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The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that the motifs are contact points for ribosomal-RNA|messenger-RNA and messenger-RNA|messenger-RNA heteroduplexes, present in the binding sites of many RNA-binding proteins, and carried by endogenous small noncoding RNAs. Moreover, several of the motifs\u2019 intergenic copies overlap genome-wide association-study\u2013determined polymorphisms associated with brain disorders and other conditions. Lastly, based on expression data from bulk brain samples from autism spectrum disorder patients and controls, specific combinations of these motifs are enriched only among genes that are downregulated in the patients and only in the cortical areas that are responsible for language, hearing, and vision. This study shows that genomic architecture, the sequences of ribosomal RNAs\/spacers, and the sequences of nervous system genes have remained interlocked across 600 million years of evolution through organism-specific motifs. The findings suggest an extensive regulatory layer and can aid in developing new molecular diagnostics and treatments for disorders considered typically human.<\/jats:p>","DOI":"10.1093\/molbev\/msaf237","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T04:10:28Z","timestamp":1760328628000},"source":"Crossref","is-referenced-by-count":1,"title":["Organism-Specific Sequence Motifs Link Ribosomal RNAs to Brain Disorders"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1529-8631","authenticated-orcid":false,"given":"Isidore","family":"Rigoutsos","sequence":"first","affiliation":[{"name":"Computational Medicine Center, Thomas Jefferson University , Jefferson Alumni Hall #M81, 1020 Locust Street, Philadelphia, PA 19107 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