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Multiple independent evolutionary solutions to core histone gene regulation

Leonardo Mariño-Ramírez1, I King Jordan2 and David Landsman1*

Author Affiliations

1 Computational Biology Branch, National Center for Biotechnology Information, National Institutes of Health, 8600 Rockville Pike, Bethesda, Maryland 20894-6075, USA

2 School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, Georgia 30332-0230, USA

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Genome Biology 2006, 7:R122  doi:10.1186/gb-2006-7-12-r122

Published: 21 December 2006



Core histone genes are periodically expressed along the cell cycle and peak during S phase. Core histone gene expression is deeply evolutionarily conserved from the yeast Saccharomyces cerevisiae to human.


We evaluated the evolutionary dynamics of the specific regulatory mechanisms that give rise to the conserved histone regulatory phenotype. In contrast to the conservation of core histone gene expression patterns, the core histone regulatory machinery is highly divergent between species. There has been substantial evolutionary turnover of cis-regulatory sequence motifs along with the transcription factors that bind them. The regulatory mechanisms employed by members of the four core histone families are more similar within species than within gene families. The presence of species-specific histone regulatory mechanisms is opposite to what is seen at the protein sequence level. Core histone proteins are more similar within families, irrespective of their species of origin, than between families, which is consistent with the shared common ancestry of the members of individual histone families. Structure and sequence comparisons between histone families reveal that H2A and H2B form one related group whereas H3 and H4 form a distinct group, which is consistent with the nucleosome assembly dynamics.


The dissonance between the evolutionary conservation of the core histone gene regulatory phenotypes and the divergence of their regulatory mechanisms indicates a highly dynamic mode of regulatory evolution. This distinct mode of regulatory evolution is probably facilitated by a solution space for promoter sequences, in terms of functionally viable cis-regulatory sites, that is substantially greater than that of protein sequences.