PUBLICATION
Identification of hidden associations among eukaryotic genes through statistical analysis of coevolutionary transitions
- Authors
- Dembech, E., Malatesta, M., De Rito, C., Mori, G., Cavazzini, D., Secchi, A., Morandin, F., Percudani, R.
- ID
- ZDB-PUB-251120-14
- Date
- 2023
- Source
- Proceedings of the National Academy of Sciences of the United States of America 120: e2218329120e2218329120 (Journal)
- Registered Authors
- Keywords
- coevolution, gene association, glyoxylate cycle, purine catabolism, statistical significance
- MeSH Terms
-
- Phylogeny
- Evolution, Molecular*
- Eukaryotic Cells
- Eukaryota*/genetics
- PubMed
- 37043529 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Dembech, E., Malatesta, M., De Rito, C., Mori, G., Cavazzini, D., Secchi, A., Morandin, F., Percudani, R. (2023) Identification of hidden associations among eukaryotic genes through statistical analysis of coevolutionary transitions. Proceedings of the National Academy of Sciences of the United States of America. 120:e2218329120e2218329120.
Abstract
Coevolution at the gene level, as reflected by correlated events of gene loss or gain, can be revealed by phylogenetic profile analysis. The optimal method and metric for comparing phylogenetic profiles, especially in eukaryotic genomes, are not yet established. Here, we describe a procedure suitable for large-scale analysis, which can reveal coevolution based on the assessment of the statistical significance of correlated presence/absence transitions between gene pairs. This metric can identify coevolution in profiles with low overall similarities and is not affected by similarities lacking coevolutionary information. We applied the procedure to a large collection of 60,912 orthologous gene groups (orthogroups) in 1,264 eukaryotic genomes extracted from OrthoDB. We found significant cotransition scores for 7,825 orthogroups associated in 2,401 coevolving modules linking known and unknown genes in protein complexes and biological pathways. To demonstrate the ability of the method to predict hidden gene associations, we validated through experiments the involvement of vertebrate malate synthase-like genes in the conversion of (S)-ureidoglycolate into glyoxylate and urea, the last step of purine catabolism. This identification explains the presence of glyoxylate cycle genes in metazoa and suggests an anaplerotic role of purine degradation in early eukaryotes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping