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Despite the importance of gene regulatory enhancers in human biology and evolution, we lack a comprehensive model of enhancer evolution and function. This substantially limits our understanding of the genetic basis of species divergence and our ability to interpret the effects of noncoding variants on human traits. To explore enhancer sequence evolution and its relationship to regulatory function, we traced the evolutionary origins of transcribed human enhancer sequences with activity across diverse tissues and cellular contexts from the FANTOM5 consortium. The transcribed enhancers are enriched for sequences of a single evolutionary age ("simple" evolutionary architectures) compared with enhancers that are composites of sequences of multiple evolutionary ages ("complex" evolutionary architectures), likely indicating constraint against genomic rearrangements. Complex enhancers are older, more pleiotropic, and more active across species than simple enhancers. Genetic variants within complex enhancers are also less likely to associate with human traits and biochemical activity. Transposable-element-derived sequences (TEDS) have made diverse contributions to enhancers of both architectures; the majority of TEDS are found in enhancers with simple architectures, while a minority have remodeled older sequences to create complex architectures. Finally, we compare the evolutionary architectures of transcribed enhancers with histone-mark-defined enhancers. Our results reveal that most human transcribed enhancers are ancient sequences of a single age, and thus the evolution of most human enhancers was not driven by increases in evolutionary complexity over time. Our analyses further suggest that considering enhancer evolutionary histories provides context that can aid interpretation of the effects of variants on enhancer function. Based on these results, we propose a framework for analyzing enhancer evolutionary architecture.
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http://dx.doi.org/10.1093/molbev/msab138 | DOI Listing |
Plant Mol Biol
December 2024
Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, 210014, China.
Dioscorea alata, a key tuber crop for global food security, is threatened by anthracnose disease caused by Colletotrichum gloeosporioides. However, identification of functional resistance genes against C. gloeosporioides in D.
View Article and Find Full Text PDFCurr Biol
December 2024
School of the Environment and Life Sciences, University of Portsmouth, Burnaby Road, Portsmouth PO1 3QL, UK.
The Cambrian explosion was a time of groundbreaking ecological shifts related to the establishment of the Phanerozoic biosphere. Trace fossils, which are the products of animals interacting with their substrates, provide a key record of the diversification of the benthos and the evolution of behavioral complexity through this interval. The Chapel Island Formation of Newfoundland in Canada hosts the most extensive trace-fossil record from the latest Ediacaran to Cambrian Age 2, spanning about 20 million years continuously.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Dept. of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA.
Homologous recombination is a key evolutionary force that varies considerably across bacterial species. However, how the landscape of homologous recombination varies across genes and within individual genomes has only been studied in a few species. Here, we used Approximate Bayesian Computation to estimate the recombination rate along the genomes of 145 bacterial species.
View Article and Find Full Text PDFJ Chem Theory Comput
December 2024
Department of Physics, School of Physical Science and Technology, Ningbo University, Ningbo 315211, P.R. China.
The evolution of photosynthetic reaction centers (RCs) from anoxygenic bacteria to higher-order oxygenic cynobacteria and plants highlights a remarkable journey of structural and functional diversification as an adaptation to environmental conditions. The role of chirality in these centers is important, influencing the arrangement and function of key molecules involved in photosynthesis. Investigating the role of chirality may provide a deeper understanding of photosynthesis and the evolutionary history of life on Earth.
View Article and Find Full Text PDFNat Commun
December 2024
Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, 82152, Planegg-Martinsried, Germany.
The eukaryotic nucleus exhibits a highly organized 3D genome architecture, with RNA transcription and processing confined to specific nuclear structures. While intra-chromosomal interactions, such as promoter-enhancer dynamics, are well-studied, the role of inter-chromosomal interactions remains poorly understood. Investigating these interactions in mammalian cells is challenging due to large genome sizes and the need for deep sequencing.
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