Evolution of the vertebrate H1 histone class: evidence for the functional differentiation of the subtypes

Histone H1 subtypes are involved in chromatin higher-order structure. The representation of the subtypes varies greatly depending on the cellular and developmental context. We have estimated the rates of nucleotide substitution for several H1 subtypes, including mammalian and amphibian H1 degree, avian H5, and mammalian H1a-e and H1t, with the aim of finding evidence for their functional differentiation. The rates of nonsynonymous substitution differ among the subtypes by almost one order of magnitude. Such a wide variation in the degree of tolerance of amino acid substitutions is consistent with the functional differentiation of the subtypes. H1 has a characteristic three-domain structure. The rate ratios among the domains of the molecule are not systematically maintained in the different subtypes. This suggests the assumption of differentiated functions by the individual domains in chromatin structure. We have estimated the average time of divergence of H1a-e and H1t paralogs as 406 +/- 80 Myr. The lack of evidence for concerted evolution of H1a-e and H1t since long before the mammalian radiation further supports the functional differentiation of the subtypes.