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Biased Polyphenism in Polydactylous Cats Carrying a Single Point Mutation: The Hemingway Model for Digit Novelty

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Abstract

Point mutations in a cis-regulatory element of Sonic Hedgehog are frequently associated with preaxial polydactyly in humans, mice, and cats. The Hemingway mutant in the Maine Coon cat exhibits polyphenic effects of polydactyly that are not equally distributed. A statistical analysis of a comprehensive data base of Hemingway mutants reveals a biased and discontinuous distribution of extra digits. Further biases exist in the difference of effects in fore- versus hind-limbs and in left–right asymmetry. These non-equally distributed phenotypic effects cannot be explained by the point mutation alone. We propose a double mapping model, termed the Hemingway Model, to account for the biased distribution of supernumerary digits. The model is based on the random bistability of individual cells in the limb area affected by the mutation and on the application of the Central Limit Theorem. It proposes two kinds of mapping events that (a) transform a mutational effect of single additive changes into a continuous distribution, and (b) transform the continuous distribution into discrete character states via developmental threshold effects. The threshold widths for the occurrence of discrete extra digits are specified as units of standard deviations of the continuous variable. This makes it possible to specify the generation of empirical developmental variables (the liability of quantitative genetics) as a result of developmental parameters that give rise to biased morphological patterns and phenotypic novelty.

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References

  • Adams, W. J. (2009). The life and times of the central limit theorem, Vol. 35. American Mathematical Society. History of Mathematics.

  • Alber, M., Glimm, T., Hentschel, H. E., Kazmierczak, B., Zhang, Y.-T., Zhu, J., et al. (2008). The morphostatic limit for a model of skeletal pattern formation in the vertebrate limb. Bulletin of Mathematical Biology, 79(2), 460–483.

    Article  Google Scholar 

  • Albuisson, J., Isidor, B., Giraud, M., Pichon, O., Marsaud, T., David, A., et al. (2011). Identification of two novel mutations in Shh long-range regulator associated with familial pre-axial polydactyly. Clinical Genetics, 79(4), 371–377.

    Article  CAS  PubMed  Google Scholar 

  • Babbs, C., Furniss, D., Morris-Kay, G. M., & Wilkie, A. O. M. (2008). Polydactyly in the mouse mutant Doublefoot involves altered Gli3 processing and is caused by a large deletion in cis to Indian hedgehog. Mechanisms of Development, 125(5–6), 517–526.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bénazet, J. D., & Zeller, R. (2009). Vertebrate limb development: Moving from classical morphogen gradients to an integrated 4-dimensional patterning system. Cold Spring Harbor Perspectives in Biology, 1(4), a001339. doi:10.1101/cshperspect.a001339.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bimonte, S., De Angelis, A., Quagliata, L., Giusti, F., Tammaro, R., Dallai, R., et al. (2011). Ofd1 is required in limb bud patterning and endrochondral bone development. Development Biology, 349(2), 179–191.

    Article  CAS  Google Scholar 

  • Cameron, D. A., Pennimpede, T., & Petkovitch, M. (2009). Tulp3 is a critical repressor of mouse hedgehog signaling. Developmental Dynamics, 238(5), 140–149.

    Article  Google Scholar 

  • Chakravarti, A., & Kapoor, A. (2012). The mendelian puzzles. Variation that lie outside of then coding region of a mutated gene can give rise to a range of clinical phenotypes for a Mendelian genetic disorder. Science, 335, 930–931.

    Article  CAS  PubMed  Google Scholar 

  • Chaturvedi, R., Huang, C., Kazmierczak, B., Schneider, R., Schneider, T., Izaguirre, J. A., et al. (2005). On multiscale approaches to three-dimensional modeling of morphogenesis. Journal of the Royal Society, Interface, 2(3), 237–253.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen, Y., Knezevi, V., Ervin, V., Hutson, R., Ward, Y., & Mackem, S. (2004). Direct interaction with Hoxd proteins reverses Gli3-repressor function to promote digit formation downstream of Shh. Development, 131(10), 2339–2347.

    Article  CAS  PubMed  Google Scholar 

  • Christley, S. (2008). Modeling and simulation of vertebrate limb development and algorithms for comparative genomics. Dissertation http://etd.nd.edu/ETD-db/theses/available/etd-04162008-120704/unrestricted/ChristleyS042008.pdf. Accessed October 01, 2012.

  • Cickowski, T., Huang, C., Chaturvedi, R., Gimm, T., Hentschel, H. G. E., Alber, M., et al. (2005). A Framework for three-dimensional simulation of morphogenesis. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2(4), 273–288.

    Article  Google Scholar 

  • Crampin, E. J., Gaffney, E. A., & Maini, P. K. (2002a). Mode-doubling and tripling in reaction–diffusion patterns on growing domains: A piecewise linear model. Journal of Mathematical Biology, 44(2), 107–128.

    Article  CAS  PubMed  Google Scholar 

  • Crampin, J. E., Hackborn, W. W., & Maini, P. K. (2002b). Pattern formation in reaction–diffusion models with nonuniform domain growth. Bulletin of Mathematical Biology, 64(4), 747–769.

    Article  CAS  PubMed  Google Scholar 

  • Dahte, K. (2009). Molekulare Ursachen isolierter Handfehlbildungen am Beispiel des BMP-Signalwegs und von SHH. Habilitationsschrift. http://www.diss.fu-berlin.de/diss/servlets/MCRFileNodeServlet/FUDISS_derivate_000000008148/Habilitationsschrift_Dathe_final.pdf?hosts=.

  • Danforth, C. H. (1947a). Heredity of polydactyly in the cat. The Journal of Heredity, 38(4), 107–112.

    CAS  PubMed  Google Scholar 

  • Danforth, C. H. (1947b). Morphology of the feet in polydactyl cats. The American Journal of Anatomy, 80(2), 143–171.

    Article  CAS  PubMed  Google Scholar 

  • Dillon, R., Cadgil, C., & Othmer, H. G. (2003). Short- and long-range effects of Sonic hedgehog in limb development. Proceedings of the National Academy of the Sciences of the United States of America, 100(18), 10152–10157.

    Article  CAS  Google Scholar 

  • Driess, S. J. (2005). Punktmutationsanalysen bei GLI3-assoziierten Krankheitsbildern: Greig Cephalopolysyndaktylie-Syndrom, Pallister-Hall-Syndrom und isolierte Polydaktylien. Dissertation, University of Marburg.

  • Dunn, I. C., Paton, I. R., Clelland, A. K., Sebastian, S., Johnson, E. J., McTeir, L., et al. (2011). The chicken polydacyty (Po) causes allelic imbalance and ectopic expression of Shh during limb development. Development Dynamics, 240(5), 1163–1172.

    Article  CAS  Google Scholar 

  • Falconer, D. S. (1989). Introduction to quantitative genetics. New York: Longman Scientific & Technical.

    Google Scholar 

  • Farooq, M., Troelsen, J. E., Boyd, M., Eiberg, H., Hansen, L., Hussain, M. S., et al. (2010). Preaxial polydactylous/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long range cis-regulator element ZRS. European Journal of Human Genetics, 18(6), 733–736.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fischer, H. (2011). A History of the central limit theorem. From classical to modern probability theory. New York: Springer.

    Google Scholar 

  • Fromental-Ramain, C., Warot, X., Messadecq, N., LeMeur, M., Dollé, P., & Chambon, P. (1996). Hoxa-13 and Hoxd13 play a crucial role in the patterning of the limb autopod. Development, 122(10), 2997–3011.

    CAS  PubMed  Google Scholar 

  • Galis, F., van Alphen, J. J. M., & Metz, J. A. J. (2001). Why five fingers? Evolutionary constraints on digit numbers. Trends in Ecology & Evolution, 16(11), 637–646.

    Article  Google Scholar 

  • Gu, X. (2004). Statistical framework for a phylogenomic analysis of gene family expression profiles. Genetics, 167, 531.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hamelin, A. (2011). La Polydactylousie du Maine Coon. École Nationale Vétérinaire d’Alfort. Dissertation http://theses.vet-alfort.fr/telecharger.php?id=1334. Accessed October 01, 2012.

  • Haycraft, C. J., Zhang, Q., Song, B., Jackson, W. S., Detloff, P. J., Serra, R., et al. (2007). Intraflagellar transport is essential for endrochondral bone formation. Development, 134(2), 307–316.

    Article  CAS  PubMed  Google Scholar 

  • Hentschel, H. G., Glimm, T., Glazier, J. A., & Newman, S. A. (2004). Dynamical mechanisms for skeletal pattern formation in the vertebrate limb. Poceedings of the Royal Society Biologial Sciences, 271(1549), 1713–1722.

    Article  CAS  Google Scholar 

  • Honig, L., & Summerbell, D. (1985). Maps of strength of positional signalling activity in the developing chick wing bud. Journal of Embryology and Experimental Morphology, 87, 163–174.

    CAS  PubMed  Google Scholar 

  • Kirschner, Marc W., & Gerhart, John C. (2010). Facilitated variation. In M. Pigliucci & G. B. Müller (Eds.), Evolution—The extended synthesis (pp. 253–280). Boston: MIT Press.

    Chapter  Google Scholar 

  • Klopocki, E., Ott, C.-E., Benatar, N., Ullmann, R., Mundlos, S., & Lehmann, K. (2008). A microduplication of the long range SHH limb regulator (ZRS) is associated with triphalangeal thumb-polysyndactyly syndrome. Journal of Medical Genetics, 45(6), 370–375.

    Article  CAS  PubMed  Google Scholar 

  • Krawchuk, D., Weiner, S. J., Chen, Y.-T., Lu, B. C., Costantini, F., Behringer, R. R., et al. (2010). Twist 1 activity thresholds define multiple functions in limb development. Developmental Biology, 347(1), 133–146.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kuss, P., Villavicencio-Lorini, P., Witte, F., Klose, J., Albrecht, A. N., Seemann, P., et al. (2009). Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retonic acid synthesis. The Journal of Clinical Investigation, 119(1), 146–156.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lai, K., Robertson, M. J., & Schaffer, D. V. (2004). The sonic hedgehog signaling system as a bistable genetic switch. Biophysical Journal, 88(5), 2748–2757.

    Article  Google Scholar 

  • Lettice, L. A., Haeney, S. J. H., Purdie, L. A., Li, L., de Beer, P., Oostra, B. A., et al. (2003). Long range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Human Molecular Genetics, 12(14), 1725–1735.

    Article  CAS  PubMed  Google Scholar 

  • Lettice, L. A., Hill, A. E., Devenney, P. S., & Hill, R. E. (2008). Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Human Molecular Genetics, 17(7), 978–985.

    Article  CAS  PubMed  Google Scholar 

  • Lettice, L. A., Williamson, I., Wiltshire, J. H., Peluso, S., Devenney, P. S., Hill, A. E., et al. (2012). Opposing functions of the ETS factor family define Shh spatial expression in limb buds and underlie polydactyly. Developmental Cell, 22(2), 459–467.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li, J. (2011). The evolutionary implication of gene expression variation in eukaryotes: From yeast to human. Dissertation, University of Toronto.

  • Litingtung, Y., Dahn, R. D., Li, Y., Fallon, J. F., & Chiang, C. (2002). Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity. Nature, 418, 979–983.

    Article  CAS  PubMed  Google Scholar 

  • Madzvamuse, A., Gaffney, E. A., & Maini, P. K. (2010). Stability analysis of non-autonomous reaction-diffusion systems: The effects of growing domains. Journal of Mathematical Biology, 61(1), 133–164.

    Article  PubMed  Google Scholar 

  • McFadden, D. G., MCanally, J., Richardson, J. A., Charité, J., & Olson, E. L. (2002). Misexpression of dHAND induces ectopic digits in the developing limb bud in the absence of direct DNA binding. Development, 129(13), 3077–3088.

    CAS  PubMed  Google Scholar 

  • McGlinn, A., & Tabin, C. J. (2006). Mechanstic insight into how Shh patterns the vertebrate limb. Current Opinion in the Genetics & Development, 16(4), 426–432.

    Article  CAS  Google Scholar 

  • Meinhardt, H., & Gierer, A. (2000). Pattern formation by local self-activation and lateral inhibition. BioEssays, 22(8), 753–760.

    Article  CAS  PubMed  Google Scholar 

  • Miura, T., Shiota, K., Morris-Kay, G., & Maini, P. K. (2006). Mixed-mode pattern in Doublefoot mutant mouse limb—Turing reaction diffusion model on a growing domain during limb development. Journal of Theoretical Biology, 240, 562–573.

    Article  PubMed  Google Scholar 

  • Müller, G. B. (2010). Epigenetic innovation. In M. Pigliucci & G. B. Müller (Eds.), Evolution—The extended synthesis (pp. 307–332). Cambridge: MIT Press.

    Chapter  Google Scholar 

  • Newman, S. A., & Bhat, R. (2007). Activator-inhibitor dynamics of vertebrate limb pattern formation. Birth Defects Research C, 81(4), 305–319.

    Article  CAS  Google Scholar 

  • Newman, S. A., Christley, S., Glimm, T., Hentschel, H. G. E., Kazmierczak, B., Zhang, Y.-T., et al. (2008). Multiscale models for vertebrate limb development. Current Topics in Developmental Biology, 81, 311–340.

    Article  PubMed  Google Scholar 

  • Newman, S. A., & Müller, G. B. (2005). Origination and innovation in the vertebrate limb sekeleton: An epigenetic perspective. Journal of Experimental Zoology (Mol Dev Evol), 304(6), 593–609.

    Article  Google Scholar 

  • Nijhout, H. F. (2004). Stochastic gene expression: Dominance, thresholds and boundaries. In R. A. Veitia (Ed.), The biology of genetic dominance. Austin: Landes Bioscience.

    Google Scholar 

  • Nissim, S., Allard, P., Bandyopadhyay, A., Harfe, B. D., & Tabin, C. J. (2007). Characterization of novel ectordermal signaling center regulating Tbx2 and Shh in the vertebrate limb. Developmental Biology, 304(1), 9–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Niswander, L. (2003). Pattern formation: Old models out in a limb. Nature Reviews Genetics, 4(2), 133–143.

    Article  CAS  PubMed  Google Scholar 

  • Park, K., Kang, J., Subedi, K., Ha, J.-H., & Park, C. (2008). Canine polydactylous mutations with heterogeneous origin in the conserved intronic sequence of LMBR1. Genetics, 179(4), 2163–2172.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Patterson, V. L., Damrau, C., Paudyal, A., Reeve, B., Grimes, D. T., Stewart, M. E., et al. (2009). Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: Identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway. Human Molecular Genetics, 18(19), 1719–1739.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Peterson, T., & Müller, G. B. (2013). What is evolutionary novelty? Process versus character based definitions. Journal of Experimental Zoology (Molecular and Developmental Evolution), 320(6), 345–350.

    Article  Google Scholar 

  • Pigliucci, M., & Müller, G. B. (Eds.). (2010). Evolution—The extended synthesis. Cambridge: MIT Press.

  • Platt, K. A., Michaud, J., & Joyner, A. L. (1997). Expression of the mouse Gli and Ptc genes is adjacent to embryonic sources of hedgehog signals suggesting a conservation of pathways between flies and mice. Mechanisms of Development, 62, 121–135.

    Article  CAS  PubMed  Google Scholar 

  • Raj, A., & van Oudenaarden, A. (2008). Nature, nurture or chance: Stochastic gene expression and its consequences. Cell, 135(2), 216–226.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Saunders, J. W., & Gasseling, M. T. (1968). Ectodermal-mesenchymal interactions in the origin of limb symmetry. In R. E. Fleischmajer & R. Billingham (Eds.), Epithelial-mesenchymal interactions (pp. 78–97). Baltimore: Lippincott Williams & Wilkins.

    Google Scholar 

  • Semerci, C. N., Demirkan, F., Özdemir, M., Biskin, E., Akin, B., Bagci, H., et al. (2009). Homozygous feature of isolated triphalangeal thumb—Preaxial polydactyly linked to 7q36: No phenotypic difference between homozygotes and heterozygotes. Clinical Genetics, 76(1), 85–90.

    Article  CAS  PubMed  Google Scholar 

  • Shapiro, M. D., Bell, M. A., & Kingsley, D. M. (2006). Parallel genetic origins of pelvic reduction in vertebrates. Proceedings of the National Academy of Sciences, 103, 3753–13758.

    Google Scholar 

  • Sheth, R., Bastida, M. F., & Ros, M. (2007). Hoxd13 and Gli3 interactions modulate digit number in the amniote limb. Development Biology, 310(2), 430–441.

    Article  CAS  Google Scholar 

  • Sheth, R., Marcon, L., Bastida, M. F., Junco, M., Quintana, L., Dahn, R., et al. (2012). Hox genes regulate digit patterning by controlling the wavelength of a Turing-type mechanism. Science, 338, 1476–1480.

    Article  CAS  PubMed  Google Scholar 

  • Smith, J. C., & Wolpert, L. (1981). Pattern formation along the anteposterior axis of the chick wing: The increase in width following a polarizing region graft and the effect of X-irradiation. Journal of Embryology and Experimental Morphology, 63, 127–144.

    CAS  PubMed  Google Scholar 

  • Tabin, C. J. (1992). Why we have (only) five fingers per hand: Hox genes and the evolution of paired limbs. Development, 116, 289–296.

    CAS  PubMed  Google Scholar 

  • Talamillo, A., Bastida, M. F., Fernandez-Teran, M., & Ros, M. A. (2005). The development of the limb and the control of the number of digits. Clinical Genetics, 67, 143–153.

    Article  CAS  PubMed  Google Scholar 

  • Tickle, C. (1981). The number of polarizing region cells required to specify additional digits in the developing chick wing. Nature, 289, 295–298.

    Article  CAS  PubMed  Google Scholar 

  • Tickle, C. (2006). Making digit patterns in the vertebrate limb. Nature Reviews Molecular Cell Biology, 7, 45–53.

    Article  CAS  PubMed  Google Scholar 

  • Tickle, C., Summerbell, D., & Wolpert, L. (1975). Positional information and specification of digits in chicken limb morphogenesis. Nature, 254, 199–202.

    Article  CAS  PubMed  Google Scholar 

  • Turing, A. M. (1952). The chemical basis of morphogenesis. Philosophical Transactions of the Royal Society of London Series B, 237(641), 37–72.

    Article  Google Scholar 

  • Wagner, G. P., & Chiu, C. H. (2001). The tetrapod limb: A hypothesis on its origin. Journal of Experimental Zoology (Molecular and Developmental Evolution), 291(3), 226–240.

    Article  CAS  Google Scholar 

  • Wieczorek, D., Pawlik, B., Li, Y., Akarsu, N. A., Caliebe, N. A., May, K. J. W., et al. (2010). A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb. Human Mutation, 31(1), 81–89.

    Article  CAS  PubMed  Google Scholar 

  • Wilson, D. J., & Hinchliffe, J. R. (1987). The effect of zone polarizing activity (ZPA) on the anterior half of the chick wing bud. Development, 99(1), 99–108.

    CAS  PubMed  Google Scholar 

  • Wolpert, L. (1999). Vertebrate limb development and malformations. Pediatric Research, 46(3), 247–254.

    Article  CAS  PubMed  Google Scholar 

  • Wolpert, L. (2009). Diffusible gradients are out—An interview with Lewis Wolpert. Interviewed by Richardson, Michael K. The International Journal of Developmental Biology, 53(5–6), 659–662.

    PubMed  Google Scholar 

  • Wright, S. (1934a). An analysis of variability in number of digits in an inbred stain of guinea pigs. Genetics, 19(6), 506–536.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wright, S. (1934b). The result of crosses between inbred strains of guinea pigs, differing in number of digits. Genetics, 19(6), 537–551.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yada, Y., Makino, S., Chiqusa-Ishiwa, S., & Shiroishi, T. (2002). The mouse polydactylous mutation, luxate (lx), causes anterior shift of the anteposterior border in the developing hind limb bud. International Journal of Developmental Biology, 46(7), 975–982.

    CAS  PubMed  Google Scholar 

  • Yang, Y., Drossopoulou, G., Chuang, P.-T., Duprez, D., Marti, E., Bumcrot, D., et al. (1997). Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb. Development, 124(21), 4393–4404.

    CAS  PubMed  Google Scholar 

  • Zhang, Z., Sui, P., Dong, A., Hasssell, J., Cserjesi, P., Chen, Y.-T., et al. (2010). Preaxial polydactyly: Interactions among ETV, TWIST1 and Hand2 control anterior-posterior patterning of the limb. Development, 137(20), 3417–3426.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao, J., Ding, Y., Li, Y., Ren, K., Sha, J., Zhu, J., et al. (2009). HnRNP U mediates the long-range regulation of Shh expression during limb development. Human Molecular Genetics, 18(16), 3090–3097.

    Article  CAS  PubMed  Google Scholar 

  • Zhu, J., Zhang, Y.-T., Alber, M. S., & Newman, S. A. (2010). Bare bones patterning formation: A core regulatory network in varying geometrics reproduces major features of vertebrate limb development and evolution. PLoS ONE, 5(5), e10892. doi:10.1371/journal.pone.0010892.

    Article  PubMed Central  PubMed  Google Scholar 

  • Zuniga, A., Zeller, R., & Probst, S. (2012). The molecular basis of human congenital limb malformations. Wiley Interdisciplinary Reviews: Developmental Biology, 1(6), 803–822.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank the PolyTrak team, especially K. Bussard, USA, and V. Bode, Netherlands, for technical assistance with using PolyTrak. We also thank the experienced Maine Coon breeders, M. Roth and P. Nagl in Germany and S. Otten-Boult in the Netherlands, for their valuable support and patience in answering our questions. P. Shevtsova, a Maine Coon breeder in Moscow, provided the picture of the Hemingway mutant. The X-rays are reproduced with kind permission from S. Otten-Boult. We also express our thanks to two anonymous reviewers for their valuable comments and to Tim Peterson for help with the elements of style.

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  1. Department of Theoretical Biology, University of Vienna, Althanstraße 14, 1090, Vienna, Austria

    Axel Lange, Hans L. Nemeschkal & Gerd B. Müller

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  1. Axel Lange
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Correspondence to Gerd B. Müller.

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Lange, A., Nemeschkal, H.L. & Müller, G.B. Biased Polyphenism in Polydactylous Cats Carrying a Single Point Mutation: The Hemingway Model for Digit Novelty. Evol Biol 41, 262–275 (2014). https://doi.org/10.1007/s11692-013-9267-y

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