Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K
- University of Dundee, United Kingdom
- University of Oxford, United Kingdom
Abstract
Eukaryotic genes are interrupted by introns that are removed from transcribed RNAs by splicing. Patterns of splicing complexity differ between species, but it is unclear how these differences arise. We used inter-species association mapping with Saccharomycotina species to correlate splicing signal phenotypes with the presence or absence of splicing factors. Here we show that variation in 5' splice site sequence preferences correlate with the presence of the U6 snRNA N6-methyladenosine methyltransferase METTL16 and the splicing factor SNRNP27K. The greatest variation in 5' splice site sequence occurred at the +4 position and involved a preference switch between adenosine and uridine. Loss of METTL16 and SNRNP27K orthologs, or a single SNRNP27K methionine residue, was associated with a preference for +4U. These findings are consistent with splicing analyses of mutants defective in either METTL16 or SNRNP27K orthologs and models derived from spliceosome structures, demonstrating that inter-species association mapping is a powerful orthogonal approach to molecular studies. We identified variation between species in the occurrence of two major classes of 5' splice sites, defined by distinct interaction potentials with U5 and U6 snRNAs, that correlates with intron number. We conclude that variation in concerted processes of 5' splice site selection by U6 snRNA is associated with evolutionary changes in splicing signal phenotypes.
Data availability
This study uses the publicly available genome sequences of 240 different species. The details of the previously used data sets corresponding to these 240 genome sequences are reported in Supplementary File 1.
Article and author information
Author details
Gordon Grant Simpson
Funding
Biotechnology and Biological Sciences Research Council (BB/V010662/1)
- Gordon Grant Simpson
Biotechnology and Biological Sciences Research Council (BB/W007673/1)
- Geoffrey J Barton
- Gordon Grant Simpson
Wellcome Trust (220212/Z/20/Z)
- Sebastian M Fica
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Parker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K
eLife 12:e91997.
https://doi.org/10.7554/eLife.91997
