No evidence of paralogous loci or new bona fide microRNAs in telomere to telomere (T2T) genomic data

Abstract

The telomere to telomere (T2T) genome project discovered and mapped ∼240 million additional base pairs of primarily telomeric and centromeric reads. Much of this sequence was comprised of satellite sequences and large segmental duplications. We evaluated the extent to which human bona fide microRNAs (miRNAs) may be found in additional paralogous genomic loci or if previously undescribed microRNAs are present in these newly sequenced regions of the human genome. New genomic regions of the T2T project spanning ∼240 million bp of sequence were obtained and evaluated by blastn for the human miRNAs contained in MirGeneDB2.0 (N=556) and miRBase (N = 1917) along with all species of MirGeneDB2.0 miRNAs (N=10,899). Additionally, bowtie was used to compare unmapped reads from >4,000 primary cell samples to the new T2T sequence. Based on sequence and structure, no bona fide miRNAs were identified. Ninety-seven miRNAs of questionable authenticity (frequently known repeat elements) were identified from the miRBase dataset across the newly described regions of the human genome. These 97 represent only 51 miRNA families due to paralogy of highly similar miRNAs such as 24 members of the hsa-mir-548 family. Altogether, this data strongly supports our having identified widely expressed bona fide miRNAs in the human genome and move us further toward the completion of human miRNA discovery.