Complex Evolutionary History of the Mammalian Histone H1.1-H1.5 Gene Family

Abstract

H1 is involved in chromatin higher-order structure and gene regulation. H1 has a tripartite structure. The central domain is stably folded in solution, while the N- and C-terminal domains are intrinsically disordered. The terminal domains are encoded by DNA of low sequence complexity, and are thus prone to short insertions/deletions (indels). We have examined the evolution of the H1.1-H1.5 gene family from 27 mammalian species. Multiple sequence alignment has revealed a strong preferential conservation of the number and position of basic residues among paralogs, suggesting that overall H1 basicity is under a strong purifying selection. The presence of a conserved pattern of indels, ancestral to the splitting of mammalian orders, in the N- and C-terminal domains of the paralogs, suggests that slippage may have favored the rapid divergence of the subtypes and that purifying selection has maintained this pattern because it is associated with function. Evolutionary analyses have found evidences of positive selection events in H1.1, both before and after the radiation of mammalian orders. Positive selection ancestral to mammalian radiation involved changes at specific sites that may have contributed to the low relative affinity of H1.1 for chromatin. More recent episodes of positive selection were detected at codon positions encoding amino acids of the C-terminal domain of H1.1, which may modulate the folding of the CTD. The detection of putative recombination points in H1.1-H1.5 subtypes suggests that this process may has been involved in the acquisition of the tripartite H1 structure.

Keywords: functional differentiation; histone H1; insertions/deletions; maximum-likelihood analysis; positive selection.; recombination.