Networks of Function and Shared Ancestry Provide Insights into Diversification of Histone Fold Domain in the Plant Kingdom

The Histone Fold Motif (HFM) of core histone proteins is one of the most highly conserved signature motifs in living organisms. Despite significant variation in sequence over millions of years of evolution, the HFM retains a distinctive structural fold that has diversified into several non-histone protein families. We have identified over 4000 HFM containing proteins in plants that are not histones, raising the question of why the family has expanded so considerably in the plant kingdom. We find that a majority of non-histone HFMs are playing regulatory roles, and that they are distributed widely within and across taxonomic groups. In this work we explore the relationships between the HFM of non-histones and that of their ancestral core histone forerunners, using a network approach. Networks of core histones and non-histone counterparts were superimposed with additional layers of complexity, like functional annotations, sub cellular locations, taxonomy and shared ancestry. HFM networks of model plants rice and Arabidopsis were investigated in terms of gene expression, interactions with other proteins as well as regulatory potential, to gain insights into diversification events during evolution that are not immediately evident from phylogenetic trees or raw data alone. Taken together, the networks elucidate diverse paths of evolution of the histone fold motif, leading to sub-functionalization and neo-functionalization of the HFM.