EVOLUTIONARY DYNAMICS OF THE U12-TYPE SPLICEOSOMAL INTRONS IN MULTICELLULAR ORGANISMS
Open Access
- Author:
- Lin, Chiao-Feng
- Graduate Program:
- Biology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 05, 2008
- Committee Members:
- Wojciech Makalowski, Committee Chair/Co-Chair
Edward C Holmes, Committee Chair/Co-Chair
Webb Colby Miller, Committee Member
Ross Cameron Hardison, Committee Member
Stephen M Mount, Committee Member - Keywords:
- spliceosomal introns
U12-type intron
intron evolution - Abstract:
- Many multicellular eukaryotes have two types of spliceosome for the removal of introns from messenger RNA precursors. The major (U2) -type spliceosome processes the vast majority of introns, while the minor (U12) -type spliceosome removes the small fraction (less than 0.5%) of introns referred to as U12-type introns. U12-type introns have distinct sequence elements, and mostly occur in genes together with U2-type introns. A phylogeny of species with and without U12-type introns shows that the minor splicing pathway has been lost repeatedly in evolution. With four parallel and one shared snRNPs, the two spliceosome function in a similar, cooperative, and competitive manner. The possibility of U12-introns converting to U2-type introns make the evolutionary dynamics of U12-type introns more complicated than just gain and loss. The studies in this thesis include computational identification and characterization of U12-type introns, and the evolutionary dynamics of U12-type introns. I have investigated the evolution of U12-type introns among 18 metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any species and only five show U12 to U2 conversion. In contrast to the other insect species investigated, Dipteran genomes are characterized by a rapid evolution (or loss) of components of the U12 spliceosome and a striking loss of U12-type introns. Nevertheless, we find one case of U2 to U12 conversion, apparently mediated by activation of a cryptic U12 splice site, in Diptera. Overall, loss of U12-type introns is more common than conversion to U2-type. U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype. I also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been reported previously. My most salient finding is that U12 introns are extremely stable in some taxa, including eutheria. U12-type intron loss is more frequent than conversion to the major type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.