Contrasting Patterns in the Evolution of Vertebrate MLX Interacting Protein (MLXIP) and MLX Interacting Protein-Like (MLXIPL) Genes

PLoS One. 2016 Feb 24;11(2):e0149682. doi: 10.1371/journal.pone.0149682. eCollection 2016.

Abstract

ChREBP and MondoA are glucose-sensitive transcription factors that regulate aspects of energy metabolism. Here we performed a phylogenomic analysis of Mlxip (encoding MondoA) and Mlxipl (encoding ChREBP) genes across vertebrates. Analysis of extant Mlxip and Mlxipl genes suggests that the most recent common ancestor of these genes was composed of 17 coding exons. Single copy genes encoding both ChREBP and MondoA, along with their interacting partner Mlx, were found in diverse vertebrate genomes, including fish that have experienced a genome duplication. This observation suggests that a single Mlx gene has been retained to maintain coordinate regulation of ChREBP and MondoA. The ChREBP-β isoform, the more potent and constitutively active isoform, appeared with the evolution of tetrapods and is absent from the Mlxipl genes of fish. Evaluation of the conservation of ChREBP and MondoA sequences demonstrate that MondoA is better conserved and potentially mediates more ancient function in glucose metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Evolution, Molecular*
  • Exons / physiology
  • Gene Dosage / physiology
  • Glucose / genetics*
  • Glucose / metabolism
  • Humans
  • Mice
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MLXIP protein, human
  • MLXIPL protein, human
  • Mlxipl protein, mouse
  • MondoA protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • Glucose

Grants and funding

This work was funded by a National Science Foundation of China (NSFC) – Canadian Institutes of Health Research (CIHR) China – Canada Joint Health Research Initiative grant from the Canadian Institutes of Health Research (http://www.cihr-irsc.gc.ca/e/193.html), grant number CCI -109605 to DMI. Parmveer Singh was supported by a Banting and Best Diabetes Summer Studentship (www.bbdc.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.