1. Chromosomes and Gene Expression
  2. Microbiology and Infectious Disease
Download icon

Codon choice directs constitutive mRNA levels in trypanosomes

  1. Janaina de Freitas Nascimento
  2. Steven Kelly
  3. Jack Sunter
  4. Mark Carrington  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Oxford, United Kingdom
Research Article
  • Cited 27
  • Views 2,228
  • Annotations
Cite this article as: eLife 2018;7:e32467 doi: 10.7554/eLife.32467

Abstract

Selective transcription of individual protein coding genes does not occur in trypanosomes and the cellular copy number of each mRNA must be determined post-transcriptionally. Here, we provide evidence that codon choice directs the levels of constitutively expressed mRNAs. First, a novel codon usage metric, the gene expression codon adaptation index (geCAI), was developed that maximised the relationship between codon choice and the measured abundance for a transcriptome. Second, geCAI predictions of mRNA levels were tested using differently coded GFP transgenes and were successful over a 25-fold range, similar to the variation in endogenous mRNAs. Third, translation was necessary for the accelerated mRNA turnover resulting from codon choice. Thus, in trypanosomes, the information determining the levels of most mRNAs resides in the open reading frame and translation is required to access this information.

Data availability

The following previously published data sets were used

Article and author information

Author details

  1. Janaina de Freitas Nascimento

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Steven Kelly

    Department of Plant Sciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8583-5362
  3. Jack Sunter

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Mark Carrington

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    mc115@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6435-7266

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

  • Janaina de Freitas Nascimento

Cambridge Overseas Trust

  • Janaina de Freitas Nascimento

Wellcome (085956/Z/08/Z)

  • Mark Carrington

Biotechnology and Biological Sciences Research Council

  • Jack Sunter

Horizon 2020 Framework Programme (637765)

  • Jack Sunter

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: October 3, 2017
  2. Accepted: February 27, 2018
  3. Accepted Manuscript published: March 15, 2018 (version 1)
  4. Version of Record published: April 11, 2018 (version 2)

Copyright

© 2018, de Freitas Nascimento 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.

Metrics

  • 2,228
    Page views
  • 335
    Downloads
  • 27
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Chromosomes and Gene Expression
    2. Evolutionary Biology
    Mathias Scharmann et al.
    Research Article Updated

    Differences between males and females are usually more subtle in dioecious plants than animals, but strong sexual dimorphism has evolved convergently in the South African Cape plant genus Leucadendron. Such sexual dimorphism in leaf size is expected largely to be due to differential gene expression between the sexes. We compared patterns of gene expression in leaves among 10 Leucadendron species across the genus. Surprisingly, we found no positive association between sexual dimorphism in morphology and the number or the percentage of sex-biased genes (SBGs). Sex bias in most SBGs evolved recently and was species specific. We compared rates of evolutionary change in expression for genes that were sex biased in one species but unbiased in others and found that SBGs evolved faster in expression than unbiased genes. This greater rate of expression evolution of SBGs, also documented in animals, might suggest the possible role of sexual selection in the evolution of gene expression. However, our comparative analysis clearly indicates that the more rapid rate of expression evolution of SBGs predated the origin of bias, and shifts towards bias were depleted in signatures of adaptation. Our results are thus more consistent with the view that sex bias is simply freer to evolve in genes less subject to constraints in expression level.

    1. Chromosomes and Gene Expression
    2. Plant Biology
    Jaemyung Choi et al.
    Research Article

    Flowering plants utilize small RNA molecules to guide DNA methyltransferases to genomic sequences. This RNA-directed DNA methylation (RdDM) pathway preferentially targets euchromatic transposable elements. However, RdDM is thought to be recruited by methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin. How RdDM is targeted to euchromatin despite an affinity for H3K9me is unclear. Here we show that loss of histone H1 enhances heterochromatic RdDM, preferentially at nucleosome linker DNA. Surprisingly, this does not require SHH1, the RdDM component that binds H3K9me. Furthermore, H3K9me is dispensable for RdDM, as is CG DNA methylation. Instead, we find that non-CG methylation is specifically associated with small RNA biogenesis, and without H1 small RNA production quantitatively expands to non-CG methylated loci. Our results demonstrate that H1 enforces the separation of euchromatic and heterochromatic DNA methylation pathways by excluding the small RNA-generating branch of RdDM from non-CG methylated heterochromatin.