Project description:A major challenge in biology is to determine how evolutionarily novel characters originate, however, mechanistic explanations for the origin of novelties are almost completely unknown. The evolution of mammalianM-BM- pregnancy is an excellent system in which to study the origin of novelties because extant mammals preserve major stages in the transition from egg-laying to live-birth. To determine the molecular bases of this transition we characterized the pregnant/gravid uterine transcriptome from tetrapods, including species in the three major mammalian lineages, and used ancestral transcriptome reconstruction to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including numerous genes that mediate maternal-fetal communication and immunotolerance.Furthermore we show that thousands of regulatory elements active inM-BM- decidualized human endometrial stromal cellsM-BM- are derived from ancient mammalian transposable elements which provided binding sites for transcription factors that mediate decidualization and endometrial cell-type identity.M-BM- Our results indicate that one of the defining mammalian novelties evolved via domestication of ancient mammalian transposable elements into hormone-responsive regulatory elements throughout the genome. Examination of histone modification and DNAse hypersensitivity in decidualized dESC
Project description:A major challenge in biology is to determine how evolutionarily novel characters originate, however, mechanistic explanations for the origin of novelties are almost completely unknown. The evolution of mammalian pregnancy is an excellent system in which to study the origin of novelties because extant mammals preserve major stages in the transition from egg-laying to live-birth. To determine the molecular bases of this transition we characterized the pregnant/gravid uterine transcriptome from tetrapods, including species in the three major mammalian lineages, and used ancestral transcriptome reconstruction to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including numerous genes that mediate maternal-fetal communication and immunotolerance.Furthermore we show that thousands of regulatory elements active in decidualized human endometrial stromal cells are derived from ancient mammalian transposable elements which provided binding sites for transcription factors that mediate decidualization and endometrial cell-type identity. Our results indicate that one of the defining mammalian novelties evolved via domestication of ancient mammalian transposable elements into hormone-responsive regulatory elements throughout the genome.
Project description:Suspended animation (e.g. hibernation, diapause) allows organisms to survive extreme environments. But the mechanisms underlying the evolution of suspended animation states are unknown. The African turquoise killifish has evolved diapause as a form of suspended development to survive the complete drought that occurs every summer. Here, we show that gene duplicates – paralogs – exhibit specialized expression in diapause compared to normal development in the African turquoise killifish. Surprisingly, paralogs with specialized expression in diapause are evolutionarily very ancient and are present even in vertebrates that do not exhibit diapause. To determine if evolution of diapause is due to the regulatory landscape rewiring at ancient paralogs, we assessed chromatin accessibility genome-wide in fish species with or without diapause. This analysis revealed an evolutionary recent increase in chromatin accessibility at very ancient paralogs in African turquoise killifish. The increase in chromatin accessibility is linked to the presence of new binding sites for transcription factors, likely due to de novo mutations and transposable element (TE) insertion. Interestingly, accessible chromatin regions in diapause are enriched for lipid metabolism genes, and our lipidomics studies uncover a striking difference in lipid species in African turquoise killifish diapause, which could be critical for long-term survival. Together, our results show that diapause likely originated by repurposing pre-existing gene programs via recent changes in the regulatory landscape. This work raises the possibility that suspended animation programs could be reactivated in other species for long-term preservation via transcription factor remodeling and suggests a mechanism for how complex adaptations evolve in nature.
Project description:A major challenge in biology is to determine how evolutionarily novel characters originate, however, mechanistic explanations for the origin of novelties are almost completely unknown. The evolution of mammalian pregnancy is an excellent system in which to study the origin of novelties because extant mammals preserve major stages in the transition from egg-laying to live-birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods, including species in the three major mammalian lineages, and used ancestral transcriptome reconstruction to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved or lost uterine expression during the origins of mammalian pregnancy, including the loss of genes responsible for the mineralization of the eggshell in the Mammalian and Therian stem-lineages, and the recruitment of genes into uterine expression that mediate maternal-fetal communication and maternal immunotolerance of the fetal allograft in the Therian and Eutherian stem-lineages. Our results indicate that one of the defining mammalian novelties evolved through a step-wise process that dramatically changed uterine gene expression, generating a suite of evolutionary innovations that support prolonged gestations. We report genome-wide gene expression generated by mRNA-Seq from the pregnant endometrium of dog, armadillo, and the platypus.
Project description:A major challenge in biology is to determine how evolutionarily novel characters originate, however, mechanistic explanations for the origin of novelties are almost completely unknown. The evolution of mammalian pregnancy is an excellent system in which to study the origin of novelties because extant mammals preserve major stages in the transition from egg-laying to live-birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods, including species in the three major mammalian lineages, and used ancestral transcriptome reconstruction to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved or lost uterine expression during the origins of mammalian pregnancy, including the loss of genes responsible for the mineralization of the eggshell in the Mammalian and Therian stem-lineages, and the recruitment of genes into uterine expression that mediate maternal-fetal communication and maternal immunotolerance of the fetal allograft in the Therian and Eutherian stem-lineages. Our results indicate that one of the defining mammalian novelties evolved through a step-wise process that dramatically changed uterine gene expression, generating a suite of evolutionary innovations that support prolonged gestations.
Project description:Arbuscular mycorrhizal (AM) fungi form mutualistic relationships with most land plant species. AM fungi have long been considered as ancient asexuals. Long-term clonal evolution would be remarkable for a eukaryotic lineage and suggests the importance of alternative mechanisms to promote genetic variability facilitating adaptation. Here, we assessed the potential of transposable elements (TEs) for generating genomic diversity. The dynamic expression of TEs during Rhizophagus irregularis spore development suggests ongoing TE activity. We find Mutator-like elements located near genes belonging to highly expanded gene families. Characterising the epigenomic status of R. irregularis provides evidence of DNA methylation and small RNA production occurring at TE loci. Our results support a potential role for TEs in shaping the genome, and roles for DNA methylation and small RNA-mediated silencing in regulating TEs. A well-controlled balance between TE activity and repression may therefore contribute to genome evolution in AM fungi.
Project description:Transposable elements (TEs) appear to have contributed to the evolution of tissue-specific gene regulatory networks in contexts such as early development, pregnancy and innate immunity, amongst others. In mouse embryonic stem cells (ESCs), TE families such as RLTR13D6 bind key pluripotency-associated transcription factors and are enriched for histone marks that are characteristic of distal enhancers. However, it remains unclear to what extent such lineage-specific TEs are important for maintaining gene expression programmes during preimplantation development. Here we have tested the gene regulatory function of RLTR13D6 elements in ESCs using epigenetic editing approaches. Whilst we identify some elements that are important to drive gene expression, these constitute a minority of all the putative TE-derived enhancers identified through epigenomic analyses, highlighting the importance of functional tests when assessing the contribution of TEs to gene regulatory networks.
Project description:Transposable elements (TEs) appear to have contributed to the evolution of tissue-specific gene regulatory networks in contexts such as early development, pregnancy and innate immunity, amongst others. In mouse embryonic stem cells (ESCs), TE families such as RLTR13D6 bind key pluripotency-associated transcription factors and are enriched for histone marks that are characteristic of distal enhancers. However, it remains unclear to what extent such lineage-specific TEs are important for maintaining gene expression programmes during preimplantation development. Here we have tested the gene regulatory function of RLTR13D6 elements in ESCs using epigenetic editing approaches. Whilst we identify some elements that are important to drive gene expression, these constitute a minority of all the putative TE-derived enhancers identified through epigenomic analyses, highlighting the importance of functional tests when assessing the contribution of TEs to gene regulatory networks.
Project description:Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise overall, contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires across five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous genes from different species. Even the circRNAs from shared loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution – as a byproduct of splicing in orthologs prone to transposable element insertion. Overall, our findings argue against widespread functional circRNA conservation.
Project description:Mammalian embryo development is dependent on the ability of the uterus to allow and support the implantation of the embryo. Here we demonstrate that ablation of Sox17 specifically in the uterine epithelium results in altered uterine epithelial cell proliferation, uterine gland development and embryo implantation. Uteri lacking Sox17 showed reduction in LIF and IHH signaling which are critical for embryo implantation. ChIP-seq analysis demonstrated that SOX17 binds to a region 19kb 5’ to the Ihh locus. In vivo deletion of this enhancer by the CRISPR-Cas technology reduced Ihh expression in uteri and altered proper endometrial epithelial-stromal interactions required for pregnancy leading to compromised fertility. The SOX17 binding peak at 19kb from the Ihh promoter also bound GATA2, FOXA2 and PGR. Bioinformatic analysis of regions overlapping SOX17, GATA2, FOXA2 and PGR bindings shows 737 genes with these common binding sites. This cluster of transcription factors identified in this enhancer region may represent a combination of regulatory elements essential for uterine epithelial gene expression and differentiation.