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Genome-wide evolution analysis reveals low CpG contents of fast-evolving genes and identifies antiviral microRNAs
Affiliation:1. MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China;2. Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structures, Tsinghua University, Beijing, 100084, China;3. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China;4. Center for Infectious Disease Research, Tsinghua University, Beijing, 100084, China;5. Tsinghua-Peking Center for Life Sciences, Beijing, 100084, China;1. Vinmec Research Institute of Stem Cell and Gene Technology (VRSIG), 458 Minh Khai, Vinh Tuy, Hai Ba Trung, Hanoi, Viet Nam;2. Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH, 44106, USA;1. Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, 22904 USA;2. Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22904 USA
Abstract:Noncoding RNAs(ncRNAs) play important roles in many biological processes and provide materials for evolutionary adaptations beyond protein-coding genes, such as in the arms race between the host and pathogen. However, currently, a comprehensive high-resolution analysis of primate genomes that includes the latest annotated ncRNAs is not available. Here, we developed a computational pipeline to estimate the selections that act on noncoding regions based on comparisons with a large number of reference sequences in introns adjacent to the interested regions. Our method yields result comparable with those of the established codon-based method and phyloP method for coding genes; thus, it provides a holistic framework for estimating the selection on the entire genome. We further showed that fastevolving protein-coding genes and their corresponding 50 UTRs have a significantly lower frequency of the CpG dinucleotides than those evolving at an average pace, and these fast-evolving genes are enriched in the process of immunity and host defense. We also identified fast-evolving miRNAs with antiviral functions in cells. Our results provide a resource for high-resolution evolution analysis of the primate genomes.
Keywords:Host-virus interaction  Positive selection  CpG dinucleotide  Noncoding RNA  MicroRNA
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