title: Three Dimensional Organization of Genome Might Have Guided the Dynamics of Gene Order Evolution in Eukaryotes.
abstract: In eukaryotes, genes are nonrandomly organized into short gene-dense regions or "gene-clusters" interspersed by long gene-poor regions. How these gene-clusters have evolved is not entirely clear. Gene duplication may not account for all the gene-clusters since the genes in most of the clusters do not exhibit significant sequence similarity. In this study, using genome-wide data sets from budding yeast, fruit-fly, and human, we show that: 1) long-range evolutionary repositioning of genes strongly associate with their spatial proximity in the nucleus; 2) presence of evolutionary DNA break-points at involved loci hints at their susceptibility to undergo long-range genomic rearrangements; and 3) correlated epigenetic and transcriptional states of engaged genes highlight the underlying evolutionary constraints. The significance of observation 1, 2, and 3 are particularly stronger for the instances of inferred evolutionary gain, as compared with loss, of linear gene-clustering. These observations suggest that the long-range genomic rearrangements guided through 3D genome organization might have contributed to the evolution of gene order. We further hypothesize that the evolution of linear gene-clusters in eukaryotic genomes might have been mediated through spatial interactions among distant loci in order to optimize co-ordinated regulation of genes. We model this hypothesis through a heuristic model of gene-order evolution.
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research (IISER)-Mohali, SAS Nagar 140306, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Bagadia
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research (IISER)-Mohali, SAS Nagar 140306, India.
authors.forename: Arashdeep
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research (IISER)-Mohali, SAS Nagar 140306, India sandhuks@iisermohali.ac.in.
authors.forename: Kuljeet
authors.initials: K
authors.lastname: Singh Sandhu
mesh_terms: D056890:Eukaryota / Q000235:genetics*; D019143:Evolution, Molecular; D023061:Gene Order / Q000235:genetics; D016678:Genome; D023281:Genomics; D006801:Humans; D005810:Multigene Family / Q000235:genetics*
keywords: chromatin interactions; gene-clusters; genome organization; genomic rearrangements