RESUMO
BACKGROUND: To investigate the mechanisms driving regulatory evolution across tissues, we experimentally mapped promoters, enhancers, and gene expression in the liver, brain, muscle, and testis from ten diverse mammals. RESULTS: The regulatory landscape around genes included both tissue-shared and tissue-specific regulatory regions, where tissue-specific promoters and enhancers evolved most rapidly. Genomic regions switching between promoters and enhancers were more common across species, and less common across tissues within a single species. Long Interspersed Nuclear Elements (LINEs) played recurrent evolutionary roles: LINE L1s were associated with tissue-specific regulatory regions, whereas more ancient LINE L2s were associated with tissue-shared regulatory regions and with those switching between promoter and enhancer signatures across species. CONCLUSIONS: Our analyses of the tissue-specificity and evolutionary stability among promoters and enhancers reveal how specific LINE families have helped shape the dynamic mammalian regulome.
Assuntos
Evolução Molecular , Regulação da Expressão Gênica , Elementos Nucleotídeos Longos e Dispersos , Mamíferos/genética , Sequências Reguladoras de Ácido Nucleico , Retroelementos , Animais , Mapeamento Cromossômico , Sequência Conservada , Elementos Facilitadores Genéticos , Humanos , Especificidade de Órgãos/genética , Regiões Promotoras GenéticasRESUMO
Advances in synthetic biology and microbiology have enabled the creation of engineered bacteria which can sense and report on intracellular and extracellular signals. When deployed in vivo these whole-cell bacterial biosensors can act as sentinels to monitor biomolecules of interest in human health and disease settings. This is particularly interesting in the context of the gut microbiota, which interacts extensively with the human host throughout time and transit of the gut and can be accessed from feces without requiring invasive collection. Leveraging rational engineering approaches for genetic circuits as well as an expanding catalog of disease-associated biomarkers, bacterial biosensors can act as non-invasive and easy-to-monitor reporters of the gut. Here, we summarize recent engineering approaches applied in vivo in animal models and then highlight promising technologies for designing the next generation of bacterial biosensors.
