Functional and evolutionary implications of single nucleotide substitutions in human microRNAs across primates
MicroRNAs (miRNAs) are major contributors to phenotypic diversity and have a demonstrated role in evolution. We performed an analysis on how miRNA nucleotide substitutions may have contributed to human divergence from their closest primate relatives. We first studied the functional implications of a...
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| Tipo de documento: | tese |
| Estado: | Versão publicada |
| Data de publicação: | 2015 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositório: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/383030 |
| Acesso em linha: | http://hdl.handle.net/10803/383030 |
| Access Level: | Acceso aberto |
| Palavra-chave: | microRNAs Evolution Primates Non-coding RNAs Evolución Evolució RNAs no codificantes 575 |
| Resumo: | MicroRNAs (miRNAs) are major contributors to phenotypic diversity and have a demonstrated role in evolution. We performed an analysis on how miRNA nucleotide substitutions may have contributed to human divergence from their closest primate relatives. We first studied the functional implications of a substitution located in the seed region of mir-1304, reported to differ between present-day humans and Neandertals. We found a large change in the set of targets predicted for the two alleles, suggesting an important functional evolution for mir-1304. Among the few target genes predicted for the ancestral allele we found two genes involved in tooth development, ENAM and AMTN. Functional analysis revealed that these genes are differentially regulated by the two mir-1304 alleles suggesting that this change may have contributed to the modulation of phenotypic differences found between present-day humans and Neandertal dentitions. The thesis also offers a global view of the genetic diversification occurred in miRNA regions since the split of humans and chimpanzees. After careful alignment of all human miRNA sequences to chimpanzee and orangutan genomes, their substitution rates were calculated and compared between miRNA categories and with neutral sequences. Despite of the high conservation of these regulators, primate-specific miRNAs showed significantly higher substitution rates than more conserved miRNAs. This suggests that miRNA-driven evolution in primates could be partially sustained by mutation in novel, primate-specific miRNAs and that different miRNA categories show different evolutionary constraints and thus shall not be considered as an homogeneous group. |
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