Functional gene groups are concentrated within chromosomes, among chromosomes and in the nuclear space of the human genome
Open accessAbstract
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.
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Genetic architecture of Alzheimer's disease
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“Interestingly, there is evidence that groups of genes close together in chromosomal space function in similar biological pathways (Thevenin et al., 2014), suggesting this approach may be valid to identify overall pathways and functions perturbed by GWAS variants, although the specific genes investigated may not be dir…”
Background
- Authors
- Thévenin, A., Ein-Dor, L., Ozery-Flato, M., & Shamir, R.
- Affiliations
- Bielefeld University (DE)
- Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel
- Tel Aviv University (IL)
- IBM Research—Haifa, Mount Carmel, Haifa 3498825, Israel
- ORCID
- Ozery-Flato, Michal
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07-23
- Volume
- 42
- Issue
- 15
- Pages
- 9854-9861
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4150778
- OpenAlex
- W2097444625
- Cited by
- 84
- References
- 48
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 10 · 2020: 7 · 2019: 10 · 2018: 11 · 2017: 11 · 2016: 5 · 2015: 11 · 2014: 1
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- University of Pennsylvania
- University of Missouri
- Tel Aviv University
- Universität Bielefeld
- Israeli Centers for Research Excellence (41/11)
- Planning and Budgeting Committee of the Council for Higher Education of Israel (41/11)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- human genome organization, chromosome organization, 3D nuclear architecture, Hi-C contact maps, protein complexes, biological pathways, genetic colocalization, gene duplication, chromosomal rearrangements
- MeSH terms
- Cell Nucleus, Chromosomes, Human, Genes, Humans, Genome, Human, Protein Interaction Mapping, Intranuclear Space
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