Molecular Evolution of MDM1, a “Duplication-Resistant” Gene in Vertebrates

Abstract

BackgroundThe 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.ResultsUsing 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.ConclusionMDM1 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.

Phylogenetic and developmental analyses indicate complex functions of calcium‐activated potassium channels in zebrafish embryonic development

“…Whole‐mount in situ hybridizations were performed according to the previous published method with some modifications. 23 , 56 Briefly, zebrafish embryos were collected, maintained, and staged according to the zebrafish development staging guide. 49 Chorions were removed using pronase (Sigma) treatment before fixation.…”

Loss of smarcad1a accelerates tumorigenesis of malignant peripheral nerve sheath tumors in zebrafish

“…Then, the riboprobes were purified by SigmaSpin™ post‐reaction clean‐up columns (Sigma, S5059). Whole‐mount in situ hybridization was carried out according to our previously published method 54,55 . For histological analysis, post‐hybridization embryos were equilibrated in 15% sucrose, then 30% sucrose in 20% gelatin, after which they were embedded in 20% gelatin for cryosectioning (6–12 μm).…”

Evolution of inwardly rectifying potassium channels and their gene expression in zebrafish embryos

“…Phylogenetic and syntenic analyses were performed as we described previously 49,57‐60 . Briefly, multiple protein sequences were aligned using MUSCLE program 61 .…”

“…Phylogenetic and syntenic analyses were performed as we described previously. 49,[57][58][59][60] Briefly, multiple protein sequences were aligned using MUSCLE program. 61 To identify the best evolutionary model for phylogenetic analysis, we carried out the best model test using maximum likelihood (ML) and default parameters in MEGA6.…”

“…Whole-mount in situ hybridizations were performed according to our established method with some modifications. 49,59,60 Briefly, zebrafish embryos were collected, maintained, and staged according to the zebrafish development staging guide. 56 Chorions were using pronase (Sigma) treatment before fixation for 1 to 3 dpf fish embryos.…”