Birth-and-death evolution with strong purifying selection in the histone H1 multigene family and the origin of orphon H1 genes

Histories are small basic nuclear proteins with critical structural and functional roles in eukaryotic genomes. The HI multigene family constitutes a very interesting histone class gathering the greatest number of isoforms, with many different arrangements in the genome, including clustered and solitary genes, and showing replication-dependent (RD) or replication-independent (RI) expression patterns. The evolution of HI histones has been classically explained by concerted evolution through a rapid process of interlocus recombination or gene conversion. Given such intriguing features, we have analyzed the long-term evolutionary pattern of the HI multigene family through the evaluation of the relative importance of gene conversion, point mutation, and selection in generating and maintaining the different HI subtypes. We have found the presence of an extensive silent nucleotide divergence, both within and between species, which is always significantly greater than the nonsilent variation, indicating that purifying selection is the major factor maintaining HI protein homogeneity. The results obtained from phylogenctic analysis reveal that different HI subtypes are no more closely related within than between species, as they cluster by type in the topologies, and that both RD and RI HI variants follow the same evolutionary pattern. These findings suggest that HI histones have not been subject to any significant effect of interlocus recombination or concerted evolution. However, the diversification of the HI isoforms seems to be enhanced primarily by mutation and selection, where genes are subject to birth-and-death evolution with strong purifying selection at the protein level. This model is able to explain not only the generation and diversification of RD HI isoforms but also the origin and long-term persistence of orphon RI H I subtypes in the genome, something that is still unclear, assuming concerted evolution.