the theory evolution\u2014IX. On principle of homotyposis and its relation, the variability of the individual, and to that of the race. Part I.\u2014Homotyposis in the vegetable Kingdom","volume":"197","author":"Pearson","year":"1901","journal-title":"Philos. Trans. R. Soc. London. Ser. A Contain. Pap. Math. Phys. Character"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/biomet\/1.3.320","article-title":"On the fundamental conceptions of biology","volume":"1","author":"Pearson","year":"1902","journal-title":"Biometrika"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1098\/rspl.1901.0099","article-title":"Heredity, differentiation, and other conceptions of biology: A consideration of Professor Karl Pearson\u2019s paper \u2018On the Principle of homotyposis\u2019","volume":"69","author":"Bateson","year":"1902","journal-title":"Proc. R. Soc. Lond."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gould, S.J. (2002). The Structure of Evolutionary Theory, Harvard University Press.","DOI":"10.4159\/9780674417922"},{"key":"ref_27","first-page":"258","article-title":"Note on variation in leaves of mulberry trees","volume":"1","author":"Fry","year":"1902","journal-title":"Biometrika"},{"key":"ref_28","first-page":"104","article-title":"On differentiation and homotyposis in the leaves of Fagus sylvatica","volume":"3","author":"Pearson","year":"1904","journal-title":"Biometrika"},{"key":"ref_29","first-page":"97","article-title":"Variation and correlation in the flowers of Lagerstroemia indica","volume":"1909","author":"Harris","year":"1909","journal-title":"Mo. Bot. Gard. Annu. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/biomet\/1.4.400","article-title":"The relation of binary fission to variation","volume":"1","author":"Simpson","year":"1902","journal-title":"Biometrika"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1086\/279572","article-title":"Variation, correlation and inheritance of fertility in the mammals","volume":"50","author":"Harris","year":"1916","journal-title":"Am. Nat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/biomet\/10.1.144","article-title":"On homotyposis and allied characters in eggs of the Common Tern","volume":"10","author":"Rowan","year":"1914","journal-title":"Biometrika"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/biomet\/12.3-4.308","article-title":"On the nest and eggs of the Common Tern (S. fluviatilis). A cooperative study","volume":"12","author":"Rowan","year":"1919","journal-title":"Biometrika"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"De Vries, H. (1909). The Mutation Theory; Experiments and Observations on the Origin of Species in the Vegetable Kingdom: The Origin of Species by Mutation, Open Court Publishing Company.","DOI":"10.5962\/bhl.title.4634"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"166","DOI":"10.2307\/1536658","article-title":"An apterous mutation in Bruchus","volume":"48","author":"Breitenbecher","year":"1925","journal-title":"Biol. Bull."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/genetics\/6.5.445","article-title":"Bilateral asymmetry and its relation to certain problems of genetics","volume":"6","author":"Sumner","year":"1921","journal-title":"Genetics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/oxfordjournals.jhered.a101956","article-title":"Resemblance and difference in twins: Twins that look and act alike attract attention first, while dissimilar ones are apt to be overlooked","volume":"10","author":"Danforth","year":"1919","journal-title":"J. Hered."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1073\/pnas.6.6.320","article-title":"The relative importance of heredity and environment in determining the piebald pattern of guinea-pigs","volume":"6","author":"Wright","year":"1920","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","first-page":"183","article-title":"Analyse der erblichen St\u00f6rungsf\u00e4lle der bilateralen Symmetrie","volume":"55","author":"Astaurov","year":"1930","journal-title":"Z. Indukt. Abstamm. Vererb."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2307\/2406192","article-title":"A study of fluctuating asymmetry","volume":"16","year":"1962","journal-title":"Evolution"},{"key":"ref_41","first-page":"247","article-title":"In commemoration of Boris L. Astaurov (1904\u20131974)","volume":"60","author":"Gaissinovitch","year":"1975","journal-title":"Cas. Morav. Mus. Acta Musei Moraviae. Vedy Prir. Sci. Nat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1086\/411444","article-title":"The life and research of Boris L. Astaurov","volume":"54","author":"Berg","year":"1979","journal-title":"Q. Rev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1093\/genetics\/12.2.128","article-title":"Studies on the phenotypic manifestation of hereditary factors. I. On the phenotypic manifestation of the genovariation radius incompletus in Drosophila funebris","volume":"12","year":"1927","journal-title":"Genetics"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ludwig, W. (1932). Das Rechts-Links Problem im Tierreich und Beim Menschen, Springer.","DOI":"10.1007\/978-3-662-29196-2"},{"key":"ref_45","first-page":"53","article-title":"\u00dcber den Einfluss des genotypischen Milieus und der Aussenbedingungen auf die Realisation des Genotyps: Genmutation vti (venae transversae imcompletae) bei Drosophila funebris","volume":"1","year":"1934","journal-title":"Nachr. G\u00f6ttingen Gesell Math Phys. KI"},{"key":"ref_46","unstructured":"Waddington, C.H. (1940). Organisers and Genes, Cambridge University Press."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/150563a0","article-title":"Canalization of development and the inheritance of acquired characters","volume":"150","author":"Waddington","year":"1942","journal-title":"Nature"},{"key":"ref_48","unstructured":"Schmalhausen, I.I. (1949). Factors of Evolution: The Theory of Stabilizing Selection, The Blakiston Co."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/hdy.1953.41","article-title":"Genetical control of stability in development","volume":"7","author":"Mather","year":"1953","journal-title":"Heredity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/1741109a0","article-title":"Stability in development and relational balance of X-chromosomes in Drosophila melanogaster","volume":"174","author":"Tebb","year":"1954","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Thoday, J.M. (1955). Balance, Heterozygosity and Developmental Stability. Cold Spring Harbor Symposia on Quantitative Biology, Spring Harbor Laboratory Press.","DOI":"10.1101\/SQB.1955.020.01.032"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/hdy.1958.41","article-title":"Homeostasis in a selection experiment","volume":"12","author":"Thoday","year":"1958","journal-title":"Heredity"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/hdy.1960.38","article-title":"Developmental stability in constant and fluctuating temperatures","volume":"14","author":"Beardmore","year":"1960","journal-title":"Heredity"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1017\/S0016672300000148","article-title":"Some genetic tests on asymmetry of sternopleural chaeta number in Drosophila","volume":"1","author":"Reeve","year":"1960","journal-title":"Genet. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1242\/jeb.39.2.251","article-title":"Maternal age and developmental variability","volume":"39","author":"Parsons","year":"1962","journal-title":"J. Exp. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/j.1601-5223.1960.tb03098.x","article-title":"Frequency of morphological deviants as a criterion of developmental stability","volume":"46","author":"Rasmuson","year":"1960","journal-title":"Hereditas"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1086\/282480","article-title":"Phenetics of natural populations. II. Asymmetry and evolution in a lizard","volume":"101","year":"1967","journal-title":"Am. Nat."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"396","DOI":"10.2307\/2407629","article-title":"Heterozygosity and developmental stability: Another look","volume":"33","year":"1979","journal-title":"Evolution"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1086\/286030","article-title":"Developmental stability and fitness: A review","volume":"149","year":"1997","journal-title":"Am. Nat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1017\/S1464793101005796","article-title":"Fluctuating asymmetry as an indicator of fitness: Can we bridge the gap between studies?","volume":"77","author":"Lens","year":"2002","journal-title":"Biol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Polak, M. (2003). Developmental instability: An appropriate indicator of plant fitness?. Developmental Instability: Causes and Consequences, Oxford University Press.","DOI":"10.1093\/oso\/9780195143454.001.0001"},{"key":"ref_62","unstructured":"Gleick, J. (1987). Chaos: Making a New Science, Penguin."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"279","DOI":"10.31887\/DCNS.2007.9.3\/coestreicher","article-title":"A history of chaos theory","volume":"9","author":"Oestreicher","year":"2007","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/BF01068142","article-title":"A third source of developmental differences","volume":"23","author":"Molenaar","year":"1993","journal-title":"Behav. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Markow, T.A. (1994). Antisymmetry, Directional Asymmetry, and Dynamic Morphogenesis. Developmental Instability: Its Origins and Evolutionary Implications, Kluwer.","DOI":"10.1007\/978-94-011-0830-0"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Polak, M. (2003). Nonlinear Dynamics and Developmental Instability. Developmental Instability: Causes and Consequences, Oxford University Press.","DOI":"10.1093\/oso\/9780195143454.001.0001"},{"key":"ref_67","unstructured":"Nicolis, G., and Prigogine, I. (1989). Exploring Complexity an Introduction, St. Martin\u2019s Press."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1103\/PhysRevA.38.364","article-title":"Self-organized criticality","volume":"38","author":"Bak","year":"1988","journal-title":"Phys. Rev. A"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"013108","DOI":"10.1063\/1.3675622","article-title":"Fractal variability: An emergent property of complex dissipative systems","volume":"22","author":"Seely","year":"2012","journal-title":"Chaos"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF02424507","article-title":"Nonlinear growth dynamics and the origin of fluctuating asymmetry","volume":"89","author":"Emlen","year":"1993","journal-title":"Genetica"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1063\/1.166355","article-title":"How organisms do the right thing: The attractor hypothesis","volume":"8","author":"Emlen","year":"1998","journal-title":"Chaos"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/BF02424508","article-title":"Developmental stability in plants: Symmetries, stress and epigenesis","volume":"89","author":"Freeman","year":"1993","journal-title":"Genetica"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Graham, J.H., Robb, D.T., and Poe, A.R. (2012). Random phenotypic variation of yeast (Saccharomyces cerevisiae) single-gene knockouts fits a double pareto-lognormal distribution. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048964"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/genetics\/120.1.213","article-title":"Diazinon resistance, fluctuating asymmetry and fitness in the Australian sheep blowfly, Lucilia cuprina","volume":"120","author":"McKenzie","year":"1988","journal-title":"Genetics"},{"key":"ref_75","first-page":"57","article-title":"Fluctuating asymmetry as a measure of developmental stability: Implications of non-normal distributions and power of statistical tests","volume":"191","author":"Palmer","year":"1992","journal-title":"Acta Zool. Fenn."}],"container-title":["Symmetry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-8994\/13\/7\/1204\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:26:16Z","timestamp":1760163976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-8994\/13\/7\/1204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":75,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["sym13071204"],"URL":"https:\/\/doi.org\/10.3390\/sym13071204","relation":{},"ISSN":["2073-8994"],"issn-type":[{"value":"2073-8994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,5]]}}}