Evolutionary novelties; Evolutionary convergences; Comparative genomics; Comparative transcriptomics; Evo-Devo; Spines; Syndactyly; New model organisms; convergence; molecular development; evo-evo; evolutionary novelty
Werneburg Ingmar, Tzika Athanasia C, Hautier Lionel, Asher Robert J, Milinkovitch Michel C, Sánchez-Villagra Marcelo R (2012), Development and embryonic staging in non-model organisms: the case of an afrotherian mammal., in Journal of anatomy
Tiedemann R, Paulus KB, Havenstein K, Thorstensen S, Petersen A, Lyngs P, Milinkovitch MC (2011), Alien eggs in duck nests: brood parasitism or a help from Grandma?, in MOLECULAR ECOLOGY
, 20(15), 3237-3250.
Li X, Liu YY, Tzika AC, Zhu Q, Van Doninck K, Milinkovitch MC (2011), Analysis of global and local population stratification of finless porpoises Neophocaena phocaenoides in Chinese waters, in MARINE BIOLOGY
, 158(8), 1791-1804.
Ciofi C, Tzika AC, Natali C, Watts PC, Sulandari S, Zein MSA, Milinkovitch MC (2011), Development of a multiplex PCR assay for fine-scale population genetic analysis of the Komodo monitor Varanus komodoensis based on 18 polymorphic microsatellite loci, in MOLECULAR ECOLOGY RESOURCES
, 11(3), 550-556.
Tzika Athanasia C, Helaers Raphaël, Schramm Gerrit, Milinkovitch Michel C (2011), Reptilian-transcriptome v1.0, a glimpse in the brain transcriptome of five divergent Sauropsida lineages and the phylogenetic position of turtles., in EvoDevo
, 2(1), 19-19.
Milinkovitch MC, Helaers R, Depiereux E, Tzika AC, Gabaldon T (2010), 2x genomes - depth does matter, in GENOME BIOLOGY
, 11(2), 1-12.
Di-Poi N, Montoya-Burgos JI, Miller H, Pourquie O, Milinkovitch MC, Duboule D (2010), Changes in Hox genes' structure and function during the evolution of the squamate body plan, in NATURE
, 464(7285), 99-103.
Milinkovitch MC, Helaers R, Tzika AC (2010), Historical Constraints on Vertebrate Genome Evolution, in GENOME BIOLOGY AND EVOLUTION
, 2, 13-18.
Milinkovitch Michel C, Helaers Raphaël, Tzika Athanasia C (2010), Historical constraints on vertebrate genome evolution., in Genome biology and evolution
, 2, 13-8.
Helaers R, Milinkovitch MC (2010), MetaPIGA v2.0: maximum likelihood large phylogeny estimation using the metapopulation genetic algorithm and other stochastic heuristics, in BMC BIOINFORMATICS
, 11, 1-11.
Tzika AC, D'Amico E, Alfaro-Shigueto J, Mangel JC, Van Waerebeek K, Milinkovitch MC (2010), Molecular identification of small cetacean samples from Peruvian fish markets, in CONSERVATION GENETICS
, 11(6), 2207-2218.
Ciofi C, Tzika AC, Natali C, Chelazzi G, Naziridis T, Milinkovitch MC (2009), Characterization of microsatellite loci in the European pond turtle Emys orbicularis, in MOLECULAR ECOLOGY RESOURCES
, 9(1), 189-191.
Rosa SFP, Monteyne D, Milinkovitch MC (2009), Development of 10 highly-polymorphic microsatellite markers in the vulnerable Galapagos land iguanas (genus Conolophus), in MOLECULAR ECOLOGY RESOURCES
, 9(1), 376-379.
Tzika AC, Remy C, Gibson R, Milinkovitch MC (2009), Molecular genetic analysis of a captive-breeding program: the vulnerable endemic Jamaican yellow boa, in CONSERVATION GENETICS
, 10(1), 69-77.
Van Doninck K, Mandigo ML, Hur JH, Wang P, Guglielmini J, Milinkovitch MC, Lane WS, Meselson M (2009), Phylogenomics of Unusual Histone H2A Variants in Bdelloid Rotifers, in PLOS GENETICS
, 5(3), 1-13.
As sad as this realization may be, we must accept that the community of experimental and theoretical evolutionists has learned very little about the mechanisms behind the astonishing macroevolutionary patterns we, and many others, have uncovered through molecular phylogeny inference. The key issue is to understand how morphology and physiology are altered to produce new forms serving novel functions. Clearly, major breakthroughs will require new approaches, including Evolutionary Developmental Biology (Evo-Devo), a discipline that explicitly addresses the generative mechanisms underlying the evolution of life forms. Uncovering these mechanisms will require a diversity in the taxa analyzed, in the levels of analysis, and in the techniques used. Here, we propose bottom-up (using innovative comparative genomics/transcriptomics/proteomics) and top-down (molecular embryology) approaches for investigating the molecular genetic basis of lineage-specific evolutionary novelties and phenotypic convergences, two patterns that phylogeneticists recurrently revealed in multiple lineages.?The first part of our project aims at identifying some of the gene/transcript/protein acquisitions that are associated with evolutionary morphological and physiological transitions in internal branches of the chordate phylogenetic tree, especially the origin of mammals and the origin of Archosauria. We will approach this issue from three different bottom-up avenues: (i) in-silico analysis of publicly-available full genomes in a phylogenetic and protein-interactome context, (ii) sequencing and comparisons of complete transcriptomes, and (iii) comparative proteomics. For an efficient in-silico comparison of genomes, we will continue developing our MANTiS software pipeline (Tzika et al. 2008) for identifying gene gains and losses on specific branches of the tree, genome content of ancestral species, statistically over- / under-represented molecular functions and biological processes, and tissue specificity of gained, duplicated, and lost genes. We will integrate new developments for exploring and interrogating animal high-coverage genome content and associated functional data within a protein interactome context (in collaboration with Pr. Marc Vidal, Harvard Medical School, USA). For an efficient comparison of full transcriptomes across species, we propose to use the recent revolutionary 454 technology of DNA sequencing in microfabricated high-density picolitre reactors for the ultra-fast sequencing of cerebral tissue full transcriptomes in multiple species and multiple developmental stages. Contrary to Sanger sequencing or the use of microarrays, this approach will combine the advantages of high-throughput and of sequence information, and will uncover evolutionary patterns of gene expression in addition to lineage-specific genes. Finally, we will complete the in-silico comparisons of full genomes and the sequencing of full transcriptomes by comparative proteomics experiments (in collaboration with Dr. Clive D’Santos, Bergen Norway). We will perform two-dimentional protein electrophoresis runs followed by Western blotting for the identification of lineage-specific proteins. Candidates will be extracted from electrophoresis gels and sequenced by mass spectrometry. We gathered highly-promising preliminary data for each of these three approaches.?The second part of our project aims at using top-down approaches for understanding the molecular mechanisms responsible for some of the many major convergences observed in multiple lineages. These last two years, we successfully set-up breeding colonies of non-classical model organisms (within mammals and reptiles) necessary for these studies. We chose to investigate here the convergent development of spines within eutherians and of syndactyly (i.e., fusion between two digits) in marsupials. We will study the molecular basis underlying the convergent conversion of hair follicles into spine-producing organs in the spiny mouse (Acomys dimidiatus), the African pygmy hedgehog (Atelerix albiventris), and the lesser hedgehog tenrec (Echinops telfairi). We will determine in the three species (a) the morphological characteristics of spines and their localization on the animal, (b) the expression of key placode regulators and placode size during spine development, and (c) the role of cell-cell signaling pathways in defining spine placode size, spacing and early morphogenesis in culture. Many genes responsible for abnormal syndactyly in mammals (including humans) are good candidates for the determinism of natural convergent syndactyly in two lineages of marsupials. With most of the stages of toe formation and separation occurring in the pouch, syndactylous marsupials will constitute an exceptional model for studying these mechanisms in details. We will use our original and newly-developed marsupial model, the sugar glider (Petaurus breviceps), for studying the generating mechanisms of syndactyly through in-situ hybridizations at multiple developmental stages and DNA sequencing of candidate genes in multiple species.