Abstract
Nucleosomes, the basic repeat units of eukaryotic chromatin, have been suggested to influence the evolution of eukaryotic genomes, both by altering the propensity of DNA to mutate and by selection acting to maintain or exclude nucleosomes in particular locations. Contrary to the popular idea that nucleosomes are unique to eukaryotes, histone proteins have also been discovered in some archaeal genomes. Archaeal nucleosomes, however, are quite unlike their eukaryotic counterparts in many respects, including their assembly into tetramers (rather than octamers) from histone proteins that lack N- and C-terminal tails. Here, we show that despite these fundamental differences the association between nucleosome footprints and sequence evolution is strikingly conserved between humans and the model archaeon Haloferax volcanii. In light of this finding we examine whether selection or mutation can explain concordant substitution patterns in the two kingdoms. Unexpectedly, we find that neither the mutation nor the selection model are sufficient to explain the observed association between nucleosomes and sequence divergence. Instead, we demonstrate that nucleosome-associated substitution patterns are more consistent with a third model where sequence divergence results in frequent repositioning of nucleosomes during evolution. Indeed, we show that nucleosome repositioning is both necessary and largely sufficient to explain the association between current nucleosome positions and biased substitution patterns. This finding highlights the importance of considering the direction of causality between genetic and epigenetic change.
Highlights
Both in vitro and in vivo, nucleosomes are non-randomly positioned with regard to the underlying sequence, forming preferentially on stretches of DNA that – by virtue of their sequence composition – are more amenable to being wrapped around the histone core [1,2,3]
What is the causal relationship between the two? We already know that nucleotide variation within and between species is distributed unevenly around nucleosome footprints, but does this mean that sequence evolution follows a biased course because the presence of nucleosomes affects mutation and DNA repair dynamics? Or is it, the other way around, i.e. changes happen at the DNA level and prompt shifts in nucleosome positioning? To investigate the direction of causality in genetic versus epigenetic evolution, we analyze substitutions patterns in eukaryotes as well as the archaeon Haloferax volcanii in the context of genome-wide nucleosome binding maps
We demonstrate that the relationship between nucleosome positions and between-species divergence patterns, strikingly similar in eukaryotes and archaea, can be explained in large parts by nucleosomes shifting positions in response to substitution, both mutation and selection biases might still exist
Summary
Both in vitro and in vivo, nucleosomes are non-randomly positioned with regard to the underlying sequence, forming preferentially on stretches of DNA that – by virtue of their sequence composition – are more amenable to being wrapped around the histone core [1,2,3]. Changes at the sequence level during evolution can bring about changes in nucleosome positioning and occupancy [4,5], providing a simple example of how genetic changes can locally alter epigenetic states. The presence of nucleosomes can affect the efficacy of DNA repair by altering the structural context in which lesions need to be detected and removed [6]. Nucleosomes can affect evolution at the sequence level by modulating mutation and repair dynamics (thereby biasing the emergence of novel variants) and by exerting selective pressure on the underlying sequence (thereby altering fixation probabilities)
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