Journal Article

Evolution of the Max and Ml<span class="smallCaps">x</span> Networks in Animals

Lisa G. McFerrin and William R. Atchley

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 3, issue , pages 915-937
Published in print January 2011 |
Published online August 2011 | e-ISSN: 1759-6653 | DOI:

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  • Bioinformatics and Computational Biology
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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.

Keywords: protein evolution; basic-helix-loop-helix-leucine zipper (bHLHZ) domain; Myc/Max/Mad network; Mlx and Mondo Network; phylogenetic tree; discriminant analysis

Journal Article.  13130 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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