title: Exploring the Mutational Robustness of Nucleic Acids by Searching Genotype Neighborhoods in Sequence Space.
abstract: To assess the mutational robustness of nucleic acids, many genome- and protein-level studies have been performed, where nucleic acids are treated as genetic information carriers and transferrers. However, the molecular mechanisms through which mutations alter the structural, dynamic, and functional properties of nucleic acids are poorly understood. Here we performed a SELEX in silico study to investigate the fitness distribution of the l-Arm-binding aptamer genotype neighborhoods. Two novel functional genotype neighborhoods were isolated and experimentally verified to have comparable fitness as the wild-type. The experimental aptamer fitness landscape suggests the mutational robustness is strongly influenced by the local base environment and ligand-binding mode, whereas bases distant from the binding pocket provide potential evolutionary pathways to approach the global fitness maximum. Our work provides an example of successful application of SELEX in silico to optimize an aptamer and demonstrates the strong sensitivity of mutational robustness to the site of genetic variation.
authors.affiliation: iHuman Institute, ShanghaiTech University , Shanghai 201210, China.
authors.forename: Qingtong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Xianbao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University , Wuxi, Jiangsu 214122, China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Xia
authors.affiliation: iHuman Institute, ShanghaiTech University , Shanghai 201210, China.|Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China.|University of Chinese Academy of Sciences , Beijing 100049, China.|School of Life Science and Technology, ShanghaiTech University , Shanghai 201210, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fan
authors.affiliation: School of Life Science, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Luo
authors.affiliation: iHuman Institute, ShanghaiTech University , Shanghai 201210, China.|School of Life Science and Technology, ShanghaiTech University , Shanghai 201210, China.
authors.forename: Suwen
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Eugene
authors.identifier: http://orcid.org/0000-0002-5087-5724
authors.initials: E
authors.lastname: Shakhnovich
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Haojun
authors.initials: H
authors.lastname: Liang