Evolution of high mobility group nucleosome-binding proteins and its implications for vertebrate chromatin specialization

Mol Biol Evol. 2015 Jan;32(1):121-31. doi: 10.1093/molbev/msu280. Epub 2014 Oct 3.


High mobility group (HMG)-N proteins are a family of small nonhistone proteins that bind to nucleosomes (N). Despite the amount of information available on their structure and function, there is an almost complete lack of information on the molecular evolutionary mechanisms leading to their exclusive differentiation. In the present work, we provide evidence suggesting that HMGN lineages constitute independent monophyletic groups derived from a common ancestor prior to the diversification of vertebrates. Based on observations of the functional diversification across vertebrate HMGN proteins and on the extensive silent nucleotide divergence, our results suggest that the long-term evolution of HMGNs occurs under strong purifying selection, resulting from the lineage-specific functional constraints of their different protein domains. Selection analyses on independent lineages suggest that their functional specialization was mediated by bursts of adaptive selection at specific evolutionary times, in a small subset of codons with functional relevance-most notably in HMGN1, and in the rapidly evolving HMGN5. This work provides useful information to our understanding of the specialization imparted on chromatin metabolism by HMGNs, especially on the evolutionary mechanisms underlying their functional differentiation in vertebrates.

Keywords: HMGN; chromatin; episodic adaptive selection; high mobility group proteins; long-term evolution; nucleosome-binding domain; purifying selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / metabolism*
  • Evolution, Molecular
  • HMGN Proteins / chemistry*
  • HMGN Proteins / genetics*
  • HMGN Proteins / metabolism
  • Humans
  • Models, Molecular
  • Phylogeny
  • Selection, Genetic
  • Vertebrates / genetics
  • Vertebrates / metabolism*


  • Chromatin
  • HMGN Proteins