Gene Clustering in Eukaryotes


Recent advances in genomics have provided us with better understanding of genomes from many different species, their architectures and evolutionary relationships. Genome architecture (a nonrandom arrangement of functional elements in the genome, such as genes and regulatory regions) is different in eukaryotes than in prokaryotes. Although in prokaryotes, many genes are organised into linearly positioned cotranscribed groups (operons), eukaryotic genomes possess very small number of genes organised into operons. The acquisition of the nuclear membrane, decoupling of transcription and translation and adoption of the ribosome‐scanning mechanism for translation initiation (necessitating monocistronic messenger ribonucleic acids (mRNAs)) are possible reasons for the loss of operon structure in eukaryotes. Despite the general trend of low level of gene clustering within operon structures in eukaryotes, there is an evidence for nonrandom linear and spatial organisation of eukaryotic genomes, as a result of multiple mechanisms that can lead to the proximity of coexpressed genes.

Key Concepts:

  • Albeit not as common as the gene clustering within operons observed in bacteria, linear gene clustering does occur in eukaryotes.

  • In eukaryotes, linear gene clusters form predominantly by partially adaptive, but largely neutral processes, such as genome rearrangements.

  • In natal clusters, genes occupy adjacent positions on chromosomes as a result of a tandem duplication and consequent divergence.

  • In embedded clusters, coding sequence of one gene may be entirely positioned within an intron of another gene, or one gene may have exons that interweave with the exons of other genes.

  • In coregulated clusters, genes could be either linearly clustered on chromosomes to share regulatory sequences, or genes could be spatially colocalised within the nucleus forming transcription factories.

  • Linearly coregulated clusters in eukaryotes include: alternatively spliced transcripts, polycistronic messages, uORFs and genes regulated by bidirectional promoters.

  • Spatial sequestration of genes positioned distantly on the same chromosome or even on different chromosomes can modulate coregulated gene expression.

Keywords: linear gene clustering; spatial gene clustering; gene duplication; operons; polycistronic messages; trans‐splicing

Figure 1.

Examples of possible mechanisms that lead to gene clustering in eukaryotes. (a) Tandem duplication due to an unequal crossingover results in duplication of gene B and formation of gene B' that may aquire a new function. (b) Genome reduction may result in removal of large segment of , which may position genes A and B proximaly and under the control of the same promoter and regulatory elements. (c) An example of a selectively advanatageous cluster in prokaryotes. (d) An example of a spatial cluster; genes A and B are positioned distantly on the chromosome I, while genes C and D are positioned on chromosomes II and III. All of these genes are specially clustered in the nucleus.

Figure 2.

Examples of gene clustering in eukaryotes. (a) Organisation of the α‐ and β‐globin gene clusters on human chromosomes 16 and 11. Boxes represent gene locations. (b) Organisation of the Drosophila gene sina within the intron of Rh4; boxes represent exons, and introns are depicted as angled segments between exons. (c) Organisation of the cha‐1 and unc‐17 loci in Caenorhabditis elegans. Here, the first exon (SL1) is shared between the two transcripts; exon map after Alfonso et al. © Elsevier. (d) Organisation of the LASS1 and GDF1 loci in humans; transcript map after Lee © National Academy of Sciences, USA. (e) Organisation of CPA1 and its uORF controller in Saccharomyces cerevisiae. (f) Organisation of RanBP1 and Htf9‐c bidirectional genes located on murine chromosome 16. Reproduced from Guarguaglini et al.. © Portland Press Limited. (g) A generalised model for trans‐splicing in nematodes. The leader exon SL1, containing a CAP (5′ mRNA cap), is trans‐spliced onto the 5′ end of a polycistronic message, whereas the CAP‐containing SL2 leader is trans‐spliced into internal sites to generate multiple, mature mRNAs.



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Web Links

Growth differentiation factor 1 (GDF1); GeneID: 2657. GeneLink:

Growth differentiation factor 1 (GDF1); MIM number: 602880. OMIM:

LAG1 longevity assurance homolog 1 (LASS1); GeneID: 10715. GeneLink:

LAG1 longevity assurance homolog 1 (LASS1); MIM number: 606919. OMIM:

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Tarailo‐Graovac, Maja, and Chen, Nansheng(Oct 2013) Gene Clustering in Eukaryotes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006117.pub3]