title: Evolutionary interrogation of human biology in well-annotated genomic framework of rhesus macaque.
abstract: With genome sequence and composition highly analogous to human, rhesus macaque represents a unique reference for evolutionary studies of human biology. Here, we developed a comprehensive genomic framework of rhesus macaque, the RhesusBase2, for evolutionary interrogation of human genes and the associated regulations. A total of 1,667 next-generation sequencing (NGS) data sets were processed, integrated, and evaluated, generating 51.2 million new functional annotation records. With extensive NGS annotations, RhesusBase2 refined the fine-scale structures in 30% of the macaque Ensembl transcripts, reporting an accurate, up-to-date set of macaque gene models. On the basis of these annotations and accurate macaque gene models, we further developed an NGS-oriented Molecular Evolution Gateway to access and visualize macaque annotations in reference to human orthologous genes and associated regulations (www.rhesusbase.org/molEvo). We highlighted the application of this well-annotated genomic framework in generating hypothetical link of human-biased regulations to human-specific traits, by using mechanistic characterization of the DIEXF gene as an example that provides novel clues to the understanding of digestive system reduction in human evolution. On a global scale, we also identified a catalog of 9,295 human-biased regulatory events, which may represent novel elements that have a substantial impact on shaping human transcriptome and possibly underpin recent human phenotypic evolution. Taken together, we provide an NGS data-driven, information-rich framework that will broadly benefit genomics research in general and serves as an important resource for in-depth evolutionary studies of human biology.
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Shi-Jian
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Chu-Jun
authors.initials: CJ
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhong
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Xinzhuang
authors.initials: X
authors.lastname: Yang
authors.forename: Jiguang
authors.initials: J
authors.lastname: Peng
authors.forename: Shouyu
authors.initials: S
authors.lastname: Yan
authors.forename: Chenqu
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xiong
authors.forename: Yong E
authors.initials: YE
authors.lastname: Zhang
authors.forename: Bertrand Chin-Ming
authors.initials: BC
authors.lastname: Tan
authors.forename: Chuan-Yun
authors.initials: CY
authors.lastname: Li
mesh_terms: D000818:Animals; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D015894:Genome, Human; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics*; D008957:Models, Genetic; D058977:Molecular Sequence Annotation; D013045:Species Specificity
keywords: RhesusBase; human evolution; human regulation; human-specific trait; next-generation sequencing; rhesus macaque