Comparative studies of microRNA transcription start sites between human and chimpanzee

• Main Authors: Cheng-Kuo Lai, 賴政國
• Other Authors: Li-Ching Hsieh
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/86666970495841783343

碩士 === 國立中興大學 === 基因體暨生物資訊學研究所 === 103 === Identifying the transcription start sites (TSSs) of microRNA (miRNA) genes is essential for understanding the regulation of miRNA transcription which is extremely important for determining the specific roles that miRNAs play in regulatory pathways. Because humans and chimpanzees share most of genes, comparative studies of the two species are the ways often used to comprehend humans more. In the past, most studies are focused on the divergence of proteins, genes and miRNAs. However, the divergence of the regulation of miRNA transcription between humans and chimpanzees seems still not to be addressed yet. In this study, 86 global-run-on-sequencing (GRO-Seq) validated TSSs of 125 human miRNAs were collected to search their homologous regions in the chimpanzee genome. An un-annotated homologous miRNA region was considered to be a putative chimpanzee miRNA if the sequence of the region can be folded into a hairpin structure. In addition, a homologous TSS location was then confirmed as a putative chimpanzee miRNA TSS if it was able to be identified by a semi-supervised statistical model trained on Pol II ChIP-sequencing data of chimpanzee and several sequence-associated features. From the result, most of the human TSS-miRNA pairs are still kept in chimpanzees. We identified 33 un-annotated chimpanzee miRNAs and 48 putative chimpanzee miRNA TSSs of 69 chimpanzee miRNAs. Interestingly, a number of human TSS-miRNA pairs were missing; we found that 18 miRNAs were lost in chimpanzee during evolution and another missing miRNA, mir-659, might be human specific. We studied the regulatory pathway of mir-659 and found that mir-659 could be involved in neurodevelopmental. These divergence of the regulation of miRNA transcription might be, at least in part, the molecular footprint of speciation events in the human and chimpanzee lineages.