Genetic Variability of the Functional Domains of Chromodomains Helicase DNA-Binding (CHD) Proteins

Genes (Basel). 2021 Nov 19;12(11):1827. doi: 10.3390/genes12111827.


In the past few years, there has been an increasing neuroscientific interest in understanding the function of mammalian chromodomains helicase DNA-binding (CHD) proteins due to their association with severe developmental syndromes. Mammalian CHDs include nine members (CHD1 to CHD9), grouped into subfamilies according to the presence of specific functional domains, generally highly conserved in evolutionary terms. Mutations affecting these domains hold great potential to disrupt protein function, leading to meaningful pathogenic scenarios, such as embryonic defects incompatible with life. Here, we analysed the evolution of CHD proteins by performing a comparative study of the functional domains of CHD proteins between orthologous and paralogous protein sequences. Our findings show that the highest degree of inter-species conservation was observed at Group II (CHD3, CHD4, and CHD5) and that most of the pathological variations documented in humans involve amino acid residues that are conserved not only between species but also between paralogs. The parallel analysis of both orthologous and paralogous proteins, in cases where gene duplications have occurred, provided extra information showing patterns of flexibility as well as interchangeability between amino acid positions. This added complexity needs to be considered when the impact of novel mutations is assessed in terms of evolutionary conservation.

Keywords: chromatin remodelling; chromodomains helicase DNA-binding protein; evolutionary conservation; neurodevelopment; transcription regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cats
  • Conserved Sequence
  • DNA Helicases / chemistry
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Evolution, Molecular*
  • Humans
  • Macaca
  • Mice
  • Mutation
  • Polymorphism, Genetic*
  • Protein Domains


  • DNA-Binding Proteins
  • DNA Helicases