What are housekeeping genes?
What are housekeeping genes?
复制标题
DOI：
10.1371/journal.pcbi.1010295
复制
发表时间：
2022-07
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
作者：
“管家基因”的概念已经被使用了40年，但定义仍然很松散。管家基因通常被描述为“无论其在组织或有机体中的特定功能如何，都是细胞存在所必需的”，并且“无论组织类型、发育阶段、细胞周期状态或外部信号如何，都能稳定表达”。然而，对于基因的重要性与细胞类型、条件和生物体的稳定表达有关这一原则的实验支持是有限的。在这里，我们使用基因组规模的功能基因组筛选以及大量和单细胞测序技术来测试这种联系，并优化定量和实验验证的管家基因定义。利用优化后的定义，我们从几个人类数据集和其他10个动物物种（包括灵长类动物、鸡和秀丽隐杆线虫）中提取了管家基因列表，并对其进行了识别、表征和提供资源。我们发现，稳定表达的基因并不一定是必需的，而且，在不同的生物体中，必需和稳定表达的单个基因可能存在很大差异；然而，在这些基因中富集的通路是保守的。此外，在所分析的生物体中，管家基因的保护水平捕获了它们的分类群，显示了我们定义的进化相关性。因此，我们提出了一个定量的和实验支持的管家基因的定义，可以有助于更好地理解其独特的生物学和进化特征。管家基因通常与四个主要的生物学标准相关联-跨样本表达的稳定性，必要性，参与细胞维护和进化保守。然而，这些标准之间的关系并没有得到太多的讨论。管家基因在转化和基础科学研究中具有广泛的兴趣。因此，为这些标准提供实验依据是很重要的。在这篇文章中，我们使用基尼系数，使用跨越11个生物体的15个转录组，比较了表达稳定性与其他三个标准。我们发现：(1)无论使用组织转录组还是癌症转录组计算，先前确定的人类管家基因的基尼系数都较低。(2)人体组织和癌细胞的低基尼系数基因富集，细胞功能差异显著。(3)与其他基因相比，人类、CHO细胞和秀丽隐杆线虫必需基因的基尼系数可能较低。(4)不同生物间保守的同源物基尼系数能够概括生物特异性信息。所有这些结果提供了一个定量的观点，管家基因跨生物体和暗示他们的进化重要性。
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. Housekeeping genes have often been associated with four main biological criteria–stability in expression across samples, essentiality, participation in cellular maintenance, and evolutionarily conserved. However, the relationship between these criteria has not been much discussed. Housekeeping genes are of broad interest for translational and basic science research. Thus, it is important to present experimental bases for these criteria. In this article, using the Gini coefficient, we compare stability of expression with the other three criteria using 15 transcriptomes spanning 11 organisms. We found that: (1) Previously identified housekeeping genes in humans had lower Gini coefficients regardless of whether they were calculated using tissue or cancer transcriptomes. (2) Genes with low Gini coefficients for human tissues and cancer cells were enriched for significantly different cellular functions. (3) Essential genes for humans, CHO cells, and C. elegans were likely to have lower Gini coefficients compared to other genes. (4) Gini coefficients of orthologs conserved across different organisms were able to recapitulate organism-specific information. All these results provide a quantitative view of housekeeping genes across organisms and hint at their evolutionary importance.
登录
查看更多内容
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1007/978-1-4939-7847-2_10
发表时间：
2018-01-01
期刊：
PHENOTYPIC SCREENING
影响因子：
--
作者：
Ke, Wenfan;Drangowska-Way, Anna;O'Rourke, Eyleen J.
通讯作者：
O'Rourke, Eyleen J.
影响因子：
56.9
作者：
Cao, Junyue;Packer, Jonathan S.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
28.2
作者：
Aguirre AJ;Meyers RM;Weir BA;Vazquez F;Zhang CZ;Ben-David U;Cook A;Ha G;Harrington WF;Doshi MB;Kost-Alimova M;Gill S;Xu H;Ali LD;Jiang G;Pantel S;Lee Y;Goodale A;Cherniack AD;Oh C;Kryukov G;Cowley GS;Garraway LA;Stegmaier K;Roberts CW;Golub TR;Meyerson M;Root DE;Tsherniak A;Hahn WC
通讯作者：
Hahn WC