On the nature of human housekeeping genes

doi:10.1016/j.tig.2008.08.004

Trends in Genetics

Volume 24, Issue 10, October 2008, Pages 481-484

https://doi.org/10.1016/j.tig.2008.08.004 Get rights and content

Using a collection of expressed sequence tag (EST) data, we re-evaluated the correlation of tissue specificity with genomic structure, phyletic age, evolutionary rate and promoter architecture of human genes. We found that housekeeping genes are less compact and older than tissue-specific genes, and they evolve more slowly in terms of both coding and core promoter sequences. Housekeeping genes primarily use CpG-dependent core promoters, whereas the majority of tissue-specific genes possess neither CpG-islands nor TATA-boxes in their core promoters.

Section snippets

Expressed sequence tag–based evidence

Housekeeping (HK) genes are ubiquitously expressed in all tissue and cell types and constitute the basal transcriptome for the maintenance of basic cellular functions. Partitioning transcriptomes into HK and tissue-specific (TS) genes and characterizing the two groups of genes in terms of their genomic structure, phyletic age, evolutionary rate and transcriptional regulation are fundamental to understand human transcriptomes. Many studies have revealed the structural 1, 2, evolutionary 3, 4 and

Gene structure

We investigated the breath of expression for 17 288 human RefSeq loci [downloaded from NCBI (June 18, 2007 update)] across 18 human tissues (Ref. [7]; Supplementary Methods), and defined HK and TS genes as those expressed in all 18 tissues and in only 1 tissue, respectively. We observed that genes’ length parameters are positively correlated with expression breadth (Figure 1a). The medians of genomic, transcript and CDS lengths are 28.8, 2.8 and 1.4 kb for HK genes and 7.2, 1.6 and 1.0 kb for TS

Evolutionary features

The coding sequences of HK genes are thought to evolve more slowly than those of TS genes [3]. The Ka/Ks ratios, calculated from 14 961 human–mouse orthologs, are negatively correlated with expression breadth (Figure 1c), consistent with previous observations. Moreover, we observed that the sequence divergences of [−100, +100] core promoters are also negatively correlated with expression breadth (Figure 1d). The numbers of substitutions per site in HK gene promoters (median of 0.29) are

Promoter architecture

TATA-box and CpG-island are two of the most-characterized promoter features related to tissue specificity [5]. TATA-box is thought to be absent in HK genes [17], whereas CpG-island covers the transcription start sites of most HK genes [18]. We classified 16 585 (95.9% of total) human genes according to the presence and absence of CpG-island and TATA-box in the core promoter. We found that CpG+/TATA−, CpG−/TATA−, CpG−/TATA+ and CpG+/TATA+ genes constitute 58.0, 31.4, 6.7 and 3.9% of the total,

Concluding remarks

Structural and expression parameters concerning gene organization, expression rate, tissue specificity and regulation are correlated to variable extents and convey important information on gene and genome evolution 23, 24. Based on thorough analyses of the public expressed sequence tag data, we re-evaluated some of these parameters related to tissue specificity and compared them with previous results that were largely based on microarray data. We confirmed some relationships, such as the

Acknowledgements

The authors thank the anonymous reviewers for critical comments and helpful suggestions. This work was supported by the National Basic Research Program of China (2006CB910404).

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^*: These authors contributed equally to this work.

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Trends in Genetics

UpdateGenome AnalysisOn the nature of human housekeeping genes

Section snippets

Expressed sequence tag–based evidence

Gene structure

Evolutionary features

Promoter architecture

Concluding remarks

Acknowledgements

Trends Genet.

Trends Genet.

Trends Genet.

Biochem. Biophys. Res. Commun.

J. Mol. Biol.

Trends Genet.

Trends Genet.

Mammalian housekeeping genes evolve more slowly than tissue-specific genes

Mol. Biol. Evol.

Relationship between the tissue-specificity of mouse gene expression and the evolutionary origin and function of the proteins

Genome Biol.

Promoter features related to tissue specificity as measured by Shannon entropy

Genome Biol.

Housekeeping genes tend to show reduced upstream sequence conservation

Genome Biol.

How many human genes can be defined as housekeeping with current expression data?

BMC Genomics

Update
Genome Analysis
On the nature of human housekeeping genes