Comparing the evolutionary conservation between human essential genes, human orthologs of mouse essential genes and human housekeeping genes

Lv, Wenhua; Zheng, Jiajia; Luan, Meiwei; Shi, Miao; Zhu, Hongjie; Zhang, Mingming; Lv, Hongchao; Shang, Zhenwei; Duan, Lian; Zhang, Ruijie; Jiang, Yongshuai

doi:10.1093/bib/bbv025

Cited by 16 publications

(19 citation statements)

References 29 publications

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“…A plausible explanation is that since HKs are expressed in all tissues and are relevant for cell survival, mutations in HKs would be evolutionarily selected out. In accordance with this result, it is already known that HKs are more evolutionarily conserved than tissue specific [29, 30].…”

Section: Discussionsupporting

confidence: 81%

The distributions of protein coding genes within chromatin domains in relation to human disease

Muro

Ibn-Salem

Andrade‐Navarro

2019

Epigenetics & Chromatin

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BackgroundOur understanding of the nuclear chromatin structure has increased hugely during the last years mainly as a consequence of the advances in chromatin conformation capture methods like Hi-C. The unprecedented resolution of genome-wide interaction maps shows functional consequences that extend the initial thought of an efficient DNA packaging mechanism: gene regulation, DNA repair, chromosomal translocations and evolutionary rearrangements seem to be only the peak of the iceberg. One key concept emerging from this research is the topologically associating domains (TADs) whose functional role in gene regulation and their association with disease is not fully untangled.ResultsWe report that the lower the number of protein coding genes inside TADs, the higher the tendency of those genes to be associated with disease (p-value = 4 × ). Moreover, housekeeping genes are less associated with disease than other genes. Accordingly, they are depleted in TADs containing less than three protein coding genes (p-value = 3.9 × ). We observed that TADs with higher ratios of enhancers versus genes contained higher numbers of disease-associated genes. We interpret these results as an indication that sharing enhancers among genes reduces their involvement in disease. Larger TADs would have more chances to accommodate many genes and select for enhancer sharing along evolution.ConclusionsGenes associated with human disease do not distribute randomly over the TADs. Our observations suggest general rules that confer functional stability to TADs, adding more evidence to the role of TADs as regulatory units.

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Section: Discussionsupporting

confidence: 81%

The distributions of protein coding genes within chromatin domains in relation to human disease

Muro

Ibn-Salem

Andrade‐Navarro

2019

Epigenetics & Chromatin

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“…Ideal housekeeping genes or proteins used as internal controls must be expressed constitutively, ubiquitously, and uniformly in cells and tissue, and are not likely to be regulated by any experimental treatment (Tunbridge et al, 2011; Lv et al, 2015). Some recent studies reported that the expressions of several typical internal controls were not stable with the stimulation by pharmacological agents or under special physiological and pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

β-Actin: Not a Suitable Internal Control of Hepatic Fibrosis Caused by Schistosoma japonicum

Zhang

Liu

et al. 2019

Front. Microbiol.

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Schistosomiasis japonica is a significant health problem that leads to morbidity and mortality of humans. It is characterized by hepatic granulomatous response and fibrosis caused by eggs deposition in the liver. β-actin, a traditional housekeeping gene, is widely used as an internal control to normalize gene and protein expression. However, β-actin expression can fluctuate upon the treatment with pharmacological agents or under some physiological and pathological conditions. In this study, we found that the expressions of both β-actin mRNA and protein increased significantly with hepatic fibrosis formation after 6 weeks infection with Schistosoma japonicum and kept high level during the progression of hepatic fibrosis, while the levels of β-Tubulin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) remained stable. The dynamic change of β-actin was similar with the profibrogenic factors, including α-SMA, Collagen I, and Collagen III. We employed immunofluorescence staining and further showed that the expression level of β-actin was positively correlated with α-SMA. What is more, there was a positive correlation between the level of β-actin mRNA and the content of hydroxyproline in liver. This study provides evidences that β-actin is variable and unsatisfied for application as an internal control in hepatic fibrosis induced by S. japonicum infection.

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“…Unusual patterns in genetic sequence phylogenies suggest dynamic and relatively recent changes in the evolution of such sequences, implying evolutionarily recent patterns in the way the corresponding HDACs are regulated [49]. In fact, promoter conservation among vertebrate species seems to be more prominent for the ubiquitously expressed HDACs, particularly for HDACs 1 and 2, suggesting that these have not undergone recent evolution, a hypothesis in line with literature on the evolution of so-called “housekeeping” and “essential” genes [50]. Those HDACs that exhibit an unusual pattern of TFBSs on their promoters seem to also have a propensity for expression in fewer tissues such as seen in our results of HDAC5 and their possible preferential association with the cardiovascular/hematopoietic, muscular, nervous and endocrine tissues (Table 2).…”

Section: Discussionmentioning

confidence: 62%

Promoter conservation in HDACs points to functional implications

2019

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Background Histone deacetylases (HDACs) are the proteins responsible for removing the acetyl group from lysine residues of core histones in chromosomes, a crucial component of gene regulation. Eleven known HDACs exist in humans and most other vertebrates. While the basic function of HDACs has been well characterized and new discoveries are still being made, the transcriptional regulation of their corresponding genes is still poorly understood. Results Here, we conducted a computational analysis of the eleven HDAC promoter sequences in 25 vertebrate species to determine whether transcription factor binding sites (TFBSs) are conserved in HDAC evolution, and if so, whether they provide useful information about HDAC expression and function. Furthermore, we used tissue-specific information of transcription factors to investigate the potential expression patterns of HDACs in different human tissues based on their transcription factor binding sites. We found that the TFBS profiles of most of the HDACs were well conserved in closely related species for all HDAC promoters except HDAC7 and HDAC10. HDAC5 had particularly strong conservation across over half of the species studied, with nearly identical profiles in the primate species. Our comparisons of TFBSs with the tissue specific gene expression profiles of their corresponding TFs showed that most HDACs had the ability to be ubiquitously expressed. A few HDAC promoters exhibited the potential for preferential expression in certain tissues, most notably HDAC11 in gall bladder, while HDAC9 seemed to have less propensity for expression in the nervous system. Conclusions In general, we found evolutionary conservation in HDAC promoters that seems to be more prominent for the ubiquitously expressed HDACs. In turn, when conservation did not follow usual phylogeny, human TFBS patterns indicated possible functional relevance. While we found that HDACs appear to uniformly expressed, we confirm that the functional differences in HDACs may be less a matter of location of activity than a question of which proteins and which acetyl groups they may be acting on. Electronic supplementary material The online version of this article (10.1186/s12864-019-5973-x) contains supplementary material, which is available to authorized users.

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Comparing the evolutionary conservation between human essential genes, human orthologs of mouse essential genes and human housekeeping genes

Cited by 16 publications

References 29 publications

The distributions of protein coding genes within chromatin domains in relation to human disease

The distributions of protein coding genes within chromatin domains in relation to human disease

β-Actin: Not a Suitable Internal Control of Hepatic Fibrosis Caused by Schistosoma japonicum

Promoter conservation in HDACs points to functional implications

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