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bioRxiv · 10.1101/026013

Evolutionary dynamics of roX lncRNA function and genomic occupancy

Jeffrey Jerome Quinn·Qiangfeng C Zhang·Plamen Georgiev·Ibrahim A Ilik·Asifa Akhtar·Howard Y Chang
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Abstract

Many long noncoding RNAs (lncRNAs) can regulate chromatin states, but the evolutionary origin and dynamics driving lncRNA-genome interactions are unclear. We developed an integrative strategy that identifies lncRNA orthologs in different species despite limited sequence similarity that is applicable to fly and mammalian lncRNAs. Analysis of the roX lncRNAs, which are essential for dosage compensation of the single X-chromosome in Drosophila males, revealed 47 new roX orthologs in diverse Drosophilid species across ~40 million years of evolution. Genetic rescue by roX orthologs and engineered synthetic lncRNAs showed that evolutionary maintenance of focal structural repeats mediates roX function. Genomic occupancy maps of roX RNAs in four species revealed rapid turnover of individual binding sites but conservation within nearby chromosomal neighborhoods. Many new roX binding sites evolved from DNA encoding a pre-existing RNA splicing signal, effectively linking dosage compensation to transcribed genes. Thus, evolutionary analysis illuminates the principles for the birth and death of lncRNAs and their genomic targets.

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Jeffrey Jerome Quinn, Qiangfeng C Zhang, Plamen Georgiev, Ibrahim A Ilik, Asifa Akhtar, Howard Y Chang. 2015-09-04. Evolutionary dynamics of roX lncRNA function and genomic occupancy. https://doi.org/10.1101/026013

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