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Molecular evolution of multiple-level control of heme biosynthesis pathway in animal kingdom.
- Source :
-
PloS one [PLoS One] 2014 Jan 28; Vol. 9 (1), pp. e86718. Date of Electronic Publication: 2014 Jan 28 (Print Publication: 2014). - Publication Year :
- 2014
-
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.
- Subjects :
- 5' Untranslated Regions genetics
Amino Acid Motifs
Amino Acid Sequence
Amino Acids genetics
Animals
Base Sequence
Conserved Sequence genetics
Deoxyribonucleases metabolism
Exons genetics
Genes
Introns genetics
Molecular Sequence Data
Response Elements genetics
Selection, Genetic
Sequence Alignment
Biosynthetic Pathways genetics
Evolution, Molecular
Heme biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24489775
- Full Text :
- https://doi.org/10.1371/journal.pone.0086718