B. Morgenstern et Wr. Atchley, Evolution of bHLH transcription factors: Modular evolution by domain shuffling?, MOL BIOL EV, 16(12), 1999, pp. 1654-1663
Multidomain proteins usually contain several conserved and apparently indep
endently evolved domains. As a result, classifications based on only a sing
le small domain may obscure the true evolutionary relationships of the prot
eins. The current classification of basic helix-loop-helix (bHLH) domain-co
ntaining proteins is based on the conserved bHLH domain alone. Herein, we e
xplore whether sequence homology and, therefore, evolutionary relationships
can be detected among the flanking or non-bHLH components of the amino aci
d sequences of 122 bHLH proteins. These 122 proteins were the same proteins
previously used to construct the existing classification of the bHLH-domai
n-containing proteins. Several possible scenarios are examined in order to
explain the observed patterns of sequence divergence, including (1) monophy
ly, (2) convergent evolution, (3) addition of functional components to the
bHLH domain, and (4) modular evolution with domain shuffling. Drawing on se
veral lines of evidence, we suggest that modular evolution by domain shuffl
ing may have played an important role in the evolution of this large group
of transcriptional regulators.