ArticleProceedings of the National Academy of Sciences of the United States of America2011
Evolution of a derived protein-protein interaction between HoxA11 and Foxo1a in mammals caused by changes in intramolecular regulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 47 citations in OpenAlex.
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- Deregulation of the HOXA9/MEIS1 axis in acute leukemia.Current opinion in hematology · 2016Review
- Evolutionary Dynamics of Floral Homeotic Transcription Factor Protein-Protein Interactions.Molecular biology and evolution · 2016Article
- Functional Divergence of the Nuclear Receptor NR2C1 as a Modulator of Pluripotentiality During Hominid Evolution.Genetics · 2016Article
- Selection on different genes with equivalent functions: the convergence story told by Hox genes along the evolution of aquatic mammalian lineages.BMC evolutionary biology · 2016Article
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- Unraveling the Tangled Skein: The Evolution of Transcriptional Regulatory Networks in Development.Annual review of genomics and human genetics · 2015Review
- Rethinking gene regulatory networks in light of alternative splicing, intrinsically disordered protein domains, and post-translational modifications.Frontiers in cell and developmental biology · 2015Article
- Evolution of transcription factor function as a mechanism for changing metazoan developmental gene regulatory networks.EvoDevo · 2015Review
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- Modular evolution of DNA-binding preference of a Tbrain transcription factor provides a mechanism for modifying gene regulatory networks.Molecular biology and evolution · 2014Article
- Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.Cell · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current models of developmental evolution suggest changes in gene regulation underlie the evolution of morphology. Despite the fact that protein complexes regulate gene expression, the evolution of regulatory protein complexes is rarely studied. Here, we investigate the evolution of a protein-protein interaction (PPI) between Homeobox A11 (HoxA11) and Forkhead box 01A (Foxo1a). Using extant and "resurrected" ancestral proteins, we show that the physical interaction between HoxA11 and Foxo1a originated in the mammalian stem lineage. Functional divergence tests and coimmunoprecipitation with heterologous protein pairs indicate that the evolution of interaction was attributable to changes in HoxA11, and deletion studies demonstrate that the interaction interface is located in the homeodomain region of HoxA11. However, there are no changes in amino acid sequence in the homeodomain region during this time period, indicating that the origin of the derived PPI was attributable to changes outside the binding interface. We infer that the amino acid substitutions in HoxA11 altered Foxo1a's access to the conserved binding interface at the HoxA11 homeodomain. We also found an expansion in the number of paired Hox/Fox binding sites in the genomes of mammalian lineage species suggesting the complex has a biological function. Our data indicate that the physical interaction between HoxA11 and Foxo1a evolved through noninterface changes that facilitate the PPI, which prevents inappropriate interactions, rather than through the evolution of a novel binding interface. We speculate that evolutionary changes of intramolecular regulation have limited pleiotropic effects compared with changes to interaction domains themselves.
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