Additional information on specific projects is available below

NEW !!!


Check our NEW DATABASE (2015)


Check our new paper in BMC BIOLOGY (2013)


Check our new paper in Science (2013)


Check our paper in EvoDevo (2013)


Check here the new workhorses for studying the Evo-Devo of phenotypic novelties and convergences.


Check here our application system which attempts filling the gap between multi-species full genome comparisons and functional analysis.


Check here how MANTiS  allowed us (i) quantifying the Historical Constraints on Vertebrate Genome Evolution and (ii) demonstrating that low-quality genome sequences generate large problems in the study of genome evolution.


Check here our use of classical developmental and molecular genetics methods for understanding the molecular generative mechanisms of phenotypes of interest in multiple non-classsical mammalian and reptilian model species.


What is Evo-Devo?

    Molecular developmental biology and evolutionary molecular genetics have proven, these last 20 years, to be highly successful but, strangely enough, remained largely separated despite the obvious conceptual links between the two disciplines. Indeed, on one hand, molecular developmental biologists have focused on the use of a handful of model organisms (such as the nematode Caenorhabditis elegans, the fruitfly Drosophila melanogaster, the frog Xenopus tropicalis/laevis, and the laboratory mouse Mus musculus) for deciphering the fascinating processes by which cells differentiate, as well as tissues, organs, and organisms grow and develop. On the other hand, evolutionary molecular geneticists have investigated the modes and tempos of DNA and protein evolution in a multitude of organisms (from viruses to vertebrates), and developed the laboratory techniques and analytical methods allowing today to infer phylogenies, reconstruct population histories, uncover hidden biodiversity, and detect selection and stochastic patterns in laboratory and natural populations.

    Given that a large proportion of evolutionary mechanisms, namely, those pertaining to natural selection, act on the phenotypes that originate from development (i.e., genetic information and epigenetic parameters are translated into phenotypes during development), it was fully realized only in the 1990’s, that our understanding of both evolution and development would greatly benefit from the partial merging of the two above-mentioned disciplines into what is called today Evolutionary Developmental Biology (EVO-DEVO). This emerging approach has been recently recognized as a new and innovative discipline by the Academy of Sciences of the USA. The motivation of synthesizing findings from molecular developmental biology and evolutionary biology already yielded some spectacular results as, e.g., illustrated by the partial understanding of Hox gene involvement in the origin and evolution of characters, such as appendages and segmentation, across lineages. The existence of identical signals for the, supposedly independent, development of structures of similar functions (e.g., the eye) in very different lineages, has shaken concepts as central/major as homology. The significance of the new field of Evo-Devo is demonstrated by the recent establishment of specialized journals (e.g., Evolution & Development; JEZ-B: Molecular and Developmental Evolution; EvoDevo) and university chairs of evolutionary developmental biology are being established at an accelerated pace, especially in the US and the UK.

    The most important defining feature of Evo-Devo is that it explicitly addresses the generative mechanisms underlying the evolution of organismal forms on both short-term and long-term timescales. Uncovering these mechanisms will require the use of many additional model organisms. Evo-Devo studies are, by essence, highly multidisciplinary and integrative as they require investigation, across lineages, of morphological/ physiological, as well as of the underlying genomic, characters. Many recent and powerful concepts such as the self-organizational capabilities of cells and tissues, the dynamics of epigenetic interactions among developmental modules, the role of geometry and form in developmental and evolutionary processes (extending also into the field of theoretical biology), are pertinent for addressing the causal and reciprocal interrelations between development and evolution at multiple scales and multiple levels of analysis. Evo-Devo also requires diversity in the taxa analyzed, in the levels of analysis (from the gene – identification, expression, control - to the developmental mechanisms to the phenotype), and in the techniques used (the expression analysis and RNAi/morpholinos technologies from developmental genetics, and the genomic/analytical technologies from evolutionary genetics).

    We recently developed multiple non-classical model systems in vertebrates for Evo-Devo studies. Currently, our major interests are fourfold:

  1. (i)Developing new model species for EvoDevo,

  2. (ii)Uncovering the genetic basis of evolutionary novelties,

  3. (iii)Understanding phenotypic convergences,

  4. (iv)Identifying the role of physical mechanisms in EvoDevo.

(i) Non-classical model systems

The criteria that are relevant to the choice of a set of model species are multiple and can even be contradictory. We think that the only possibility is the use of a pragmatic (and partly subjective) optimisation approach, incorporating multiple criteria. We have applied such an approach for a set of species that could serve as the workhorses for evo-devo research within amniotes. We use these species in our laboratory for studying the Evo-Devo of phenotypic novelties and convergences, using classical developmental and molecular genetics methods (in-situ hybridization, DNA arrays, library building and sequencing, etc.).

Additional information is available HERE.

(ii) Lineage-specific novelties

Increase of complexity is certainly not a universal law of evolution. Indeed, multiple lineages, such as myzostomes and flatworms, probably exhibit derived (rather than ancestral), simplified body plans. Still, it is undisputable that some lineages in the phylogenetic tree of life are characterized by the accelerated acquisition of new and complex physiological and morphological characters. Some obvious examples include the origin of chromosomes, the origin of eukaryotes, the origin of sex, the origin of multicellularity, the origin of social groups, etc.  At a finer phylogenetic scale, examples of accelerated anagenesis can be found in vertebrates as well, especially at the origin of tetrapods, of mammals, and of birds. It is the accelerated rate of morphological/physiological evolution of the latter two lineages that explains the paraphyly of “reptiles” (exposed in basically every text book on evolution). Although the absolute amount of DNA in a haploid cell (the so called “c-value”) is very poorly correlated with organismal complexity, it is likely that at least some macroevolutionary events are due to the emergence of new genes or gene families. It is generally believed that some of the acquisitions of new genes (through duplications, retropositions, etc.) are correlated to at least some of the well-accepted major transitions of complexity in evolution. This project aims at identifying some of the gene acquisitions that are associated with evolutionary morphological and physiological transitions in selected internal branches of the vertebrate phylogenetic tree.

We approach this issue from two different avenues:

  1. Experimental identification of the molecular developmental generative mechanisms of lineage-specific phenotypes. Examples:

  2. Soon available (Sophie),

  3. Evolutionary comparative genomics, i.e., in-silico comparative analysis of full genomes in a phylogenetic framework (check for details HERE).

  4. Evolutionary comparative transcriptomics, i.e., in-silico comparative analysis of transcriptomes in a phylogenetic framework (check for details HERE)


(iii) Understanding phenotypic convergences

Soon available (Athanasia and Sophie)

(iv) Identifying the role of physical mechanisms in EvoDevo

To write !!


  1. Cracking the Code of Crocodile Scales

  2. Others (soon to come)

Selected publications

  1. Di-Poï N. & M. C. Milinkovitch
    The Anatomical Placode in Reptile Scale Morphogenesis Indicates Shared Ancestry
    Among Skin Appendages in Amniotes 
    Science Advances 2, e1600708 (2016) -   doi: 10.1126/sciadv.1600708

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  3. BulletSupporting movie

  4. Additional coverage

  5. Bulletcheck here

  6. Saenko S.V., Lamichhaney S., Martinez Barrio A., Rafati N.,
    Andersson L. & M. C. Milinkovitch
    Amelanism in the corn snake is associated with the insertion of an LTR-retrotransposon in the OCA2 gene 
    Scientific Reports 5, 17118 (2015)
  7. BulletOpen Access

  8. BulletDownload the Supplementary Materials file

  1. Tzika A.C., Ullate-Agote A., Grbic D. & M. C. Milinkovitch
    Reptilian Transcriptomes v2.0: An Extensive Resource for Sauropsida Genomics and Transcriptomics
    Genome Biol. Evol.  7: 1827-1841 (2015)

  2. BulletOpen Access

  3. BulletDownload the Supplementary Materials file

  4. BulletDatabase website: Reptilian-Transcriptomes v2.0

  1. Ullate-Agote A., Milinkovitch M.C. & A.C. Tzika
    The genome sequence of the corn snake (Pantherophis guttatus), a valuable resource
    for EvoDevo studies in squamates
    Int. J. Dev. Biol. 58: 881-888 (2014)

  2. BulletOpen Access

  3. BulletDownload the Cover

  1. Di-Poï N. & M.C. Milinkovitch
    Crocodylians Evolved Scattered Multi-Sensory Micro-Organs
    EvoDevo 2013, 4:19

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  3. Check Q&A in Biome: online highlights from BioMed Central journals

  4. Check coverage (TV programs, Websites, and News Papers) HERE

  5. Brykczynska U., Tzika A.C., Rodriguez I.,  & M. C. Milinkovitch
    Differential expansion of vomeronasal chemosensory receptors in snakes and mammals
    Genome Biology & Evolution (in press): doi: 10.1093/gbe/evt013

  6. BulletOpen Access

  7. BulletDownload the Supplementary Materials

  1. Milinkovitch M.C., Manukyan L., Debry A., Di-Poï N., Martin S., Singh D.,
    Lambert D., Zwicker M.
    Crocodile Head Scales Are Not Developmental Units But Emerge
    from Physical Cracking
    Science 339, 78 (2013) -- DOI: 10.1126/science.1226265

  2. BulletDownload a FREE reprint from our ‘Publications’ page

  3. BulletDownload the Supplementary Materials file

  4. BulletCheck the slideshow from Science (soon available)

  5. BulletCheck the PodCast from Science

  6. BulletCheck Sarah C. P. Williams’ article in ScienceNOW

  7. Coverage

  8. BulletCheck the slideshow from BBC Nature

  9. BulletCheck the Movie illustrating the Computer Graphics Tools (version 1)

  10. BulletCheck the Movie illustrating the Computer Graphics Tools (version 2)

  11. Check more coverage (TV programs, Websites, and News Papers) HERE

  12. Di-Poï N., Montoya-Burgos J.I., Miller H., Pourquié O., Milinkovitch M.C. & D. Duboule
    Changes in Hox genes’ structure and function during the evolution of the squamate body plan
    Nature, 464: 99-103 (2010)

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  1. Saenko S., Teyssier J., van der Marel D. & M. C. Milinkovitch
    Precise colocalization of interacting structural and pigmentary elements generates extensive color pattern variation in Phelsuma lizards
    BMC Biology 2013, 11: 105

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  1. Milinkovitch M.C., Helaers R., Depiereux E., Tzika A.C., & T. Gabaldon
    2X genomes - depth does matter
    Genome Biology, 11 (2): R16 (2010)
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  3. Milinkovitch M.C., Helaers R., & A.C. Tzika
    Historical Constraints on Vertebrate Genome Evolution
    Genome Biololgy & Evolution 2010: 13-18 (2010)

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  5. Tzika A. C. & M. C. Milinkovitch.
    A Pragmatic Approach for Selecting Evo-Devo Model Species in Amniotes
    Chapter 7 Pages 119-140 in ‘Evolving Pathways; Key Themes in Evolutionary Developmental Biology’ (A. Minelli & G. Fusco, eds.), Cambridge University Press 2008

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  7. Milinkovitch M.C. & A. C. Tzika
    Escaping the Mouse Trap; the Selection of New Evo-Devo Model Species
    Journal of Experimental Zoology (Mol. Dev. Evol.) 308B: 337–346 (2007)
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  9. BulletNews Coverage

  10. Bossuyt F. & M. C. Milinkovitch
    Convergent Adaptive Radiations in Madagascan and Asian Ranid Frogs
    Reveal Co-variation between Larval and Adult Traits.

    PNAS 97: 6585-6590 (2000)

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