数字农科院2.0

Evolution and function of developmentally dynamic pseudogenes in mammals

文献类型： 外文期刊

作者： Sheng Hu Qian; Lu Chen; Yu‑Li Xiong and Zhen‑Xia Chen

关键词： Pseudogene; Developmentally dynamic expression; Mammals; Evolution; Iso-seq

期刊名称： GENOME BIOLOGY

ISSN： 1474-760X

年卷期： 2022 年

页码：

收录情况： SCIE（2022版）

摘要： Background: Pseudogenes are excellent markers for genome evolution, which are emerging as crucial regulators of development and disease, especially cancer. However, systematic functional characterization and evolution of pseudogenes remain largely unexplored. Results: To systematically characterize pseudogenes, we date the origin of human and mouse pseudogenes across vertebrates and observe a burst of pseudogene gain in these two lineages. Based on a hybrid sequencing dataset combining full-length PacBio sequencing, sample-matched Illumina sequencing, and public time-course transcriptome data, we observe that abundant mammalian pseudogenes could be transcribed, which contribute to the establishment of organ identity. Our analyses reveal that developmentally dynamic pseudogenes are evolutionarily conserved and show an increasing weight during development. Besides, they are involved in complex transcriptional and post-transcriptional modulation, exhibiting the signatures of func‑ tional enrichment. Coding potential evaluation suggests that 19% of human pseudo‑ genes could be translated, thus serving as a new way for protein innovation. Moreover, pseudogenes carry disease-associated SNPs and conduce to cancer transcriptome perturbation. Conclusions: Our discovery reveals an unexpectedly high abundance of mammalian pseudogenes that can be transcribed and translated, and these pseudogenes rep‑ resent a novel regulatory layer. Our study also prioritizes developmentally dynamic pseudogenes with signatures of functional enrichment and provides a hybrid sequenc‑ ing dataset for further unraveling their biological mechanisms in organ development and carcinogenesis in the future.

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