RT Journal Article
SR Electronic
T1 Optimizing gene expression by adapting splicing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 220228
DO 10.1101/220228
A1 Idan Frumkin
A1 Ido Yofe
A1 Raz Bar-Ziv
A1 Yoav Voichek
A1 Yitzhak Pilpel
YR 2017
UL http://biorxiv.org/content/early/2017/11/15/220228.abstract
AB Can splicing be used by cells to adapt to new environmental challenges? While various adaptation mechanisms for regulating gene expression have been revealed for transcription and translation, the role of splicing and how it evolves to optimize gene-expression patterns has not been thoroughly investigated. To tackle this question, we employed a lab-evolution experimental approach that challenged yeast cells to increase expression levels of a gene that carries an inefficiently-spliced intron. We followed the evolution of multiple lines and found independent routes by which cells adapted. Surprisingly, we did not observe an intron loss event, a mechanism believed to be common in intron evolution. Instead, we identified mutations in cis that improved the intron’s splicing efficiency and increased the overall expression level of the entire gene. One of these cis-acting mutations occurred in an adjacent exon and hampered the functionality of the gene that was not under selection - demonstrating that adaptation of splicing efficiency may sometimes come at the expense of protein activity. Additionally, we observed adaptations in trans, which increased the cellular availability of the splicing machinery. These adaptations were achieved either by elevated expression levels of the splicing apparatus or, unexpectedly, by reduced expression levels of other intron-containing genes that are the natural consumers of this process. Ultimately, our work reveals novel molecular means by which the splicing machinery is changed by natural selection to optimize gene-expression patterns of cells.