title: Evolution of the Max and Mlx networks in animals.
abstract: Transcription factors (TFs) are essential for the regulation of gene expression and often form emergent complexes to perform vital roles in cellular processes. In this paper, we focus on the parallel Max and Mlx networks of TFs because of their critical involvement in cell cycle regulation, proliferation, growth, metabolism, and apoptosis. A basic-helix-loop-helix-zipper (bHLHZ) domain mediates the competitive protein dimerization and DNA binding among Max and Mlx network members to form a complex system of cell regulation. To understand the importance of these network interactions, we identified the bHLHZ domain of Max and Mlx network proteins across the animal kingdom and carried out several multivariate statistical analyses. The presence and conservation of Max and Mlx network proteins in animal lineages stemming from the divergence of Metazoa indicate that these networks have ancient and essential functions. Phylogenetic analysis of the bHLHZ domain identified clear relationships among protein families with distinct points of radiation and divergence. Multivariate discriminant analysis further isolated specific amino acid changes within the bHLHZ domain that classify proteins, families, and network configurations. These analyses on Max and Mlx network members provide a model for characterizing the evolution of TFs involved in essential networks.
authors.affiliation: Bioinformatics Research Center, North Carolina State University, USA. lisa.mcferrin@gmail.com
authors.forename: Lisa G
authors.initials: LG
authors.lastname: McFerrin
authors.forename: William R
authors.initials: WR
authors.lastname: Atchley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000737:chemistry / Q000235:genetics*; D050976:Basic-Leucine Zipper Transcription Factors / Q000145:classification / Q000235:genetics*; D001665:Binding Sites; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D026801:Synteny / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; C403128:MLX protein, human; C067850:Myc associated factor X