title: Expression profile and gene age jointly shaped the genome-wide distribution of premature termination codons in a Drosophila melanogaster population.
abstract: Widespread premature termination codon mutations (PTCs) were recently observed in human and fly populations. We took advantage of the population resequencing data in the Drosophila Genetic Reference Panel to investigate how the expression profile and the evolutionary age of genes shaped the allele frequency distribution of PTCs. After generating a high-quality data set of PTCs, we clustered genes harboring PTCs into three categories: genes encoding low-frequency PTCs (≤ 1.5%), moderate-frequency PTCs (1.5-10%), and high-frequency PTCs (>10%). All three groups show narrow transcription compared with PTC-free genes, with the moderate- and high-PTC frequency groups showing a pronounced pattern. Moreover, nearly half (42%) of the PTC-encoding genes are not expressed in any tissue. Interestingly, the moderate-frequency PTC group is strongly enriched for genes expressed in midgut, whereas genes harboring high-frequency PTCs tend to have sex-specific expression. We further find that although young genes born in the last 60 My compose a mere 9% of the genome, they represent 16%, 30%, and 50% of the genes containing low-, moderate-, and high-frequency PTCs, respectively. Among DNA-based and RNA-based duplicated genes, the child copy is approximately twice as likely to contain PTCs as the parent copy, whereas young de novo genes are as likely to encode PTCs as DNA-based duplicated new genes. Based on these results, we conclude that expression profile and gene age jointly shaped the landscape of PTC-mediated gene loss. Therefore, we propose that new genes may need a long time to become stably maintained after the origination.
authors.affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents & Key Laboratory of the Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Haiwang
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents & Key Laboratory of the Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China FAS Center for Systems Biology & Howard Hughes Medical Institute, Harvard University.
authors.forename: Bin Z
authors.initials: BZ
authors.lastname: He
authors.affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents & Key Laboratory of the Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Huijing
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Mathematics and Science, National Taiwan Normal University, New Taipei City, Taiwan, Republic of China.
authors.forename: Shun-Chern
authors.initials: SC
authors.lastname: Tsaur
authors.affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents & Key Laboratory of the Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Life Science, Genome and Systems Biology Degree Program, Institute of Ecology and Evolutionary Biology, Institute of Zoology, and Research Center for Developmental Biology and Regeneration Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Chau-Ti
authors.initials: CT
authors.lastname: Ting
authors.affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents & Key Laboratory of the Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China zhangyong@ioz.ac.cn.
authors.forename: Yong E
authors.initials: YE
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002875:Chromosomes; D018389:Codon, Nonsense; D019295:Computational Biology / Q000379:methods*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution
chemical_list: D018389:Codon, Nonsense; D029721:Drosophila Proteins
keywords: gene duplication; gene loss; midgut; premature termination codon; young gene