Pervasive coexpression of spatially proximal genes is buffered at the protein level

Abstract Genes are not randomly distributed in the genome. In humans, 10% of protein‐coding genes are transcribed from bidirectional promoters and many more are organised in larger clusters. Intriguingly, neighbouring genes are frequently coexpressed but rarely functionally related. Here we show tha...

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Main Authors: Georg Kustatscher, Piotr Grabowski, Juri Rappsilber
Format: Article
Language:English
Published: Springer Nature 2017-08-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20177548
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author Georg Kustatscher
Piotr Grabowski
Juri Rappsilber
author_facet Georg Kustatscher
Piotr Grabowski
Juri Rappsilber
author_sort Georg Kustatscher
collection DOAJ
description Abstract Genes are not randomly distributed in the genome. In humans, 10% of protein‐coding genes are transcribed from bidirectional promoters and many more are organised in larger clusters. Intriguingly, neighbouring genes are frequently coexpressed but rarely functionally related. Here we show that coexpression of bidirectional gene pairs, and closeby genes in general, is buffered at the protein level. Taking into account the 3D architecture of the genome, we find that co‐regulation of spatially close, functionally unrelated genes is pervasive at the transcriptome level, but does not extend to the proteome. We present evidence that non‐functional mRNA coexpression in human cells arises from stochastic chromatin fluctuations and direct regulatory interference between spatially close genes. Protein‐level buffering likely reflects a lack of coordination of post‐transcriptional regulation of functionally unrelated genes. Grouping human genes together along the genome sequence, or through long‐range chromosome folding, is associated with reduced expression noise. Our results support the hypothesis that the selection for noise reduction is a major driver of the evolution of genome organisation.
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spelling doaj-art-e2943f44803e47ba9a9b5bfb7009ddd72025-08-20T04:03:12ZengSpringer NatureMolecular Systems Biology1744-42922017-08-0113811410.15252/msb.20177548Pervasive coexpression of spatially proximal genes is buffered at the protein levelGeorg Kustatscher0Piotr Grabowski1Juri Rappsilber2Wellcome Trust Centre for Cell Biology, University of EdinburghChair of Bioanalytics, Institute of Biotechnology, Technische Universität BerlinWellcome Trust Centre for Cell Biology, University of EdinburghAbstract Genes are not randomly distributed in the genome. In humans, 10% of protein‐coding genes are transcribed from bidirectional promoters and many more are organised in larger clusters. Intriguingly, neighbouring genes are frequently coexpressed but rarely functionally related. Here we show that coexpression of bidirectional gene pairs, and closeby genes in general, is buffered at the protein level. Taking into account the 3D architecture of the genome, we find that co‐regulation of spatially close, functionally unrelated genes is pervasive at the transcriptome level, but does not extend to the proteome. We present evidence that non‐functional mRNA coexpression in human cells arises from stochastic chromatin fluctuations and direct regulatory interference between spatially close genes. Protein‐level buffering likely reflects a lack of coordination of post‐transcriptional regulation of functionally unrelated genes. Grouping human genes together along the genome sequence, or through long‐range chromosome folding, is associated with reduced expression noise. Our results support the hypothesis that the selection for noise reduction is a major driver of the evolution of genome organisation.https://doi.org/10.15252/msb.20177548gene expression noisegenome organisationproteomicsregulatory interferencetranscriptomics
spellingShingle Georg Kustatscher
Piotr Grabowski
Juri Rappsilber
Pervasive coexpression of spatially proximal genes is buffered at the protein level
Molecular Systems Biology
gene expression noise
genome organisation
proteomics
regulatory interference
transcriptomics
title Pervasive coexpression of spatially proximal genes is buffered at the protein level
title_full Pervasive coexpression of spatially proximal genes is buffered at the protein level
title_fullStr Pervasive coexpression of spatially proximal genes is buffered at the protein level
title_full_unstemmed Pervasive coexpression of spatially proximal genes is buffered at the protein level
title_short Pervasive coexpression of spatially proximal genes is buffered at the protein level
title_sort pervasive coexpression of spatially proximal genes is buffered at the protein level
topic gene expression noise
genome organisation
proteomics
regulatory interference
transcriptomics
url https://doi.org/10.15252/msb.20177548
work_keys_str_mv AT georgkustatscher pervasivecoexpressionofspatiallyproximalgenesisbufferedattheproteinlevel
AT piotrgrabowski pervasivecoexpressionofspatiallyproximalgenesisbufferedattheproteinlevel
AT jurirappsilber pervasivecoexpressionofspatiallyproximalgenesisbufferedattheproteinlevel