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Computational identification and evolutionaty enalysis of metazoan micrornas

MicroRNAs are a large family of 21-26 nucleotide non-coding RNAs with a
role in the post-transcriptional regulation of gene expression. In recent years,
microRNAs have been proposed to play a significant role in the expansion of
organism complexity. MicroRNAs are expressed in a cell or tissue-specific manner
during embryonic development, suggesting a role in cellular differentiation. For
example, Let-7 is a metazoan microRNA that acts as developmental timer between
larval stages in C. elegans. We conducted a comparative study that determined the
distribution of microRNA families among metazoans, including the identification of
new family members for several species. MicroRNA families appear to have evolved
in bursts of evolution that correlate with the advent of major metazoan groups such
as vertebrates, eutherians, primates and hominids. Most microRNA families identified
in these organisms appeared with or after the advent of vertebrates. Only a few of
them appear to be shared between vertebrates and invertebrates. The distribution of
these microRNA families supports the idea that at least one whole genome
duplication event (WGS) predates the advent of vertebrates. Gene ontology analyses of the genes these microRNA families regulate show enrichments for functions
related to cell differentiation and morphogenesis.
MicroRNA genes appear to be under great selective constraints. Identification
of conserved regions by comparative genomics allows for the computational
identification of microRNAs. We have identified and characterized ultraconserved
regions between the genomes of the honey bee (Apis mellifera) and the parasitic wasp
(Nasonia vitripennis), and developed a strategy for the identification of microRNAs
based on regions of ultraconservation. Ultraconserved regions preferentially localize
within introns and intergenic regions, and are enriched in functions related to neural
development. Introns harboring ultraconserved elements appear to be under negative
selection and under a level of constraint that is higher than in their exonic
counterparts. This level of constraint suggests functional roles yet to be discovered
and suggests that introns are major players in the regulation of biological processes.
Our computational strategy was able to identify new microRNA genes shared
between honey bee and wasp. We recovered 41 of 45 previously validated
microRNAs for these organisms, and we identified several new ones. A significant
fraction of these microRNA candidates are located in introns and intergenic regions
and are organized in genomic clusters. Expression of 13 of these new candidates was
verified by 454 sequencing.

Identiferoai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-3115
Date15 May 2009
CreatorsAnzola Lagos, Juan Manuel
ContributorsAramayo, Rodolfo, Elsik, Christine
Source SetsTexas A and M University
Languageen_US
Detected LanguageEnglish
TypeBook, Thesis, Electronic Dissertation, text
Formatelectronic, application/pdf, born digital

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