Long Non-Coding RNAs in Primate Brain Evolution

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Long non-coding RNAs (lncRNAs) have been identified as key players in the nervous system. Tens of thousands of lncRNAs are expressed in the brain, contribute to important brain functions and show associations with neurodegenerative and psychiatric diseases. Despite considerable efforts, there is still a large gap in the structural and in particular functional annotation of lncRNAs limiting our understanding of their role in the nervous system. Many characteristics of the brain are human specific. Genes that evolve quickly, as lncRNAs do, are therefore the best candidates to be primarily responsible for the evolution of these innovations. Since biological function has to be studied in the light of evolution, we aim here at establishing a full catalog of human lncRNAs, including an annotation of their sequence, structure, expression, and evolutionary changes by collating and coherently re-analyzing the wealth of already available high throughout data. In the first funding phase we have compiled a catalog of evolutionarily young, mostly brain-related lncRNAs, developed a generic, efficient algorithm for the reconstruction of transcript structures from diverse RNA-Seq data, and devised a statistical test for positive selection on lncRNAs. On this basis, we now want to focus on the functional evolution of lncRNAs. We propose to investigate evolutionary changes in lncRNAs across mammals including archaic humans, develop methods for distinguishing lncRNAs that function primarily based on their structure vs. on their primary sequence, predict and compare lncRNA target genes in primates, and relate evolutionary changes to complex brainfunctions and disorders. It is further our goal to provide our lncRNA catalog with its detailed annotations and functional information to the scientific community in a user-friendly manner.