Functional gene groups are concentrated within chromosomes, among chromosomes and in the nuclear space of the human genome.

Annelyse Thévenin,Liat Ein-Dor,Ron Shamir,Michal Ozery-Flato

doi:10.1093/nar/gku667

Annelyse Thévenin, Liat Ein-Dor + Show 2 more

Open Access

https://doi.org/10.1093/nar/gku667

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Abstract

Genomes undergo changes in organization as a result of gene duplications, chromosomal rearrangements and local mutations, among other mechanisms. In contrast to prokaryotes, in which genes of a common function are often organized in operons and reside contiguously along the genome, most eukaryotes show much weaker clustering of genes by function, except for few concrete functional groups. We set out to check systematically if there is a relation between gene function and gene organization in the human genome. We test this question for three types of functional groups: pairs of interacting proteins, complexes and pathways. We find a significant concentration of functional groups both in terms of their distance within the same chromosome and in terms of their dispersal over several chromosomes. Moreover, using Hi-C contact map of the tendency of chromosomal segments to appear close in the 3D space of the nucleus, we show that members of the same functional group that reside on distinct chromosomes tend to co-localize in space. The result holds for all three types of functional groups that we tested. Hence, the human genome shows substantial concentration of functional groups within chromosomes and across chromosomes in space.

Highlights

Cellular processes involve multiple types of functional relations between genes, including protein–protein interactions, regulatory relations and co-expression
Hershberg et al used network analysis methods to show that adjacent genes are often co-regulated by the same transcription factor (TF) [5]
We develop a general methodology for analyzing the connection between functional gene groups and the linear and spatial arrangement of genes in the human genome

Summary

INTRODUCTION

Cellular processes involve multiple types of functional relations between genes, including protein–protein interactions, regulatory relations and co-expression. The aforementioned studies along with a handful of others indicate that there is a link between the relative genomic position of genes and their functional relations, though the eukaryotic clusters are usually much less compact than their prokaryotic counterparts [13]. This relatively weaker clustering effect may imply that a more complex mechanism underlies gene arrangement in eukaryotes, incorporating a diversity of influences from multiple types of functional relations. We develop a general methodology for analyzing the connection between functional gene groups and the linear and spatial arrangement of genes in the human genome. Our findings show that functionally related genes tend to co-localize and manifest clustered organization within and across the chromosomes on all three levels

MATERIALS AND METHODS

Statistical Methodology

RESULTS

DISCUSSION