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

  title={Biased Polyphenism in Polydactylous Cats Carrying a Single Point Mutation: The Hemingway Model for Digit Novelty},
  author={Axel Lange and Hans L. Nemeschkal and Gerd B. M{\"u}ller},
  journal={Evolutionary Biology},
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… 

Crowdfunded whole-genome sequencing of the celebrity cat Lil BUB identifies causal mutations for her osteopetrosis and polydactyly

The genome of Lil BUB, a celebrity cat affected by rare disease phenotypes characterized by supernumerary digits, osteopetrosis and dwarfism, is sequenceed, highlighting the importance of genomic analysis in the identification of disease-causing mutations and support crowdfunding as a means to fund low-budget projects and as a platform for scientific communication.

Deep Homology?: Uncanny Similarities of Humans and Flies Uncovered by Evo-Devo

Deep Homology?: Uncanny Similarities of Humans and Flies Uncovered by Evo-Devo is Lewis Held's final act in a threepart series discussing developmental evolution. Part one of the series−Quirks of

Specialize or risk disappearance – empirical evidence of anisomerism based on comparative and developmental studies of gnathostome head and limb musculature

Comparisons and review of the literature indicate that there is also a trend towards anisomerism during development, thus providing a further example of a parallel between ontogeny and phylogeny, and will inform future discussions on modularity, complexity, body plans, phenotypic integration and macroevolution.

Evidence for an amphibian sixth digit

It is proposed here that the prehallux seen in various species of amphibians generally represents a rudimentary sixth digit, as is evident from anatomical features, development, and molecular marker expression.

Evolutionary biology today and the call for an extended synthesis

The proposition that phenotypic plasticity may engender new adaptive phenotypes that are later genetically assimilated or accommodated is theoretically plausible; it may be most likely when the new phenotype is not truly novel, but is instead a slight extension of a reaction norm already shaped by natural selection in similar environments.

Phenotypic Novelty in EvoDevo: The Distinction Between Continuous and Discontinuous Variation and Its Importance in Evolutionary Theory

It is argued that an EvoDevo-based approach to novelty is inherently mechanistic, treats the phenotype as an agent with generative potential, and prompts a distinction between continuous and discontinuous variation in evolutionary theory.

Form and function remixed: developmental physiology in the evolution of vertebrate body plans

  • S. Newman
  • Biology
    The Journal of physiology
  • 2014
This paper discusses three examples of morphological motifs of vertebrate bodies and organs, the somites, the skeletons of the paired limbs, and musculoskeletal novelties distinctive to birds, for which evolutionary origination and transformation can be understood on the basis of the physiological and biophysical determinants of their development.

Post-genomics, Evo-Devo and the recurrence of teleologic thought

A re-examination of Driesch’s drive to wholeness appears timely, while his teleologic postulates remain undecidable by reductionist reasoning.

Why an extended evolutionary synthesis is necessary

A renewed and extended theoretical synthesis is advocated, advocated by several authors in this issue, which overcomes many of the limitations of traditional gene-centric explanation and entails a revised understanding of the role of natural selection in the evolutionary process.

Integrating Parasites and Pathogens into the Study of Geographic Range Limits

Recently, parasites have been used to infer population demographic and ecological information about their host organisms and it is concluded that this strategy can be further exploited to understand geographic range limitations of both host and parasite populations.



Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly.

The polydactyly mutations define a new genetic mechanism that results in human congenital abnormalities and identifies a pathogenetic mechanism that may underlie other congenital diseases.

Canine Polydactyl Mutations With Heterogeneous Origin in the Conserved Intronic Sequence of LMBR1

Unlike the previously characterized cases of PPD identified in the mouse and human ZRS regions, the canine mutations in pZRS lacked the ectopic expression of sonic hedgehog in the anterior limb bud, distinguishing its role in limb development from that of the ZRS.

Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retinoic acid synthesis.

It is proposed that mutated Hoxd13 causes polydactyly in SPD by inducing extraneous interdigital chondrogenesis, both directly and indirectly, via a reduction in RA levels.

The chicken polydactyly (Po) locus causes allelic imbalance and ectopic expression of Shh during limb development

  • I. DunnI. Paton M. Davey
  • Biology
    Developmental dynamics : an official publication of the American Association of Anatomists
  • 2011
Using polymorphisms in the chicken Shh sequence, it is confirmed that the ZRS region directly regulates Shh expression in the developing limb causing ectopic Shh Expression in the anterior leg, prolonged Shhexpression in the posterior limb, and allelic imbalance between wt and Slk Shh alleles in heterozygote limbs.

Preaxial polydactyly/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long-range cis-regulatory element ZRS

Electrophoretical mobility shift assay demonstrated a marked difference between wild-type and the mutant probe, which uniquely bound one or several transcription factors extracted from Caco-2 cells, supporting a model in which ectopic anterior SHH expression in the developing limb results from abnormal binding of one or more transcription factors to the mutant sequence.

Homozygous feature of isolated triphalangeal thumb–preaxial polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotes

A novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene is identified, identified as the first homozygote case of the triphalangeal thumb‐preaxial polydactyly phenotype.

Hox Genes Regulate Digit Patterning by Controlling the Wavelength of a Turing-Type Mechanism

Mouse genetics and computer modeling are used to argue for a Turing-type mechanism underlying digit patterning, in which the dose of distal Hox genes modulates the digit period or wavelength.

Mendelian Puzzles

It is demonstrated that a disorder called Joubert syndrome is caused by mutations in either of two different, adjacent genes that share a common regulatory region (constituting a so-called cisregulatory module), one example of how human genetics is maturing from a focus on single genes into a more genomic view.

A microduplication of the long range SHH limb regulator (ZRS) is associated with triphalangeal thumb-polysyndactyly syndrome

A novel microduplication in 7q36.3 results in a similar TPT-PS phenotype as caused by single nucleotide alterations in the ZRS, the limb specific SHH regulatory element, the growing list of mechanisms that cause abnormalities of long range transcriptional control.