Orientation, distance, regulation and function of neighbouring genes.
The sequencing of the human genome has allowed us to observe globally and in detail the arrangement of genes along the chromosomes. There are multiple lines of evidence that this arrangement is not random, both in terms of intergenic distances and orientation of neighbouring genes. We have undertaken a systematic evaluation of the spatial distribution and orientation of known genes across the human genome. We used genome-level information, including phylogenetic conservation, single nucleotide polymorphism density and correlation of gene expression to assess the importance of this distribution. In addition to confirming and extending known properties of the genome, such as the significance of gene deserts and the importance of 'head to head' orientation of gene pairs in proximity, we provide significant new observations that include a smaller average size for intervals separating the 3' ends of neighbouring genes, a correlation of gene expression across tissues for genes as far as 100 kilobases apart and signatures of increasing positive selection with decreasing interval size surprisingly relaxing for intervals smaller than approximately 500 base pairs. Further, we provide extensive graphical representations of the genome-wide data to allow for observations and comparisons beyond what we address.
Gherman
Adrian
A
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Wang
Ruihua
R
Avramopoulos
Dimitrios
D
D001665:Binding Sites; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D019295:Computational Biology; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D023061:Gene Order; D015894:Genome, Human; D006801:Humans; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics
D014157:Transcription Factors