Journal of Molecular Evolution

, Volume 49, Issue 3, pp 301–309

Molecular Evolution of Helix–Turn–Helix Proteins

  • James A.  Rosinski
  • William R.  Atchley

DOI: 10.1007/PL00006552

Cite this article as:
Rosinski, J. & Atchley, W. J Mol Evol (1999) 49: 301. doi:10.1007/PL00006552


The helix–turn–helix domain-containing family of transcriptional regulators is of ancient origin and has been incorporated into numerous disparate biological processes. As a consequence, the forces shaping its early evolution have been difficult to reconstruct. Herein, we analyze this large and diverse family with a combination of traditional phylogenetic techniques and newer sequence analysis tools to determine whether the helix–turn–helix family arose from a single common ancestor. Our analyses of the DNA-binding domain show that amino acid chemistry is conserved at many sites in the first helix and the turn. The high level of divergence combined with the short length of the domain hinders robust reconstruction of the entire phylogeny, but some level of deep node inference is possible. All analyses point to a predominantly monophyletic origin for the helix–turn–helix domain. The consequences of such an origin for a diverse group of proteins, and guidelines for the identification of future members of the HTH family are discussed.

Key words: Helix–turn–helix — Homology — Phylogeny — Transcription factors — Sequence shuffling 

Copyright information

© Springer-Verlag New York Inc. 1999

Authors and Affiliations

  • James A.  Rosinski
    • 1
  • William R.  Atchley
    • 1
  1. 1.Department of Genetics, North Carolina State University, Raleigh, NC 27695, USAUS