Integrated phenotypes: Understanding trait covariation in plants and animals

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 369, Issue 1649, 2014, Pages

  Armbruster, W Scott ^a,b,c   Pélabon, Christophe ^c   Bolstad, Geir H ^c   Hansen, Thomas F ^d  

^a UNIVERSITY OF PORTSMOUTH   (United Kingdom)

^b UNIVERSITY OF ALASKA FAIRBANKS   (United States)

^c NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^d UNIVERSITY OF OSLO   (Norway)

Author keywords

Integration; Modularity; Phenotype; Variation

Indexed keywords

ALLOMETRY; ANIMAL; COEVOLUTION; EVOLUTIONARY THEORY; HOMOLOGY; INDEX METHOD; LIFE HISTORY TRAIT; NATURAL SELECTION; PHENOTYPE; PLANT;

ANATOMY AND HISTOLOGY; ANIMAL; BIOLOGICAL MODEL; EVOLUTION; FLOWER; PHENOTYPE; PHYSIOLOGY; PLANT PHYSIOLOGY; PROCEDURES; SYSTEMS BIOLOGY;

ANIMALS; BIOLOGICAL EVOLUTION; FLOWERS; MODELS, BIOLOGICAL; PHENOTYPE; PLANT PHYSIOLOGICAL PHENOMENA; SYSTEMS BIOLOGY;

EID: 84925230777     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2013.0245     Document Type: Review

References (207)

1. Hallgrímsson B, Hall BK. 2005 Variation: a central concept in biology. Burlington, MA: Elsevier.
2. Hallgrímsson B, Hall BK. 2011 Epigenetics: linking genotype and phenotype in development and evolution. Berkeley, MA: University of California Press.
3. Herrera CM. 2009 Multiplicity in unity. Chicago, IL: University Chicago Press.
4. Darwin C. 1859/1872 The origin of species, 1st edn/6th edn. London, UK: Murray.
5. Olson EC, Miller RJ. 1958 Morphological integration. Chicago, IL: University of Chicago Press.
6. Chernoff B, Magwene PM. 1999 Afterward. Morphological integration: forty years later. In Morphological integration (eds EC Olson, RL Miller), pp. 319-353. Chicago, IL: University of Chicago Press.
7. Murren CJ. 2012 The integrated phenotype. Integr. Comp. Biol. 52, 64-76. (doi: 10. 1093/icb/ics043).
8. Hallgrímsson B, Jamniczky H, Young NM, Rolian C, Parsons TE, Boughner JC, Marcucio RS. 2009 Deciphering the palimpsest: studying the relationship between morphological integration and phenotypic covariation. Evol. Biol. 36, 355-376. (doi: 10. 1007/s11692-009-9076-5).
9. Klingenberg C. 2008 Morphological integration and developmental modularity. Annu. Rev. Ecol. Evol. Syst. 39, 115-132. (doi: 10. 1146/annurev. ecolsys.37. 091305. 110054).
10. Von Dassow G, Munro E. 1999 Modularity in animal development and evolution: elements of a conceptual framework for EvoDevo. J. Exp. Zool. 285, 307-325. (doi: 10. 1002/(SICI)1097-010X(1999 1215)285: 4, 307:: AID-JEZ2. 3. 0. CO; 2-V).
11. Mitteroecker P, Bookstein F. 2007 The conceptual and statistical relationship between modularity and morphological integration. Syst. Biol. 56, 818-836. (doi: 10. 1080/10635150701648029).
12. Raff RA. 1996 The shape of life: genes, development, and the evolution of animal form. Chicago, IL: University Chicago Press.
13. Wagner GP, Altenberg L. 1996 Complex adaptations and the evolution of evolvability. Evolution 50, 967-976. (doi: 10. 2307/2410639).
14. Lewontin RC. 1978 Adaptation. Sci. Am. 239, 212-231. (doi: 10. 1038/scientificamerican 0978-212).
15. Schluter D. 1996 Adaptive radiation along genetic lines of least resistance. Evolution 50, 1766-1774. (doi: 10. 2307/2410734).
16. Gould SJ. 1977 Ontogeny and phylogeny. Cambridge, MA: Belknap Press.
17. Voje KJ, Hansen TF, Egset CK, Bolstad GH, Pélabon C. 2014 Allometric constraints and the evolution of allometry. Evolution 68, 866-885. (doi: 10. 1111/evo. 12312).
18. Firmat C, Lozano-Fernández I, Agustí J, Bolstad GH, Cuenca-Bescós G, Hansen TF, Pélabon C. 2014 Walk the line: 600 000 years of molar evolution constrained by allometry in the fossil rodent Mimomys savini. Phil. Trans. R. Soc. B 369, 20140057. (doi: 10. 1098/rstb. 2014. 0057).
19. Vallejo-Marín M, Walker C, Friston-Reilly P, Solís-Montero L, Igic B. 2014 Recurrent modification of floral morphology in heterantherous Solanum reveals a parallel shift in reproductive strategy. Phil. Trans. R. Soc. B 369, 20130256. (doi: 10. 1098/rstb. 2013. 0256).
20. Pélabon C, Firmat C, Bolstad GH, Voje KL, Houle D, Cassara J, Le Rouzic A, Hansen TF. In press. Evolution of morphological allometry. Ann. NY Acad. Sci. (doi: 10. 1111/nyas. 12470).
21. Kemp TS. 2007 The origin of higher taxa: macroevolutionary processes, and the case of the mammals. Acta Zool. 88, 3-22. (doi: 10. 1111/j. 1463-6395. 2007. 00248. x).
22. Hansen TF, Armbruster WS, Carlson ML, Pélabon C. 2003 Evolvability and genetic constraint in Dalechampia blossoms: genetic correlations and conditional evolvability. J. Exp. Zool. Mol. Dev. Evol. B 296, 23-39. (doi: 10. 1002/jez. b. 14).
23. Hansen TF. 2003 Is modularity necessary for evolvability? Remarks on the relationship between pleiotropy and evolvability. Biosystems 69, 83-94. (doi: 10. 1016/S0303-2647(02)00132-6).
24. Pavlicev M, Hansen TF. 2011 Genotype-phenotype maps maximizing evolvability: modularity revisited. Evol. Biol. 38, 371-389. (doi: 10. 1007/s11692-011-9136-5).
25. Gould SJ. 2002 The structure of evolutionary theory. Cambridge, MA: Belknap Press.
26. Riedl R. 1978 Order in living organisms: a systems analysis of evolution. New York, NY: Wiley.
27. Tedin O. 1925 Vererbung, Variation, und Systematik in der gattung Camelina. Hereditas 6, 275-386. (doi: 10. 1111/j. 1601-5223. 1925. tb03143. x).
28. Terentjev PV. 1931 Biometrische Untersuchungen über die morphologischen Merkmale von Rana ridibunda Pall. (Amphibian, Salientia). Biometrika 23, 23-51.
29. Stebbins GL. 1950 Variation and evolution in plants. New York, NY: Columbia University Press.
30. Berg RL. 1959 A general evolutionary principle underlying the origin of developmental homeostasis. Am. Nat. 93, 103-105. (doi: 10. 1086/282061).
31. Berg RL. 1960 The ecological significance of correlation pleiades. Evolution 14, 171-180. (doi: 10. 2307/2405824).
32. Van Valen L. 1965 The study of morphological integration. Evolution 19, 347-349. (doi: 10. 2307/2406444).
33. Cheverud JM. 1982 Phenotypic, genetic, and environmental integration in the cranium. Evolution 44, 520-538.
34. Cheverud JM. 1984 Quantitative genetics and developmental constraints on evolution by natural selection. J. Theor. Biol. 110, 155-172. (doi: 10. 1016/S0022-5193(84)80050-8).
35. Cheverud JM. 1996 Developmental integration and the evolution of pleiotropy. Am. Zool. 36, 44-50.
36. Wagner GP. 1996 Homologues, natural kinds and the evolution of modularity. Am. Zool. 36, 36-43.
37. Huxley JS. 1932 Problems of relative growth. New York, NY: Dial Press.
38. Gould SJ. 1966 Allometry and size in ontogeny and phylogeny. Biol. Rev. 41, 587-638. (doi: 10. 1111/j. 1469-185X. 1966. tb01624. x).
39. Klingenberg C. 1998 Heterochrony and allometry: the analysis of evolutionary change in ontogeny. Biol. Rev. 73, 79-123. (doi: 10. 1017/S000632319800512X).
40. Emlen DJ, Nijhout HF. 2000 The development and evolution of exaggerated morphologies in insects. Annu. Rev. Entomol. 45, 661-708. (doi: 10. 1146/annurev. ento. 45. 1. 661).
41. Bonduriansky R. 2007 Sexual selection and allometry: a critical reappraisal of the evidence and ideas. Evolution 61, 838-849. (doi: 10. 1111/j. 1558-5646. 2007. 00081. x).
42. Eberhard WG. 2009 Static allometry and animal genitalia. Evolution 63, 48-66. (doi: 10. 1111/j. 1558-5646. 2008. 00528. x).
43. Frankino WA, Emlen DJ, Shingleton AW. 2009 Experimental approaches to studying the evolution of animal form. In Experimental evolution: concepts, methods, and applications of selection experiments (eds T Garland, MR Rose), pp. 419-478. Berkeley, CA: University of California Press.
44. Van Noordwijk A, De Jong G. 1986 Acquisition and allocation of resources: their influence on variation in life history tactics. Am. Nat. 128, 137-142. (doi: 10. 1086/284547).
45. Charlesworth B. 1990 Optimization models, quantitative genetics, and mutation. Evolution 44, 520-538. (doi: 10. 2307/2409433).
46. Houle D. 1991 Genetic covariance of fitness correlates: what genetic correlations are made of and why it matters. Evolution 45, 630-648. (doi: 10. 2307/2409916).
47. Fry JD. 1993 The 'general vigor' problem: can antagonistic pleiotropy be detected when genetic covariances are positive? Evolution 47, 327-333. (doi: 10. 2307/2410143).
48. Mitteroecker P, Gunz P, Neubauer S, Müller G. 2012 How to explore morphological integration in human evolution and development? Evol. Biol. 39, 536-553. (doi: 10. 1007/s11692-012-9178-3).
49. Emlen DJ, Allen C. 2004 Genotype to phenotype: physiological control of trait size and scaling in insects. Integr. Comp. Biol. 634, 617-634.
50. Flatt T, Tu MP, Tatar M. 2005 Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. Bioessays 27, 999-1010. (doi: 10. 1002/bies. 20290).
51. Flatt T, Heyland A. 2011 Mechanisms of life history evolution: the genetics and physiology of life history traits and trade-offs. Oxford, UK: Oxford University Press.
52. Shingleton AW, Frankino WA, Flatt T, Nijhout HF, Emlen DJ. 2007 Size and shape: the developmental regulation of static allometry in insects. Bioessays 29, 536-548. (doi: 10. 1002/bies. 20584).
53. Nijhout HF. 2011 Dependence of morphometric allometries on the growth kinetics of body parts. J. Theor. Biol. 288, 35-43. (doi: 10. 1016/j. jtbi. 2011.08. 008).
54. Parker J. 2011 Morphogens, nutrients, and the basis of organ scaling. Evol. Dev. 13, 304-314. (doi: 10. 1111/j. 1525-142X. 2011. 00481. x).
55. Pélabon C, Bolstad GH, Egset CK, Cheverud JM, Pavlicev M, Rosenqvist G. 2013 On the relationship between ontogenetic and static allometry. Am. Nat. 181, 195-212. (doi: 10. 1086/668820).
56. Riska B. 1986 Some models for development, growth, and morphometric correlation. Evolution 40, 1303-1311. (doi: 10. 2307/2408955).
57. Slatkin M. 1987 Quantitative genetics of heterochrony. Evolution 41, 799-811. (doi: 10. 2307/2408889).
58. Wagner GP. 1989 Multivariate mutation-selection balance with constrained pleiotropic effects. Genetics 122, 223-234.
59. Houle D. 2001 Characters as the units of evolutionary change. In The character concept in evolutionary biology (ed. GP Wagner), pp. 109-140. New York, NY: Academic Press.
60. Rice SH. 2004 Developmental associations between traits: covariance and beyond. Genetics 166, 513-526. (doi: 10. 1534/genetics. 166. 1. 513).
61. Conner J, Via S. 1993 Patterns of phenotypic and genetic correlations among morphological and lifehistory traits in wild radish, Raphanus raphanistrum. Evolution 47, 704-711. (doi: 10. 2307/2410086).
62. Armbruster WS, Schwaegerle KE. 1996 Causes of covariation of phenotypic traits among populations. J. Evol. Biol. 9, 261-276. (doi: 10. 1046/j. 1420-9101. 1996. 9030261. x).
63. Armbruster WS, Pélabon C, Hansen TF, Mulder CPH. 2004 Floral integration and modularity: distinguishing complex adaptations from genetic constraints. In Phenotypic integration. Studying the ecology and evolution of complex phenotypes (eds M Pigliucci, KA Preston), pp. 23-49. Oxford, UK: Oxford University Press.
64. Mitteroecker P. 2009 The developmental basis of variational modularity: insights from quantitative genetics, morphometrics, and developmental biology. Evol. Biol. 36, 377-385. (doi: 10. 1007/s11692-009-9075-6).
65. Zelditch ML, Swiderski DL. 2011 Epigenetic interactions: the developmental route to functional integration. In Epigenetics: linking genotype and phenotype in development and evolution (eds B Hallgrimsson, BK Hall), pp. 290-316. Berkeley, CA: University of California Press.
66. Layzer D. 1980 Genetic variation and progressive evolution. Am. Nat. 115, 809-826. (doi: 10. 1086/283602).
67. Bürger R. 2000 The mathematical theory of selection, recombination, and mutation. Chichester, UK: Wiley.
68. Wagner GP, Booth G, Bagheri-Chaichian H. 1997 A population genetic theory of canalization. Evolution 51, 329-347. (doi: 10. 2307/2411105).
69. Rice SH. 1998 The evolution of canalization and the breaking of von Baer's laws: modeling the evolution of development with epistasis. Evolution 52, 647-656. (doi: 10. 2307/2411260).
70. Flatt T. 2005 The evolutionary genetics of canalization. Q. Rev. Biol. 80, 287-316. (doi: 10. 1086/432265).
71. Carter AJR, Hermisson J, Hansen TF. 2005 The role of epistatic gene interactions in the response to selection and the evolution of evolvability. Theor. Popul. Biol. 68, 179-196. (doi: 10. 1016/j. tpb. 2005.05. 002).
72. Hansen TF, Alvarez-Castro JM, Carter AJR, Hermisson J, Wagner GP. 2006 Evolution of genetic architecture under directional selection. Evolution 60, 1523-1536. (doi: 10. 1111/j. 0014-3820. 2006. tb00498. x).
73. Waddington CH. 1942 Canalization of development and the inheritance of acquired characters. Nature 150, 563-565. (doi: 10. 1038/150563a0).
74. Le Rouzic A, Álvarez-Castro JM, Hansen TF. 2013 The evolution of canalization and evolvability in stable and fluctuating environments. Evol. Biol. 40, 317-340. (doi: 10. 1007/s11692-012-9218-z).
75. Hermisson J, Hansen TF, Wagner GP. 2003 Epistasis in polygenic traits and the evolution of genetic architecture under stabilizing selection. Am. Nat. 161, 708-734. (doi: 10. 1086/374204).
76. Proulx SR, Phillips PC. 2005 The opportunity for canalization and the evolution of genetic networks. Am. Nat. 165, 147-162. (doi: 10. 1086/426873).
77. Jones AG, Arnold SJ, Bürger R. 2007 The mutation matrix and the evolution of evolvability. Evolution 61, 727-745. (doi: 10. 1111/j. 1558-5646. 2007. 00071. x).
78. Draghi J, Wagner GP. 2008 Evolution of evolvability in a developmental model. Evolution 62, 301-315. (doi: 10. 1111/j. 1558-5646. 2007. 00303. x).
79. Hansen TF. 2011 Epigenetics: adaptation or contingency? In Epigenetics: linking genotype and phenotype in development and evolution (eds B Hallgrimsson, BK Hall), pp. 357-376. Berkeley, CA: University of California Press.
80. Guillaume F, Otto SP. 2012 Gene functional tradeoffs and the evolution of pleiotropy. Genetics 192, 1389. (doi: 10. 1534/genetics. 112. 143214).
81. Rueffler C, Hermisson J, Wagner GP. 2012 Evolution of functional specialization and division of labor. Proc. Natl Acad. Sci. USA 109, E326-E335. (doi: 10. 1073/pnas. 1110521109).
82. Cheverud JM. 2001 The genetic architecture of pleiotropic relations and differential epistasis. In The character concept in evolutionary biology (ed. GP Wagner), pp. 411-433. San Diego, CA: Academic Press.
83. Pavlicev M, Kenney-Hunt JP, Norgard EA, Roseman CC, Wolf JB, Cheverud JM. 2008 Genetic variation in pleiotropy: differential epistasis as a source of variation in the allometric relationship between long bone lengths and body weight. Evolution 62, 199-213. (doi: 10. 1111/j. 1558-5646. 2007. 00255. x).
84. Pavlicev M, Norgard EA, Fawcett GI, Cheverud JM. 2011 Evolution of pleiotropy: epistatic interaction pattern supports a mechanistic model underlying variation in genotype-phenotype map. J. Exp. Zool. B (Mol. Dev. Evol.) 316, 371-385. (doi: 10. 1002/jez. b. 21410).
85. Force A, Cresko WA, Pickett FB, Proulx SR, Amemiya C, Lynch M. 2005 The origin of subfunctions and modular gene regulation. Genetics 170, 433-446. (doi: 10. 1534/genetics. 104. 027607).
86. Force A, Lynch M, Pickett FB, Amores A, Yan Y-L, Postlethwait J. 1999 Preservation of duplicate genes by complementary degenerative mutations. Genetics 151, 1531-1545.
87. Wray GA, Hahn MW, Abouheif E, Balhoff JP, Pizer M, Rockman MV, Romano LA. 2003 The evolution of transcriptional regulation in Eukaryotes. Mol. Biol. Evol. 20, 1377-1419. (doi: 10. 1093/molbev/msg140).
88. Pavlicev M, Cheverud JM, Wagner GP. 2011 Evolution of adaptive phenotypic variation patterns by direct selection for evolvability. Proc. R. Soc. B 278, 1903-1912. (doi: 10. 1098/rspb. 2010. 2113).
89. Gerhart J, Kirschner M. 1997 Cells, embryos and evolution: towards a cellular and developmental understanding of phenotypic variation and evolutionary adaptability. San Francisco, CA: Blackwell.
90. Armbruster WS, Hansen TF, Pélabon C, Pérez-Barrales R, Maad J. 2009 The adaptive accuracy of flowers: measurement and microevolutionary patterns. Ann. Bot. 103, 1529-1545. (doi: 10. 1093/aob/mcp095).
91. Pélabon C, Armbruster WS, Hansen TF, Bolstad G, Pérez-Barrales R. 2012 Adaptive accuracy and adaptive landscapes. In The adaptive landscape in evolutionary biology (eds EL Svensson, R Calsbeek), pp. 150-168. Oxford, UK: Oxford University Press.
92. de Visser JAGM et al. 2003 Evolution and detection of genetic robustness. Evolution 57, 1959-1972. (doi: 10. 1554/02-750R).
93. Rifkin SA, Houle D, Kim J, White KP. 2005 A mutation accumulation assay reveals a broad capacity for rapid evolution of gene expression. Nature 438, 220-223. (doi: 10. 1038/nature04114).
94. Lynch M. 2007 The frailty of adaptive hypotheses for the origins of organismal complexity. Proc. Natl Acad. Sci. USA 104, 8597-8604. (doi: 10. 1073/pnas. 0702207104).
95. Lynch M. 2007 The origins of genome architecture. Sunderland, MA: Sinauer.
96. Klingenberg CP. 2005 Developmental constraints, modules, and evolvability. In Variation, a central concept in biology (eds B Hallgrimsson, BK Hall), pp. 219-248. Amsterdam, The Netherlands: Elsevier.
97. Marquez EJ. 2008 A statistical framework for testing modularity in multidimensional data. Evolution 62, 2688-2708. (doi: 10. 1111/j. 1558-5646. 2008. 00476. x).
98. Klingenberg C. 2009 Morphometric integration and modularity in configurations of landmarks: tools for evaluating a priori hypotheses. Evol. Dev. 11, 405-421. (doi: 10. 1111/j. 1525-142X. 2009. 00347. x).
99. Polly PD. 2008 Developmental dynamics and Gmatrices: can morphometric space be used to model phenotypic evolution? Evol. Biol. 35, 83-96. (doi: 10. 1007/s11692-008-9020-0).
100. Goswami A, Polly PD. 2010 Methods for studying morphological integration and modularity. In Quantitative methods in paleobiology (eds J Alroy, G Hunt), pp. 213-243. Boulder, CO: The Paleontological Society.
101. Cheverud JM, Hartman SE, Richtsmeier JT, Atchley WR. 1991 A quantitative genetic analysis of localized morphology in mandibles of inbred mice using finite-element scaling analysis. J. Craniofacial Genet. Dev. Biol. 11, 122-137.
102. Cheverud JM, Routman EJ, Irschick DJ. 1997 Pleiotropic effects of individual gene loci on mandibular morphology. Evolution 51, 2006-2016. (doi: 10. 2307/2411021).
103. Cheverud JM, Ehrich TH, Vaughn TT, Koreishi SF, Linsey RB, Pletscher LS. 2004 Pleiotropic effects on mandibular morphology II: differential epistasis and genetic variation in morphological integration. J. Exp. Zool. B 302, 424-435. (doi: 10. 1002/jez. b. 21008).
104. Mezey JG, Cheverud J, Wagner G. 2000 Is the genotype-phenotype map modular? An approach using quantitative trait locus (QTL) data. Genetics 156, 305-311.
105. Klingenberg CP, Leamy LJ. 2001 Quantitative genetics of geometric shape in the mouse mandible. Evolution 55, 2342-2352. (doi: 10. 1111/j. 0014-3820. 2001. tb00747. x).
106. Zelditch ML, Wood AR, Swiderski DL. 2009 Building developmental integration into functional systems: function-induced integration of mandibular shape. Evol. Biol. 36, 71-87. (doi: 10. 1007/s11692-008-9034-7).
107. Klingenberg CP, Leamy LJ, Cheverud JM. 2004 Integration and modularity of quantitative trait locus effects on geometric shape in the mouse mandible. Genetics 166, 1909-1921. (doi: 10. 1534/genetics. 166. 4. 1909).
108. Brakefield PM. 2001 Structure of a character and the evolution of butterfly eyespot patterns. J. Exp. Zool. 291, 93-104. (doi: 10. 1002/jez. 1062).
109. Brakefield PM, Roskam JC. 2006 Exploring evolutionary constraints is a task for an integrative evolutionary biology. Am. Nat. 168, S4-S13. (doi: 10. 1086/509049).
110. Breuker CJ, Gibbs M, Van Dyck H, Brakefield PM, Klingenberg CP, Van Dongen S. 2007 Integration of wings and their eyespots in the speckled wood butterfly Pararge aegeria. J. Exp. Zool. B 308, 454-463. (doi: 10. 1002/jez. b. 21171).
111. Beldade P, French V, Brakefield PM. 2008 Developmental and genetic mechanisms for evolutionary diversification of serial repeats: eyespot size in Bicyclus anynana butterflies. J. Exp. Zool. B 310, 191-201. (doi: 10. 1002/jez. b. 21173).
112. Held LI. 2013 Rethinking butterfly eyespots. Evol. Biol. 40, 158-168. (doi: 10. 1007/s11692-012-9198-z).
113. Young NM, Hallgrimsson B. 2005 Serial homology and the evolution of mammalian limb covariation structure. Evolution 59, 2691-2704. (doi: 10. 1111/j. 0014-3820. 2005. tb00980. x).
114. Rolian C. 2009 Integration and evolvability in primate hands and feet. Evol. Biol. 36, 100-117. (doi: 10. 1007/s11692-009-9049-8).
115. Rolian C, Lieberman DE, Hallgrimsson B. 2010 The coevolution of human hands and feet. Evolution 64, 1558-1568. (doi: 10. 1111/j. 1558-5646. 2009. 00944. x).
116. Young NM, Wagner GP, Hallgrimsson B. 2010 Development and the evolvability of human limbs. Proc. Natl Acad. Sci. USA 107, 3400-3405. (doi: 10. 1073/pnas. 0911856107).
117. Grabowski MW, Polk JD, Roseman CC. 2011 Divergent patterns of integration and reduced constraint in the human hip and the origins of bipedalism. Evolution 65, 1336-1356. (doi: 10. 1111/j. 1558-5646. 2011. 01226. x).
118. Grabowski MW. 2013 Hominin obstetrics and the evolution of constraints. Evol. Biol. 40, 57-75. (doi: 10. 1007/s11692-012-9174-7).
119. Cheverud JM. 1995 Morphological integration in the saddle-back tamarin (Saguinus fuscicollis) cranium. Am. Nat. 145, 63-89. (doi: 10. 1086/285728).
120. Marroig G, Cheverud JM. 2001 A comparison of phenotypic variation and covariation patterns and the role of phylogeny. Ecology, and ontogeny during cranial evolution of New World monkeys. Evolution 55, 2576-2600. (doi: 10. 1111/j. 0014-3820. 2001. tb00770. x).
121. Mitteroecker P, Bookstein F. 2008 The evolutionary role of modularity and integration in the hominoid cranium. Evolution 62, 943-958. (doi: 10. 1111/j. 1558-5646. 2008. 00321. x).
122. Martinez-Abadiaz N, Esparza M, Sjovold T, Gonzales-Jose R, Santos M, Hernandez M. 2009 Heritability of human cranial dimensions: comparing the evolvability of different cranial regions. J. Anat. 214, 19-35. (doi: 10. 1111/j. 1469-7580. 2008. 01015. x).
123. Martinez-Abadiaz N, Mitteroecker P, Parsons TE, Esparza M, Sjovold T, Rolian C, Richtsmeier JT, Hallgrímsson B. 2012 The developmental basis of quantitative craniofacial variation in humans and mice. Evol. Biol. 39, 554-567. (doi: 10. 1007/s11692-012-9210-7).
124. Klingenberg CP, Zaklan SD. 2000 Morphological integration between developmental compartments in the Drosophila wing. Evolution 54, 1273-1285. (doi: 10. 1111/j. 0014-3820. 2000. tb00560. x).
125. McGuigan K, Blows MW. 2007 The phenotypic and genetic covariance structure of drosphilid wings. Evolution 61, 902-911. (doi: 10. 1111/j. 1558-5646. 2007. 00078. x).
126. Pélabon C, Hansen TF, Carter AJR, Houle D. 2006 Response of fluctuating and directional asymmetry to selection on wing shape in Drosophila melanogaster. J. Evol. Biol. 19, 764-776. (doi: 10. 1111/j. 1420-9101. 2005. 01054. x).
127. Pélabon C, Hansen TF, Carter AJR, Houle D. 2010 Evolution of variation and variability under fluctuating, stabilizing, and disruptive selection. Evolution 64, 1912-1925. (doi: 10. 1111/j. 1558-5646. 2010. 00979. x).
128. Klingenberg CP, Badyaev AV, Sowry SM, Beckwith NJ. 2001 Inferring developmental modularity from morphological integration: analysis of individual variation and asymmetry in bumblebee wings. Am. Nat. 157, 11-23. (doi: 10. 1086/317002).
129. Mezey JG, Houle D. 2005 The dimensionality of genetic variation for wing shape in Drosophila melanogaster. Evolution 59, 1027-1038. (doi: 10. 1111/j. 0014-3820. 2005. tb01041. x).
130. Conner JK, Lande R. 2014 Raissa L. Berg's contributions to the study of phenotypic integration, with a professional biographical sketch. Phil. Trans. R. Soc. B 369, 20130250. (doi: 10. 1098/rstb. 2013. 0250).
131. Armbruster WS, Di Stilio VS, Tuxill JD, Flores TC, Velasquez Runk JL. 1999 Covariance and decoupling of floral and vegetative traits in nine neotropical plants: a reevaluation of Berg's correlation-pleiades concept. Am. J. Bot. 86, 39-55. (doi: 10. 2307/2656953).
132. ArmbrusterWS, Hansen TF, Pélabon C, Bolstad GH. 2009 Macroevolutionary patterns of pollination accuracy: a comparison of three genera. New Phytol. 183, 600-617. (doi: 10. 1111/j. 1469-8137. 2009. 02930. x).
133. Stebbins GL. 1951 Natural selection and the differentiation of angiosperm families. Evolution 5, 299-324. (doi: 10. 2307/2405676).
134. Stebbins GL. 1974 Plant species. Evolution above the species level. Cambridge, MA: Harvard University Press.
135. Armbruster WS. 2014 Floral specialization and angiosperm diversity: phenotypic divergence, fitness trade-offs and realized pollination accuracy. AoB Plants 6, plu003. (doi: 10. 1093/aobpla/plu003).
136. Armbruster WS, Edwards ME, Debevec EM. 1994 Floral character displacement generates assemblage structure of Western Australian triggerplants (Stylidium). Ecology 75, 315-329. (doi: 10. 2307/1939537).
137. Ordano M, Fornoni J, Boege K, Dominguez D. 2008 The adaptive value of phenotypic floral integration. New Phytol. 179, 1183-1192. (doi: 10. 1111/j. 1469-8137. 2008. 02523. x).
138. Diggle PK. 2014 Modularity and intra-floral integration in metameric organisms: plants are more than the sum of their parts. Phil. Trans. R. Soc. B 369, 20130253. (doi: 10. 1098/rstb. 2013. 0253).
139. Rosas-Guerrero V, Quesada M, Armbruster WS, Pérez-Barrales R, Smith SD. 2011 Influence of pollination specialization and breeding system on floral integration and phenotypic variation in Ipomoea. Evolution 65, 350-364. (doi: 10. 1111/j. 1558-5646. 2010. 01140. x).
140. Pélabon C, Armbruster WS, Hansen TF. 2011 Experimental evidence for the Berg hypothesis: vegetative traits are more sensitive than pollination traits to environmental variation. Funct. Ecol. 25, 247-257. (doi: 10. 1111/j. 1365-2435. 2010. 01770. x).
141. Conner JK, Cooper IA, La Rosa RJ, Pérez SG, Royer AM. 2014 Patterns of phenotypic correlations among morphological traits across plants and animals. Phil. Trans. R. Soc. B 369, 20130246. (doi: 10. 1098/rstb. 2013. 0246).
142. Goswami A, Smaers JB, Soligo C, Polly PD. 2014 The macroevolutionary consequences of phenotypic integration: from development to deep time. Phil. Trans. R. Soc. B 369, 20130254. (doi: 10. 1098/rstb. 2013. 0254).
143. Klingenberg CP. 2014 Studying morphological integration and modularity at multiple levels: concepts and analysis. Phil. Trans. R. Soc. B 369, 20130249. (doi: 10. 1098/rstb. 2013. 0249).
144. Armbruster WS. 1991 Multilevel analyses of morphometric data from natural plant populations: insights into ontogenetic, genetic, and selective correlations in Dalechampia scandens. Evolution 45, 1229-1244. (doi: 10. 2307/2409730).
145. Armbruster WS. 1988 Multilevel comparative analysis of morphology, function, and evolution of Dalechampia blossoms. Ecology 69, 1746-1761. (doi: 10. 2307/1941153).
146. Bell G. 1989 A comparative method. Am. Nat. 133, 553-571. (doi: 10. 1086/284935).
147. Heisler IL, Damuth J. 1987 A method for analyzing selection in hierarchically structured populations. Am. Nat. 130, 582-602. (doi: 10. 1086/284732).
148. Bolstad GH, Armbruster WS, Pélabon C, Pérez-Barrales R, Hansen TF. 2010 Direct selection at the blossom level on floral reward by pollinators in a natural population of Dalechampia schottii: fulldisclosure honesty? New Phytol. 188, 370-384. (doi: 10. 1111/j. 1469-8137. 2010. 03429. x).
149. Armbruster WS. 1990 Estimating and testing the shapes of adaptive surfaces: the morphology and pollination of Dalechampia blossoms. Am. Nat. 135, 14-31. (doi: 10. 1086/285029).
150. Armbruster WS, Antonsen L, Pélabon C. 2005 Phenotypic selection on Dalechampia blossoms: honest signaling affects pollination success. Ecology 86, 3323-3333. (doi: 10. 1890/04-1873).
151. Pérez-Barrales R, Bolstad GH, Pélabon C, Hansen TF, Armbruster WS. 2013 Pollinators and seed predators generate conflicting selection on Dalechampia blossoms. Oikos 122, 1411-1428.
152. Cheverud JM. 1982 Relationships among ontogenetic, static, and evolutionary allometry. Am. J. Phys. Anthropol. 59, 139-149. (doi: 10. 1002/ajpa. 1330590204).
153. Simpson GG. 1944 Tempo and mode in evolution. New York, NY: Columbia University Press.
154. Rensch B. 1959 Evolution above the species level. New York, NY: Columbia University Press.
155. Zelditch ML, Carmichael AC. 1989 Ontogenetic variation in patterns of developmental and functional integration in skulls of Sigmodon fulviventer. Evolution 43, 814-824. (doi: 10. 2307/2409309).
156. Bolstad GH, Hansen TF, Pélabon C, Falahati-Anbaran M, Pérez-Barrales R, Armbruster WS. 2014 Genetic constraints predict evolutionary divergence in Dalechampia blossoms. Phil. Trans. R. Soc. B 369, 20130255. (doi: 10. 1098/rstb. 2013. 0255).
157. Klingenberg CP, Duttke S, Whelan S, Kim M. 2012 Developmental plasticity, morphological variation and evolvability: a multilevel analysis of morphometric integration in the shape of compound leaves. J. Evol. Biol. 25, 115-129. (doi: 10. 1111/j. 1420-9101. 2011. 02410. x).
158. Houle D, Pélabon C, Wagner GP, Hansen TF. 2011 Measurement and meaning in biology. Q. Rev. Biol. 86, 3-34. (doi: 10. 1086/658408).
159. Van Valen L. 1974 Multivariate structural statistics in natural history. J. Theor. Biol. 45, 235-247. (doi: 10. 1016/0022-5193(74)90053-8).
160. Cane WP. 1993 The ontogeny of postcranial integration in the common tern, Sterna hirundo. Evolution 47, 1138-1151. (doi: 10. 2307/2409980).
161. Cheverud JM, Rutledge JJ, Atchley WR. 1983 Quantitative genetics of development: genetic correlations among age-specific trait values and the evolution of ontogeny. Evolution 37, 895-905. (doi: 10. 2307/2408405).
162. Wagner GP. 1984 On the eigenvalue distribution of genetic and phenotypic dispersion matrices: evidence for a nonrandom organization of quantitative character variation. J. Math. Biol. 21, 77-95. (doi: 10. 1007/BF00275224).
163. Cheverud JM, Wagner GP, Dow MM. 1989 Methods for the comparative analysis of variation patterns. Syst. Zool. 38, 201-213. (doi: 10. 2307/2992282).
164. Pavlicev M, Cheverud JM, Wagner GP. 2009 Measuring morphological integration using eigenvalue variance. Evol. Biol. 36, 157-170. (doi: 10. 1007/s11692-008-9042-7).
165. Young NM. 2006 Function, ontogeny and canalization of shape variance in the primate scapula. J. Anat. 209, 623-636. (doi: 10. 1111/j. 1469-7580. 2006. 00639. x).
166. Willmore KE, Leamy L, Hallgrímsson B. 2006 Effects of developmental and functional interactions on mouse cranial variability through late ontogeny. Evol. Dev. 8, 550-657. (doi: 10. 1111/j. 1525-142X. 2006. 00127. x).
167. Shirai LT, Marroig G. 2010 Skull modularity in neotropical marsupials and monkeys: size variation and evolutionary constraint and flexibility. J. Exp. Zool. B 314, 663-683. (doi: 10. 1002/jez. b. 21367).
168. Kirkpatrick M. 2009 Patterns of quantitative genetic variation in multiple dimensions. Genetica 136, 271-284. (doi: 10. 1007/s10709-008-9302-6).
169. Hansen TF, Houle D. 2008 Measuring and comparing evolvability and constraint in multivariate characters. J. Evol. Biol. 21, 1201-1219. (doi: 10. 1111/j. 1420-9101. 2008. 01573. x).
170. Haber A. 2011 A comparative analysis of integration indices. Evol. Biol. 38, 476-488. (doi: 10. 1007/s11692-011-9137-4).
171. Hansen TF, Voje KL. 2011 Deviation from the line of least resistance does not exclude genetic constraints: a comment on Berner et al. (2010). Evolution 65, 1821-1822. (doi: 10. 1111/j. 1558-5646. 2011. 01281. x).
172. Agrawal AF, Stinchcombe JR. 2009 How much do genetic covariances alter the rate of adaptation. Proc. R. Soc. B 276, 1183-1191. (doi: 10. 1098/rspb. 2008. 1671).
173. Magwene PM. 2001 New tools for studying integration and modularity. Evolution 55, 1734-1745. (doi: 10. 1111/j. 0014-3820. 2001. tb00823. x).
174. Magwene PM. 2008 Using correlation proximity graphs to study phenotypic integration. Evol. Biol. 35, 191-198. (doi: 10. 1007/s11692-008-9030-y).
175. McGuigan K, Blows MW. 2010 Evolvability of individual traits in a multivariate context: partitioning the additive genetic variance into common and specific components. Evolution 64, 1899-1911.
176. Magwene PM. 2009 Statistical methods for studying modularity: a reply to Mitteroecker and Bookstein. Syst. Biol. 58, 146-149. (doi: 10. 1093/sysbio/syp007).
177. Albertson CR, Streelman JT, Kocher TD, Yelick PC. 2005 Integration and evolution of the cichlid mandible: the molecular basis of alternate feeding strategies. Proc. Natl Acad. Sci. USA 102, 16287-16292. (doi: 10. 1073/pnas. 0506649102).
178. Juenger T, Perez-Perez JM, Bernal S, Micol JL. 2005 Quantitative trait loci mapping of floral and leaf morphology traits in Arabidopsis thaliana: evidence for modular genetic architecture. Evol. Dev. 7, 259-271. (doi: 10. 1111/j. 1525-142X. 2005. 05028. x).
179. Hall MC, Basten CJ, Willis JH. 2006 Pleiotropic quantitative trait loci contribute to population divergence in traits associated with life-history variation in Mimulus guttatus. Genetics 172, 1829-1844. (doi: 10. 1534/genetics. 105. 051227).
180. Parsons KJ, Márquez E, Albertson RC. 2012 Constraint and opportunity: the genetic basis and evolution of modularity in the cichlid mandible. Am. Nat. 178, 64-78. (doi: 10. 1086/663200).
181. Hermisson J, McGregor AP. 2008 Pleiotropic scaling and QTL data. Nature 456, E3. (doi: 10. 1038/nature07452).
182. Wagner GP, Kenney-Hunt JP, Pavlicev M, Peck JR, Waxman D, Cheverud JM. 2008 Pleiotropic scaling of gene effects and the 'cost of complexity'. Nature 452, 470-473. (doi: 10. 1038/nature06756).
183. Pavlicev M, Wagner GP, Noonan JP, Hallgrimsson B, Cheverud JM. 2013 Genomic correlates of relationship QTL involved in fore-versus hind-limb divergence in mice. Genome Biol. Evol. 5, 1926-1936. (doi: 10. 1093/gbe/evt144).
184. Göring HHH, Terwilliger JD, Blangero J. 2001 Large upward bias in estimation of locus-specific effects from genomewide scans. Am. J. Hum. Genet. 69, 1357-1369. (doi: 10. 1086/324471).
185. Yi N, George V, Allison DB. 2003 Stochastic search variable selection for identifying quantitative trait loci. Genetics 164, 1129-1138.
186. Xu S. 2007 An empirical Bayes method for estimating epistatic effects of quantitative trait loci. Biometrics 63, 513-521. (doi: 10. 1111/j. 1541-0420. 2006. 00711. x).
187. Faye LL, Sun L, Dimitromanolakis A, Bull SB. 2011 A flexible genome-wide boot-strap method that accounts for ranking and threshold-selection bias in GWAS interpretation and replication study design. Stat. Med. 30, 1898-1912. (doi: 10. 1002/sim. 4228).
188. Bacanu S-A, Kendler KS. 2012 Extracting actionable information from genome scans. Genet. Epidemiol. 37, 48-59. (doi: 10. 1002/gepi. 21682).
189. Zhang J, Yue C, Zhang Y-M. 2012 Bias correction for estimated QTL effects using the penalized maximum likelihood method. Heredity 108, 396-402. (doi: 10. 1038/hdy. 2011. 86).
190. Wagner GP. 1989 The origin of morphological characters and the biological basis of homology. Evolution 43, 1157-1171. (doi: 10. 2307/2409354).
191. Wagner GP. 2014 Homology, genes, and evolutionary innovation. Princeton, NJ: Princeton University Press.
192. Wagner GP, Schwenk K. 2000 Evolutionarily stable configurations: functional integration and the evolution of phenotypic stability. Evol. Biol. 31, 155-217.
193. Mosimann JE. 1970 Size allometry: size and shape variables with characterizations of the lognormal and generalized gamma distributions. J. Am. Stat. Assoc. 65, 930-945. (doi: 10. 1080/01621459. 1970. 10481136).
194. Hansen TF, Pelabon C, Armbruster WS. 2007 Comparing variational properties of homologous floral and vegetative characters in Dalechampia scandens: testing the Berg hypothesis. Evol. Biol. 34, 86-98. (doi: 10. 1007/s11692-007-9006-3).
195. Fornoni J, Ordano M, Boege K, Dominguez CA. 2009 Phenotypic integration: between zero and how much is too much. New Phytol. 183, 248-250. (doi: 10. 1111/j. 1469-8137. 2009. 02911. x).
196. Harder LD. 2009 Questions about floral (dis)integration. New Phytol. 183, 247-248. (doi: 10. 1111/j. 1469-8137. 2009. 02881. x).
197. Boduriansky R, Day T. 2003 The evolution of static allometry in sexually selected traits. Evolution 57, 2450-2458. (doi: 10. 1111/j. 0014-3820. 2003. tb01490. x).
198. Schmidt-Nielsen K. 1984 Scaling: why is animal size so important? London, UK: Cambridge University Press.
199. Savageau MA. 1979 Allometric morphogenesis of complex systems: derivation of the basic equations from first principles. Proc. Natl Acad. Sci. USA 76, 6023-6025. (doi: 10. 1073/pnas. 76. 12. 6023).
200. Ushimaru A, Nakata K. 2001 Evolution of flower allometry and its significance for pollination success in the deceptive orchid Pogonia japonica. Int. J. Plant Sci. 162, 1307-1311. (doi: 10. 1086/322944).
201. Eberhard WG, Huber BA, Rodriguez RL, Briceno RD, Salas I, Rodriquez V. 1998 One size fits all? Relationships between the size and degree of variation in genitalia and other body parts in twenty species of insects and spiders. Evolution 52, 415-431. (doi: 10. 2307/2411078).
202. Kodric-Brown A, Sibly RM, Brown JH. 2006 The allometry of ornaments and weapons. Proc. Natl Acad. Sci. USA 103, 8733-8738. (doi: 10. 1073/pnas. 0602994103).
203. Pérez-Barrales R, Simón-Porcar VI, Santos-Gally R, Arroyo J. 2014 Phenotypic integration in style dimorphic daffodils (Narcissus, Amaryllidaceae) with different pollinators. Phil. Trans. R. Soc. B 369, 20130258. (doi: 10. 1098/rstb. 2013. 0258).
204. Ellis AG, Brockington SF, de Jager ML, Mellers G, Walker RH, Glover BJ. 2014 Floral trait variation and integration as a function of sexual deception in Gorteria diffusa. Phil. Trans. R. Soc. B 369, 20130563. (doi: 10. 1098/rstb. 2013. 0563).
205. Gómez JM, Perfectti F, Klingenberg CP. 2014 The role of pollinator diversity in the evolution of corolla-shape integration in a pollination-generalist plant clade. Phil. Trans. R. Soc. B 369, 20130257. (doi: 10. 1098/rstb. 2013. 0257).
206. Stock AJ, Campitelli BE, Stinchcombe JR. 2014 Quantitative genetic variance and multivariate clines in the Ivyleaf morning glory, Ipomoea hederacea. Phil. Trans. R. Soc. B 369, 20130259. (doi: 10. 1098/rstb. 2013. 0259).
207. Pitchers W, Wolf JB, Tregenza T, Hunt J, Dworkin I. 2014 Evolutionary rates for multivariate traits: the role of selection and genetic variation. Phil. Trans. R. Soc. B 369, 20130252. (doi: 10. 1098/rstb. 2013. 0252).