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Cell. 2018 Apr 19;173(3):749-761.e38. doi: 10.1016/j.cell.2018.03.007. Epub 2018 Mar 29.

Evolutionary Convergence of Pathway-Specific Enzyme Expression Stoichiometry.

Author information

1
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: gwli@mit.edu.

Abstract

Coexpression of proteins in response to pathway-inducing signals is the founding paradigm of gene regulation. However, it remains unexplored whether the relative abundance of co-regulated proteins requires precise tuning. Here, we present large-scale analyses of protein stoichiometry and corresponding regulatory strategies for 21 pathways and 67-224 operons in divergent bacteria separated by 0.6-2 billion years. Using end-enriched RNA-sequencing (Rend-seq) with single-nucleotide resolution, we found that many bacterial gene clusters encoding conserved pathways have undergone massive divergence in transcript abundance and architectures via remodeling of internal promoters and terminators. Remarkably, these evolutionary changes are compensated post-transcriptionally to maintain preferred stoichiometry of protein synthesis rates. Even more strikingly, in eukaryotic budding yeast, functionally analogous proteins that arose independently from bacterial counterparts also evolved to convergent in-pathway expression. The broad requirement for exact protein stoichiometries despite regulatory divergence provides an unexpected principle for building biological pathways both in nature and for synthetic activities.

KEYWORDS:

Enzyme expression stoichiometry; Rend-seq; end-enriched RNA-seq; operon evolution; ribosome profiling

PMID:
29606352
PMCID:
PMC5978003
[Available on 2019-04-19]
DOI:
10.1016/j.cell.2018.03.007
[Indexed for MEDLINE]

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