Our article culminates from a 4-years-long study in our lab. It focuses on histone H2A.B, a member of short H2A histone variants that arose on the X-chromosome of placental mammals, where they are predominantly expressed in testes. 2/
Histones, variants carry out deeply conserved functions, but short H2A variants are subject to unprecedented levels of diversification and gene turnover, leading us to hypothesize that short H2As are engaged in ongoing genetic conflicts https://genome.cshlp.org/content/early/2018/03/16/gr.229799.117 3/
My favorite hypothesis was meiotic drive because H2A.B is encoded on X chromosomes. However, 2 years in, following the lab's first (expensive) foray into mouse genetics, our main hypothesis was dead in the water; no evidence of meiotic drive 4/
To his credit, @AntoineMolaro pushed past the disappointment and considered a different model: battle between parents for resource allocation post-fertilization. This is the primary driver for things like DNA methylation based genomic imprinting of parental alleles 5/
Indeed, @AntoineMolaro @annajwood2 used a genetic strategy generating genotypically identical zygotes but from genetically distinct fathers or mothers to show an unambiguous role for the paternal and maternal contribution of H2A.B in dictating embryonic fitness. 6/
We then collaborated with the Henikoff lab to show that H2A.B affects genome-wide chromatin compaction in male germ cells, suggesting that H2A.B act as a global germ cell imprint that function post-fertilization 7/
Final note: many research studies challenge you intellectually, but this one did so pyschologically as well (for me). Full credit to @AntoineMolaro for persisting and discovering a completely novel function for a histone variant /fin
I should mention that if you are a prospective student or postdoc who is interested in this chromatin-mediated negotiation for mammalian development, @AntoineMolaro is looking for new lab members in beautiful Clermont-Ferrand: https://www.gred-clermont.fr/directory/team/en/team-15-evolutionary-epigenomics-and-genetic-conflicts/
You can follow @HarmitMalik.
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