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PLoS One. 2016 Sep 22;11(9):e0163229. doi: 10.1371/journal.pone.0163229. eCollection 2016.

Molecular Evolution of MDM1, a "Duplication-Resistant" Gene in Vertebrates.

PloS one

Monica R Hensley, Rhys F M Chua, Yuk Fai Leung, Jer-Yen Yang, GuangJun Zhang

Affiliations

  1. Department of Comparative Pathobiology, Purdue University. West Lafayette, Indiana, United States of America.
  2. Department of Biological Sciences, Purdue University. West Lafayette, Indiana, United States of America.
  3. Purdue Institute for Integrative Neuroscience, Purdue University. West Lafayette, Indiana, United States of America.
  4. Department of Basic Medical Sciences, Purdue University. West Lafayette, Indiana, United States of America.
  5. Purdue University Center for Cancer Research. West Lafayette, Indiana, United States of America.
  6. Purdue Institute for Inflammation, Immunology and Infectious Diseases (PI4D), Purdue University. West Lafayette, Indiana, United States of America.

PMID: 27658201 PMCID: PMC5033493 DOI: 10.1371/journal.pone.0163229

Abstract

BACKGROUND: The mouse double minute 1 (Mdm1) gene was first reported and cloned in mouse tumor cell lines as an oncogene candidate. Later, it was found that mutation of Mdm1 might cause age-related retinal degeneration 2 in mice by genetic linkage analysis. Additionally, the MDM1 protein was found to be expressed in the centrosomes, cilia, and the nucleus of multiciliated tracheal epithelial cells in mice. These observations suggest that MDM1 may have some basal functions in cell physiology. However, the evolutionary history of this gene and its expression during embryonic development remain largely unexplored.

RESULTS: Using molecular phylogenetic analysis, we found that the MDM1 gene encoded an evolutionarily conserved protein across all metazoans. We also found that the MDM1 gene was in a conserved synteny in vertebrates. In almost all the species that were analyzed, there was only one MDM1 gene based on current genome annotations. Since vertebrate genomes underwent two to three rounds of whole-genome duplications around the origin of the vertebrates, it is interesting that only one MDM1 ohnolog was retained. This observation implies that other MDM1 ohnologs were lost after the whole-genome duplications. Furthermore, using whole-mount in situ hybridization, we found that mdm1 was expressed in the forebrain, nephric ducts, and tail buds during zebrafish early embryonic development.

CONCLUSION: MDM1 is an evolutionary conserved gene, and its homologous genes can be traced back to basal metazoan lineages. In vertebrates, the MDM1 gene is in a conserved synteny and there is only one MDM1 ohnolog suggesting it is a "duplication-resistant" gene. Its expression patterns in early zebrafish embryos indicate that mdm1 may play important roles in the development of the central nervous system, kidneys, and hematopoietic system.

Conflict of interest statement

The authors have declared that no competing interests exist.

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