Team 15: Evolutionary Epigenomics and Genetic Conflicts

Access to genetic information is organized by epigenetic modifications and chromatin pathways. These mechanisms predate the last common ancestor to all eukaryotes and are hypothesized to perform conserved functions. Nevertheless, we find that they are subject to diversification in mammals (see publications). Genetic conflicts are well known to drive genome diversification, however their impact on epigenome evolution is poorly understood. Our team uses phylogenetics to identify chromatin pathways with evolutionary signatures of genetic conflicts, and test their function on the epigenome in vivo.


Recherche soutenue par: FRM Amorçage de Jeunes Équipes (AJE201912009932) 2020-2022; ANR Jeune Chercheur/Chercheuse (SHAMAN) 2023-2027; ANR Partner (MomDad) 2022-2025.


Currently, we use mouse models, mammalian cell culture and comparative epigenomics to answer the following questions:

1)    What are the functions of protein domains subject to diversification in chromatin modifying enzymes?

2)    Which evolutionary forces drive short histone H2A variants diversification in mammals?

3)    How do short H2As imprint parental epigenomes during mammalian reproduction?

4)    How does epigenome evolution shape normal development and disease progression in humans?


Press and other highlights of our work

Unususal Histones Mediate Parental Conflicts in Mammals (Fragile Nucleosome Seminar Series, 2021, Youtube)

The Secret Role Histones Played in Complex Cell Evolution (Wired, 2021, by Viviane Callier)

Fundamental proteins that guide embryo development are co-opted by cancer (Fred Hutch News, 2021, by Sabrina Richards)


The team

October 2022

March 2022

 Summer 2021

Research thematics


Last Name First Name Position Contact
Marine FRAISSE profile picture FRAISSE Marine Assistant Engineer
Germaine KARAM profile picture KARAM Germaine Assistant Engineer
Antoine MOLARO profile picture MOLARO Antoine Principal Investigator
Joris MORDIER profile picture MORDIER Joris Assistant Engineer


  • 2022
    • M. Cariou, L. Picard, L. Gueguen, S. Jacquet, A. Cimarelli, O. Fregoso, A. Molaro, V. Navratil and L. Etienne, “Distinct evolutionary trajectories of SARS-CoV-2-interacting proteins in bats and primates identify important host determinants of COVID-19.”, Proc. Natl. Acad. Sci. U.S.A., vol. 119 (35) , pp. e2206610119, 2022.
    • A. Osakabe and A. Molaro, “Histone renegades: Unusual H2A histone variants in plants and animals.”, Seminars in cell & developmental biology, 2022.
    • P. Raman, M. Rominger, J. Young, A. Molaro, T. Tsukiyama and H. Malik, “Novel Classes and Evolutionary Turnover of Histone H2B Variants in the Mammalian Germline.”, Molecular biology and evolution, vol. 39 (2) , 2022.
  • 2021
    • G. Chew, M. Bleakley, R. Bradley, H. Malik, S. Henikoff, A. Molaro and J. Sarthy, “Short H2A histone variants are expressed in cancer.”, Nature communications, vol. 12 (1) , pp. 490, 2021.
  • 2020
    • A. Molaro, A. Wood, D. Janssens, S. Kindelay, M. Eickbush, S. Wu, P. Singh, C. Muller, S. Henikoff and H. Malik, “Biparental contributions of the H2A.B histone variant control embryonic development in mice.”, PLoS biology, vol. 18 (12) , pp. e3001001, 2020.
    • P. Navarro-Costa, A. Molaro, C. Misra, C. Meiklejohn and P. Ellis, “Sex and suicide: The curious case of Toll-like receptors.”, PLoS biology, vol. 18 (3) , pp. e3000663, 2020.
    • A. Molaro, H. Malik and D. Bourc'his, “Dynamic evolution of de novo DNA methyltransferases in rodent and primate genomes.”, Molecular biology and evolution, 2020.
  • 2018
    • A. Molaro, J. Young and H. Malik, “Evolutionary origins and diversification of testis-specific short histone H2A variants in mammals.”, Genome Res., vol. 28 (4) , pp. 460–473, 2018.
    • J. Qu, E. Hodges, A. Molaro, P. Gagneux, M. Dean, G. Hannon and A. Smith, “Evolutionary expansion of DNA hypomethylation in the mammalian germline genome.”, Genome Res., vol. 28 (2) , pp. 145–158, 2018.
    • A. Molaro and I. Drinnenberg, “Studying the Evolution of Histone Variants Using Phylogeny.”, Meth. Mol. Biol., vol. 1832 , pp. 273–291, 2018.
  • 2017
    • A. Molaro and H. Malik, “Culture shock.”, eLife, vol. 6 , 2017.
  • 2016
    • A. Molaro and H. Malik, “Hide and seek: how chromatin-based pathways silence retroelements in the mammalian germline.”, Current opinion in genetics & development, vol. 37 , pp. 51–58, 2016.
  • 2014
    • A. Molaro, I. Falciatori, E. Hodges, A. Aravin, K. Marran, S. Rafii, W. McCombie, A. Smith and G. Hannon, “Two waves of de novo methylation during mouse germ cell development.”, Genes Dev., vol. 28 (14) , pp. 1544–9, 2014.
  • 2013
    • L. Kaaij, M. van de Wetering, F. Fang, B. Decato, A. Molaro, H. van de Werken, J. van Es, J. Schuijers, E. de Wit, W. de Laat, G. Hannon, H. Clevers, A. Smith and R. Ketting, “DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus.”, Genome biology, vol. 14 (5) , pp. R50, 2013.
  • 2012
    • F. Fang, E. Hodges, A. Molaro, M. Dean, G. Hannon and A. Smith, “Genomic landscape of human allele-specific DNA methylation.”, Proc. Natl. Acad. Sci. U.S.A., vol. 109 (19) , pp. 7332–7, 2012.
    • F. Muerdter, I. Olovnikov, A. Molaro, N. Rozhkov, B. Czech, A. Gordon, G. Hannon and A. Aravin, “Production of artificial piRNAs in flies and mice.”, RNA, vol. 18 (1) , pp. 42–52, 2012.
  • 2011
    • E. Hodges, A. Molaro, C. Dos Santos, P. Thekkat, Q. Song, P. Uren, J. Park, J. Butler, S. Rafii, W. McCombie, A. Smith and G. Hannon, “Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment.”, Molecular cell, vol. 44 (1) , pp. 17–28, 2011.
    • A. Molaro, E. Hodges, F. Fang, Q. Song, W. McCombie, G. Hannon and A. Smith, “Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates.”, Cell, vol. 146 (6) , pp. 1029–41, 2011.