# Nature, Nurture, and Noise: Developmental Instability, Fluctuating Asymmetry, and the Causes of Phenotypic Variation

## Abstract

**:**

## 1. Introduction

## 2. Population Phenogenetics and Developmental Noise

#### 2.1. Developmental Homeostasis

#### 2.2. Symmetry and Asymmetry

## 3. Developmental Noise, Fluctuating Asymmetry, and Developmental Stability

#### 3.1. Nature, Nurture, and Noise

#### 3.2. Homotypic Correlation and Within-Individual Variation

#### 3.3. Fluctuating Variation

#### 3.4. Bilateral Asymmetry

#### 3.5. The Synthesis of Twin Studies and Asymmetry

#### 3.6. The Irregularity of Development

#### 3.7. Fluctuating Asymmetry

#### 3.8. Theory of Developmental Homeostasis

#### 3.9. Developmental Stability and the Drosophila Experimentalists

#### 3.10. Fluctuating Asymmetry in Natural Populations

#### 3.11. Chaos, Nonlinear Dynamics, and Systems Biology

## 4. Conclusions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Acknowledgments

## Conflicts of Interest

## References

- Darwin, C. The Origin of Species; John Murray: London, UK, 1859. [Google Scholar]
- Darwin, C. Variation of Plants and Animals under Domestication; John Murray: London, UK, 1868; Volume 1. [Google Scholar]
- Falconer, D.; Mackay, T. Introduction to Quantitative Genetics, 3rd ed.; Longmans Green: Harlow, Essex, UK, 1996. [Google Scholar]
- Finch, C.E.; Kirkwood, T.B.L. Chance, Development, and Aging; Oxford University Press: New York, NY, USA, 2000. [Google Scholar]
- Lajus, D.L.; Graham, J.H.; Kozhara, A.V. Developmental Instability and the Stochastic Component of Total Phenotypic Variance. In Developmental Instability. Causes and Consequences; Polak, M., Ed.; Oxford University Press: New York, NY, USA, 2003; pp. 343–363. [Google Scholar]
- Gärtner, K. 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? Lab. Anim.
**1990**, 24, 71–77. [Google Scholar] [CrossRef] [PubMed] - Ashby, W.R. An Introduction to Cybernetics; Chapman and Hall: London, UK, 1956. [Google Scholar]
- Zakharov, V.M. Population phenogenetics: Analysis of developmental stability in natural populations. Acta Zool. Fenn.
**1992**, 191, 7–30. [Google Scholar] - Haecker, V. Entwicklungsgeschichtliche Eigenschaftsanalyse (Phänogenetik). Gemeinsame Aufgaben der Entwicklungsgeschichte, Vererbungs- und Rassenlehre; Gustav Fischer: Jena, Germany, 1918. [Google Scholar]
- Hoßfeld, U.; Watts, E.; Levit, G.S. Valentin Haecker (1864–1927) as a pioneer of phenogenetics: Building the bridge between genotype and phenotype. Epigenetics
**2017**, 12, 247–253. [Google Scholar] [CrossRef] [PubMed] [Green Version] - Hoßfeld, U.; Levit, G.S.; Watts, E. 100 Years of phenogenetics: Valentin Haecker and his examination of the phenotype. Mol. Genet. Genom.
**2019**, 294, 445–456. [Google Scholar] [CrossRef] [PubMed] - Kozhara, A.V. On the ratio of components of phenotypic variances of bilateral characters in populations of some fishes. Genetika
**1989**, 25, 1508–1513. [Google Scholar] - Kozhara, A.V. Phenotypic variance of bilateral characters as an indicator of genetic and environmental conditions in bream Abramis brama (L.) (Pisces, Cyprinidae) populations. J. Appl. Ichthyol.
**1994**, 10, 167–181. [Google Scholar] [CrossRef] - Cannon, W. The Wisdom of the Body; W.W. Norton & Company: New York, NY, USA, 1932. [Google Scholar]
- Waddington, C.H. The Strategy of the Genes: A Discussion of Some Aspects of Theoretical Biology; George Allen Unwin: London, UK, 1957. [Google Scholar]
- Zakharov, V.M. Future prospects for population phenogenetics. Sov. Sci. Rev. F Physiol. Gen. Biol. Rev.
**1989**, 4, 1–79. [Google Scholar] - Pigliucci, M. Phenotypic Plasticity: Beyond Nature and Nurture; Johns Hopkins University Press: Baltimore, MD, USA, 2001. [Google Scholar]
- Graham, J.H.; Raz, S.; Hel-Or, H.; Nevo, E. Fluctuating asymmetry: Methods, theory, and applications. Symmetry
**2010**, 2, 466–540. [Google Scholar] [CrossRef] [Green Version] - Graham, J.H.; Özener, B. Fluctuating asymmetry of human populations: A review. Symmetry
**2016**, 8, 154. [Google Scholar] [CrossRef] [Green Version] - Herndon, L.A.; Schmeissner, P.J.; Dudaronek, J.M.; Brown, P.A.; Listner, K.M.; Sakano, Y.; Paupard, M.C.; Hall, D.H.; Driscoll, M. Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature
**2002**, 419, 808–814. [Google Scholar] [CrossRef] - Galton, F. The history of twins, as a criterion of the relative powers of nature and nurture. Fraser’s Mag.
**1875**, 12, 566–576. [Google Scholar] [CrossRef] [Green Version] - Galton, F. A theory of heredity. Contemp. Rev. 1866–1900
**1875**, 27, 80–95. [Google Scholar] [CrossRef] [Green Version] - Pearson, K.; Lee, A.; Warren, E.; Fry, A.; Fawcett, C.D. Mathematical contributions to the theory evolution—IX. On principle of homotyposis and its relation, the variability of the individual, and to that of the race. Part I.—Homotyposis in the vegetable Kingdom. Philos. Trans. R. Soc. London. Ser. A Contain. Pap. Math. Phys. Character
**1901**, 197, 285–379. [Google Scholar] - Pearson, K. On the fundamental conceptions of biology. Biometrika
**1902**, 1, 320–344. [Google Scholar] [CrossRef] - Bateson, W. Heredity, differentiation, and other conceptions of biology: A consideration of Professor Karl Pearson’s paper ‘On the Principle of homotyposis’. Proc. R. Soc. Lond.
**1902**, 69, 193–205. [Google Scholar] - Gould, S.J. The Structure of Evolutionary Theory; Harvard University Press: Cambridge, MA, USA, 2002. [Google Scholar]
- Fry, A. Note on variation in leaves of mulberry trees. Biometrika
**1902**, 1, 258. [Google Scholar] [CrossRef] - Pearson, K.; Radford, M. On differentiation and homotyposis in the leaves of Fagus sylvatica. Biometrika
**1904**, 3, 104–107. [Google Scholar] [CrossRef] - Harris, J.A. Variation and correlation in the flowers of Lagerstroemia indica. Mo. Bot. Gard. Annu. Rep.
**1909**, 1909, 97–104. [Google Scholar] [CrossRef] - Simpson, J.Y. The relation of binary fission to variation. Biometrika
**1902**, 1, 400–407. [Google Scholar] [CrossRef] - Harris, J.A. Variation, correlation and inheritance of fertility in the mammals. Am. Nat.
**1916**, 50, 626–636. [Google Scholar] [CrossRef] - Rowan, W.; Parker, K.M.; Bell, J. On homotyposis and allied characters in eggs of the Common Tern. Biometrika
**1914**, 10, 144–168. [Google Scholar] [CrossRef] - Rowan, W.; Wolff, E.; Sulman, P.L.; Pearson, K.; Isaacs, E.; Elderton, E.M.; Tildesley, M. On the nest and eggs of the Common Tern (S. fluviatilis). A cooperative study. Biometrika
**1919**, 12, 308–354. [Google Scholar] [CrossRef] - De Vries, H. 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: Chicago, IL, USA, 1909. [Google Scholar]
- Breitenbecher, J.K. An apterous mutation in Bruchus. Biol. Bull.
**1925**, 48, 166–170. [Google Scholar] [CrossRef] [Green Version] - Sumner, F.B.; Huestis, R.R. Bilateral asymmetry and its relation to certain problems of genetics. Genetics
**1921**, 6, 445–485. [Google Scholar] [CrossRef] - Danforth, C.H. Resemblance and difference in twins: Twins that look and act alike attract attention first, while dissimilar ones are apt to be overlooked. J. Hered.
**1919**, 10, 399–409. [Google Scholar] [CrossRef] - Wright, S. The relative importance of heredity and environment in determining the piebald pattern of guinea-pigs. Proc. Natl. Acad. Sci. USA
**1920**, 6, 320–332. [Google Scholar] [CrossRef] [Green Version] - Astaurov, B.L. Analyse der erblichen Störungsfälle der bilateralen Symmetrie. Z. Indukt. Abstamm. Vererb.
**1930**, 55, 183–262. [Google Scholar] [CrossRef] - Van Valen, L. A study of fluctuating asymmetry. Evolution
**1962**, 16, 125–142. [Google Scholar] [CrossRef] - Gaissinovitch, A.E. In commemoration of Boris L. Astaurov (1904–1974). Cas. Morav. Mus. Acta Musei Moraviae. Vedy Prir. Sci. Nat.
**1975**, 60, 247–252. [Google Scholar] - Berg, R.L. The life and research of Boris L. Astaurov. Q. Rev. Biol.
**1979**, 54, 397–416. [Google Scholar] [CrossRef] [PubMed] - Timofeeff-Ressovsky, N. Studies on the phenotypic manifestation of hereditary factors. I. On the phenotypic manifestation of the genovariation radius incompletus in Drosophila funebris. Genetics
**1927**, 12, 128–198. [Google Scholar] [CrossRef] - Ludwig, W. Das Rechts-Links Problem im Tierreich und Beim Menschen; Springer: Berlin, Germany, 1932. [Google Scholar]
- Timofeeff-Ressovsky, N.W. Über den Einfluss des genotypischen Milieus und der Aussenbedingungen auf die Realisation des Genotyps: Genmutation vti (venae transversae imcompletae) bei Drosophila funebris. Nachr. Göttingen Gesell Math Phys. KI
**1934**, 1, 53–104. [Google Scholar] - Waddington, C.H. Organisers and Genes; Cambridge University Press: Cambridge, UK, 1940. [Google Scholar]
- Waddington, C.H. Canalization of development and the inheritance of acquired characters. Nature
**1942**, 150, 563–565. [Google Scholar] [CrossRef] - Schmalhausen, I.I. Factors of Evolution: The Theory of Stabilizing Selection; The Blakiston Co.: Philadelphia, PA, USA, 1949. [Google Scholar]
- Mather, K. Genetical control of stability in development. Heredity
**1953**, 7, 297–336. [Google Scholar] [CrossRef] [Green Version] - Tebb, G.; Thoday, J.M. Stability in development and relational balance of X-chromosomes in Drosophila melanogaster. Nature
**1954**, 174, 1109–1110. [Google Scholar] [CrossRef] - Thoday, J.M. Balance, Heterozygosity and Developmental Stability. In Cold Spring Harbor Symposia on Quantitative Biology; Spring Harbor Laboratory Press: Cold Spring Harbor, NY, USA, 1955; pp. 318–326. [Google Scholar]
- Thoday, J.M. Homeostasis in a selection experiment. Heredity
**1958**, 12, 401–415. [Google Scholar] [CrossRef] [Green Version] - Beardmore, J. Developmental stability in constant and fluctuating temperatures. Heredity
**1960**, 14, 411–422. [Google Scholar] [CrossRef] - Reeve, E. Some genetic tests on asymmetry of sternopleural chaeta number in Drosophila. Genet. Res.
**1960**, 1, 151–172. [Google Scholar] [CrossRef] - Parsons, P.A. Maternal age and developmental variability. J. Exp. Biol.
**1962**, 39, 251–260. [Google Scholar] [CrossRef] - Rasmuson, M. Frequency of morphological deviants as a criterion of developmental stability. Hereditas
**1960**, 46, 511–535. [Google Scholar] [CrossRef] - Soulé, M. Phenetics of natural populations. II. Asymmetry and evolution in a lizard. Am. Nat.
**1967**, 101, 141–160. [Google Scholar] [CrossRef] - Soulé, M.E. Heterozygosity and developmental stability: Another look. Evolution
**1979**, 33, 396–401. [Google Scholar] [CrossRef] [PubMed] - Møller, A.P. Developmental stability and fitness: A review. Am. Nat.
**1997**, 149, 916–932. [Google Scholar] [CrossRef] [PubMed] - Lens, L.; Van Dongen, S.; Kark, S.; Matthysen, E. Fluctuating asymmetry as an indicator of fitness: Can we bridge the gap between studies? Biol. Rev.
**2002**, 77, 27–38. [Google Scholar] [CrossRef] [Green Version] - Tracy, M.; Freeman, D.C.; Duda, J.J.; Miglia, K.J.; Graham, J.H.; Hough, R.A. Developmental instability: An appropriate indicator of plant fitness? In Developmental Instability: Causes and Consequences; Polak, M., Ed.; Oxford University Press: New York, NY, USA, 2003; pp. 196–212. [Google Scholar]
- Gleick, J. Chaos: Making a New Science; Penguin: New York, NY, USA, 1987. [Google Scholar]
- Oestreicher, C. A history of chaos theory. Dialogues Clin. Neurosci.
**2007**, 9, 279–289. [Google Scholar] - Molenaar, P.C.; Boomsma, D.I.; Dolan, C.V. A third source of developmental differences. Behav. Genet.
**1993**, 23, 519–524. [Google Scholar] [CrossRef] [Green Version] - Graham, J.H.; Freeman, D.C.; Emlen, J.M. Antisymmetry, Directional Asymmetry, and Dynamic Morphogenesis. In Developmental Instability: Its Origins and Evolutionary Implications; Markow, T.A., Ed.; Kluwer: Dordrecht, The Netherlands, 1994; pp. 123–139. [Google Scholar]
- Graham, J.H.; Emlen, J.M.; Freeman, D.C. Nonlinear Dynamics and Developmental Instability. In Developmental Instability: Causes and Consequences; Polak, M., Ed.; Oxford University Press: New York, NY, USA, 2003; pp. 35–49. [Google Scholar]
- Nicolis, G.; Prigogine, I. Exploring Complexity an Introduction; St. Martin’s Press: New York, NY, USA, 1989. [Google Scholar]
- Bak, P.; Tang, C.; Wiesenfeld, K. Self-organized criticality. Phys. Rev. A
**1988**, 38, 364–374. [Google Scholar] [CrossRef] - Seely, A.J.E.; Macklem, P. Fractal variability: An emergent property of complex dissipative systems. Chaos
**2012**, 22, 013108. [Google Scholar] [CrossRef] - Emlen, J.M.; Freeman, D.C.; Graham, J.H. Nonlinear growth dynamics and the origin of fluctuating asymmetry. Genetica
**1993**, 89, 77–96. [Google Scholar] [CrossRef] - Emlen, J.M.; Freeman, D.C.; Mills, A.; Graham, J.H. How organisms do the right thing: The attractor hypothesis. Chaos
**1998**, 8, 717–726. [Google Scholar] [CrossRef] - Freeman, D.C.; Graham, J.H.; Emlen, J.M. Developmental stability in plants: Symmetries, stress and epigenesis. Genetica
**1993**, 89, 97–119. [Google Scholar] [CrossRef] - Graham, J.H.; Robb, D.T.; Poe, A.R. Random phenotypic variation of yeast (Saccharomyces cerevisiae) single-gene knockouts fits a double pareto-lognormal distribution. PLoS ONE
**2012**, 7, e48964. [Google Scholar] [CrossRef] [Green Version] - McKenzie, J.A.; Clarke, G.M. Diazinon resistance, fluctuating asymmetry and fitness in the Australian sheep blowfly, Lucilia cuprina. Genetics
**1988**, 120, 213–220. [Google Scholar] [CrossRef] - Palmer, A.R.; Strobeck, C. Fluctuating asymmetry as a measure of developmental stability: Implications of non-normal distributions and power of statistical tests. Acta Zool. Fenn.
**1992**, 191, 57–72. [Google Scholar]

**Figure 1.**Simple model of the relationship between genotype, environment, developmental noise, and phenotype.

**Figure 2.**Number of bristles on right (filled circles) and left (open circles) sides of an individual myriopod, Geophilus ferrugineus. The smoothed line shows the trend from anterior to posterior segments. Redrawn from Astaurov [39].

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |

© 2021 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

## Share and Cite

**MDPI and ACS Style**

Graham, J.H.
Nature, Nurture, and Noise: Developmental Instability, Fluctuating Asymmetry, and the Causes of Phenotypic Variation. *Symmetry* **2021**, *13*, 1204.
https://doi.org/10.3390/sym13071204

**AMA Style**

Graham JH.
Nature, Nurture, and Noise: Developmental Instability, Fluctuating Asymmetry, and the Causes of Phenotypic Variation. *Symmetry*. 2021; 13(7):1204.
https://doi.org/10.3390/sym13071204

**Chicago/Turabian Style**

Graham, John H.
2021. "Nature, Nurture, and Noise: Developmental Instability, Fluctuating Asymmetry, and the Causes of Phenotypic Variation" *Symmetry* 13, no. 7: 1204.
https://doi.org/10.3390/sym13071204