title: Emergence, Retention and Selection: A Trilogy of Origination for Functional De Novo Proteins from Ancestral LncRNAs in Primates.
abstract: While some human-specific protein-coding genes have been proposed to originate from ancestral lncRNAs, the transition process remains poorly understood. Here we identified 64 hominoid-specific de novo genes and report a mechanism for the origination of functional de novo proteins from ancestral lncRNAs with precise splicing structures and specific tissue expression profiles. Whole-genome sequencing of dozens of rhesus macaque animals revealed that these lncRNAs are generally not more selectively constrained than other lncRNA loci. The existence of these newly-originated de novo proteins is also not beyond anticipation under neutral expectation, as they generally have longer theoretical lifespan than their current age, due to their GC-rich sequence property enabling stable ORFs with lower chance of non-sense mutations. Interestingly, although the emergence and retention of these de novo genes are likely driven by neutral forces, population genetics study in 67 human individuals and 82 macaque animals revealed signatures of purifying selection on these genes specifically in human population, indicating a proportion of these newly-originated proteins are already functional in human. We thus propose a mechanism for creation of functional de novo proteins from ancestral lncRNAs during the primate evolution, which may contribute to human-specific genetic novelties by taking advantage of existed genomic contexts.
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Qing Sunny
authors.initials: QS
authors.lastname: Shen
authors.affiliation: Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Wei-Zhen
authors.initials: WZ
authors.lastname: Zhou
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Jiguang
authors.initials: J
authors.lastname: Peng
authors.affiliation: FAS Center for Systems Biology & Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Bin Z
authors.initials: BZ
authors.lastname: He
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Chu-Jun
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Xuke
authors.initials: X
authors.lastname: Luan
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Ding
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Bertrand Chin-Ming
authors.initials: BC
authors.lastname: Tan
authors.affiliation: Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yong E
authors.initials: YE
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Aibin
authors.initials: A
authors.lastname: He
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Chuan-Yun
authors.initials: CY
authors.lastname: Li
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D020862:GC Rich Sequence / Q000235:genetics; D005828:Genetics, Population; D015894:Genome, Human; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics; D016366:Open Reading Frames; D010802:Phylogeny; D011323:Primates / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding