title: Intertypic modular exchanges of genomic segments by homologous recombination at universally conserved segments in human adenovirus species D.
abstract: Human adenovirus species D (HAdV-D), which is composed of clinically and epidemiologically important pathogens worldwide, contains more taxonomic "types" than any other species of the genus Mastadenovirus, although the mechanisms accounting for the high level of diversity remain to be disclosed. Recent studies of known and new types of HAdV-D have indicated that intertypic recombination between distant types contributes to the increasing diversity of the species. However, such findings raise the question as to how homologous recombination events occur between diversified types since homologous recombination is suppressed as nucleotide sequences diverge. In order to address this question, we investigated the distribution of the recombination boundaries in comparison with the landscape of intergenomic sequence conservation assessed according to the synonymous substitution rate (dS). The results revealed that specific genomic segments are conserved between even the most distantly related genomes; we call these segments "universally conserved segments" (UCSs). These findings suggest that UCSs facilitate homologous recombination, resulting in intergenomic segmental exchanges of UCS-flanking genomic regions as recombination modules. With the aid of such a mechanism, the haploid genomes of HAdV-Ds may have been reshuffled, resulting in chimeric genomes out of diversified repertoires in the HAdV-D population analogous to the MHC region reshuffled via crossing over in vertebrates. In addition, some HAdVs with chimeric genomes may have had the opportunity to avoid host immune responses thereby causing epidemics.
authors.affiliation: Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814, Japan.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gonzalez
authors.affiliation: Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814, Japan.
authors.forename: Kanako O
authors.initials: KO
authors.lastname: Koyanagi
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo 002-8072, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kitaichi
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Ophthalmology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan; Hobara Eye clinic, Date 960-0612, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Kaneko
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
authors.affiliation: Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814, Japan. Electronic address: watanabe@ist.hokudai.ac.jp.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D016679:Genome, Viral; D059765:Homologous Recombination; D010802:Phylogeny; D016415:Sequence Alignment
keywords: Adenovirus; Homologous recombination; Modular exchange; Recombination hotspot; Synonymous substitution rate