What are housekeeping genes?

The concept of "housekeeping gene" has been used for four decades but remains loosely defined. Housekeeping genes are commonly described as "essential for cellular existence regardless of their specific function in the tissue or organism", and "stably expressed irrespective...

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Main Authors: Chintan J Joshi, Wenfan Ke, Anna Drangowska-Way, Eyleen J O'Rourke, Nathan E Lewis
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-07-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1010295
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author Chintan J Joshi
Wenfan Ke
Anna Drangowska-Way
Eyleen J O'Rourke
Nathan E Lewis
author_facet Chintan J Joshi
Wenfan Ke
Anna Drangowska-Way
Eyleen J O'Rourke
Nathan E Lewis
author_sort Chintan J Joshi
collection DOAJ
description The concept of "housekeeping gene" has been used for four decades but remains loosely defined. Housekeeping genes are commonly described as "essential for cellular existence regardless of their specific function in the tissue or organism", and "stably expressed irrespective of tissue type, developmental stage, cell cycle state, or external signal". However, experimental support for the tenet that gene essentiality is linked to stable expression across cell types, conditions, and organisms has been limited. Here we use genome-scale functional genomic screens together with bulk and single-cell sequencing technologies to test this link and optimize a quantitative and experimentally validated definition of housekeeping gene. Using the optimized definition, we identify, characterize, and provide as resources, housekeeping gene lists extracted from several human datasets, and 10 other animal species that include primates, chicken, and C. elegans. We find that stably expressed genes are not necessarily essential, and that the individual genes that are essential and stably expressed can considerably differ across organisms; yet the pathways enriched among these genes are conserved. Further, the level of conservation of housekeeping genes across the analyzed organisms captures their taxonomic groups, showing evolutionary relevance for our definition. Therefore, we present a quantitative and experimentally supported definition of housekeeping genes that can contribute to better understanding of their unique biological and evolutionary characteristics.
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spelling doaj.art-427b3e577d694634be26acfd89426dff2022-12-22T04:01:07ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-07-01187e101029510.1371/journal.pcbi.1010295What are housekeeping genes?Chintan J JoshiWenfan KeAnna Drangowska-WayEyleen J O'RourkeNathan E LewisThe concept of "housekeeping gene" has been used for four decades but remains loosely defined. Housekeeping genes are commonly described as "essential for cellular existence regardless of their specific function in the tissue or organism", and "stably expressed irrespective of tissue type, developmental stage, cell cycle state, or external signal". However, experimental support for the tenet that gene essentiality is linked to stable expression across cell types, conditions, and organisms has been limited. Here we use genome-scale functional genomic screens together with bulk and single-cell sequencing technologies to test this link and optimize a quantitative and experimentally validated definition of housekeeping gene. Using the optimized definition, we identify, characterize, and provide as resources, housekeeping gene lists extracted from several human datasets, and 10 other animal species that include primates, chicken, and C. elegans. We find that stably expressed genes are not necessarily essential, and that the individual genes that are essential and stably expressed can considerably differ across organisms; yet the pathways enriched among these genes are conserved. Further, the level of conservation of housekeeping genes across the analyzed organisms captures their taxonomic groups, showing evolutionary relevance for our definition. Therefore, we present a quantitative and experimentally supported definition of housekeeping genes that can contribute to better understanding of their unique biological and evolutionary characteristics.https://doi.org/10.1371/journal.pcbi.1010295
spellingShingle Chintan J Joshi
Wenfan Ke
Anna Drangowska-Way
Eyleen J O'Rourke
Nathan E Lewis
What are housekeeping genes?
PLoS Computational Biology
title What are housekeeping genes?
title_full What are housekeeping genes?
title_fullStr What are housekeeping genes?
title_full_unstemmed What are housekeeping genes?
title_short What are housekeeping genes?
title_sort what are housekeeping genes
url https://doi.org/10.1371/journal.pcbi.1010295
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