Biology subjects

Hughes, A. L.

Publications and source records attributed to Hughes, A. L..

2 recordsLinked to original sources

bioRxiv2018

Chaos Game Representation: An Alignment-Free Technique for Exploring Evolutionary Relationships of Protein Sequences

Chaos Game Representation (CGR) is an iterative mapping technique, which shows patterns in amino acids or nucleotide sequences. Here we present a method for using CGR to explore evolutionary relationships of protein sequences based on amino acid properties and illustrate the approach with complete sets of protein translations from viral genomes. In an analysis of complete polyprotein sequences from the viral family Flaviviridae, the CGR method was able to cluster members of major viral groups together, but relations within groups were not well resolved in comparison to an alignment-based phylogeny. We applied the method to members of five different families of ssRNA positive-strand viruses, and each family formed a distinct cluster. We also present a method of testing the reliability of clustering in CGR-based trees, which involves the use of multiple random starting points for the CGR process.

evolutionary biology↗

bioRxiv2016

Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes.

The yeast Chd1 protein acts to position nucleosomes across genomes. Here we model the structure of the Chd1 protein in solution and when bound to nucleosomes. In the apo state the DNA binding domain contacts the edge of the nucleosome while in the presence of the non-hydrolyzable ATP analog, ADP-beryllium fluoride, we observe additional interactions between the ATPase domain and the adjacent DNA gyre 1.5 helical turns from the dyad axis of symmetry. Binding in this conformation involves unravelling the outer turn of nucleosomal DNA and requires substantial reorientation of the DNA binding domain with respect to the ATPase domains. The orientation of the DNA-binding domain is mediated by sequences in the N-terminus and mutations to this part of the protein have positive and negative effects on Chd1 activity. These observations indicate that the unfavourable alignment of C-terminal DNA binding region in solution contributes to an auto-inhibited state.

molecular biology↗