title: Clustering of protein domains in the human genome.
abstract: We present a systematic study of the clustering of genes within the human genome based on homology inferred from both sequence and structural similarity. The 3D-Genomics automated proteome annotation pipeline () was utilised to infer homology for each protein domain in the genome, for the 26 superfamilies most highly represented in the Structural Classification Of Proteins (SCOP) database. This approach enabled us to identify homologues that could not be detected by sequence-based methods alone. For each superfamily, we investigated the distribution, both within and among chromosomes, of genes encoding at least one domain within the superfamily. The results indicate a diversity of clustering behaviours: some superfamilies showed no evidence of any clustering, and others displayed significant clustering either within or among chromosomes, or both. Removal of tandem repeats reduced the levels of clustering observed, but some superfamilies still displayed highly significant clustering. Thus, our study suggests that either the process of gene duplication, or the evolution of the resulting clusters, differs between structural superfamilies.
authors.affiliation: Department of Epidemiology and Public Health, Imperial College, St Mary's Campus, London W2 1PG, UK.
authors.forename: Lianne R
authors.initials: LR
authors.lastname: Mayor
authors.forename: Keiran P
authors.initials: KP
authors.lastname: Fleming
authors.forename: Arne
authors.initials: A
authors.lastname: Müller
authors.forename: David J
authors.initials: DJ
authors.lastname: Balding
authors.forename: Michael J E
authors.initials: MJ
authors.lastname: Sternberg
mesh_terms: D015820:Cadherins / Q000145:classification / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics; D019295:Computational Biology; D005353:Fibronectins / Q000145:classification / Q000235:genetics; D020440:Gene Duplication; D015894:Genome, Human; D023281:Genomics; D018398:Homeodomain Proteins / Q000145:classification / Q000235:genetics; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics*; D017385:Sequence Homology; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D015820:Cadherins; D005353:Fibronectins; D018398:Homeodomain Proteins