Intrinsic cooperativity potentiates parallel cis-regulatory evolution
- University of California, San Francisco, United States
- Vanderbilt University School of Medicine, United States
Abstract
Convergent evolutionary events in independent lineages provide an opportunity to understand why evolution favors certain outcomes over others. We studied such a case where a large set of genes-those coding for the ribosomal proteins-gained cis-regulatory sequences for a particular transcription regulator (Mcm1) in independent fungal lineages. We present evidence that these gains occurred because Mcm1 shares a mechanism of transcriptional activation with an ancestral regulator of the ribosomal protein genes, Rap1. Specifically, we show that Mcm1 and Rap1 have the inherent ability to cooperatively activate transcription through contacts with the general transcription factor TFIID. Because the two regulatory proteins share a common interaction partner, the presence of one ancestral cis-regulatory sequence can 'channel' random mutations into functional sites for the second regulator. At a genomic scale, this type of intrinsic cooperativity can account for a pattern of parallel evolution involving the fixation of hundreds of substitutions.
Data availability
Interspecies hybrid expression data is available at the Gene Expression Omnibus (GEO) repository under accession number GSE108389. Flow cytometry data is available at Flow Repository under accession numbers FR-FCM-ZYWS, FR-FCM-ZYWT, FR-FCM-ZYWU, FR-FCM-ZYWV, FR-FCM-ZYJZ, FR-FCM-ZYJY, and FR-FCM-ZYJ2. Code used in computational analyses is available at doi.org/10.5281/zenodo.1341284.
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Interspecies hybrid expression dataPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE108389).
Article and author information
Author details
Funding
National Institutes of Health (GM115892)
- Amanda N Johnson
- Jordan T Feigerle
- P Anthony Weil
National Institutes of Health (GM037049)
- Trevor R Sorrells
- Conor J Howard
- Candace S Britton
- Kyle R Fowler
- Alexander D Johnson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Sorrells 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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Intrinsic cooperativity potentiates parallel cis-regulatory evolution
eLife 7:e37563.
https://doi.org/10.7554/eLife.37563
Further reading
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- Chromosomes and Gene Expression
- Evolutionary Biology
Gene regulation is essential for life and controlled by regulatory DNA. Mutations can modify the activity of regulatory DNA, and also create new regulatory DNA, a process called regulatory emergence. Non-regulatory and regulatory DNA contain motifs to which transcription factors may bind. In prokaryotes, gene expression requires a stretch of DNA called a promoter, which contains two motifs called –10 and –35 boxes. However, these motifs may occur in both promoters and non-promoter DNA in multiple copies. They have been implicated in some studies to improve promoter activity, and in others to repress it. Here, we ask whether the presence of such motifs in different genetic sequences influences promoter evolution and emergence. To understand whether and how promoter motifs influence promoter emergence and evolution, we start from 50 ‘promoter islands’, DNA sequences enriched with –10 and –35 boxes. We mutagenize these starting ‘parent’ sequences, and measure gene expression driven by 240,000 of the resulting mutants. We find that the probability that mutations create an active promoter varies more than 200-fold, and is not correlated with the number of promoter motifs. For parent sequences without promoter activity, mutations created over 1500 new –10 and –35 boxes at unique positions in the library, but only ~0.3% of these resulted in de-novo promoter activity. Only ~13% of all –10 and –35 boxes contribute to de-novo promoter activity. For parent sequences with promoter activity, mutations created new –10 and –35 boxes in 11 specific positions that partially overlap with preexisting ones to modulate expression. We also find that –10 and –35 boxes do not repress promoter activity. Overall, our work demonstrates how promoter motifs influence promoter emergence and evolution. It has implications for predicting and understanding regulatory evolution, de novo genes, and phenotypic evolution.
