Molecular evolution of multiple-level control of heme biosynthesis pathway in animal kingdom
Author
Tzou, Wen-Shyong
Chu, Ying
Lin, Tzung-Yi
Hu, Chin-Hwa
Pai, Tun-Wen
Liu, Hsin-Fu
Lin, Han-Jia
Cases, Ildeofonso
Rojas, Ana
Sanchez, Mayka
You, Zong-Ye
Hsu, Ming-Wei
Publication date
2014ISSN
1932-6203
Abstract
Adaptation of enzymes in a metabolic pathway can occur not only through changes in amino acid sequences but also through variations in transcriptional activation, mRNA splicing and mRNA translation. The heme biosynthesis pathway, a linear pathway comprised of eight consecutive enzymes in animals, provides researchers with ample information for multiple types of evolutionary analyses performed with respect to the position of each enzyme in the pathway. Through bioinformatics analysis, we found that the protein-coding sequences of all enzymes in this pathway are under strong purifying selection, from cnidarians to mammals. However, loose evolutionary constraints are observed for enzymes in which self-catalysis occurs. Through comparative genomics, we found that in animals, the first intron of the enzyme-encoding genes has been co-opted for transcriptional activation of the genes in this pathway. Organisms sense the cellular content of iron, and through iron-responsive elements in the 5′ untranslated regions of mRNAs and the intron-exon boundary regions of pathway genes, translational inhibition and exon choice in enzymes may be enabled, respectively. Pathway product (heme)-mediated negative feedback control can affect the transport of pathway enzymes into the mitochondria as well as the ubiquitin-mediated stability of enzymes. Remarkably, the positions of these controls on pathway activity are not ubiquitous but are biased towards the enzymes in the upstream portion of the pathway. We revealed that multiple-level controls on the activity of the heme biosynthesis pathway depend on the linear depth of the enzymes in the pathway, indicating a new strategy for discovering the molecular constraints that shape the evolution of a metabolic pathway.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
57 - Biological sciences in general
61 - Medical sciences
Keywords
Biosíntesi
Adaptació dels enzims
Aminoàcids
Enzims
Metabolisme
Biosíntesis
Adaptación de las enzimas
Aminoácidos
Enzimas
Metabolismo
Biosynthesis
Adaptation of enzymes
Amino acids
Enzymes
Metabolism
Pages
15
Publisher
Public Library of Science
Collection
9; 1
Is part of
PLoS One
Citation
Tzou, Wen-Shyong; Chu, Ying; Lin, Tzung-Yi [et al.]. Molecular evolution of multiple-level control of heme biosynthesis pathway in animal kingdom. PLoS ONE, 2014, 9(1): e86718. Disponible en: <https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086718>. Fecha de acceso: 17 ene. 2022. DOI: 10.1371/journal.pone.0086718
This item appears in the following Collection(s)
- Ciències de la Salut [738]
Rights
© 2014 Tzou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/