Stronger selective constraint on downstream genes in the oxidative phosphorylation pathway of cetaceans

Tian, Ran; Xu, Shixia; Chai, Simin; Yin, Daiqing; Zakon, Harold H.; Yang, Guang

doi:10.1111/jeb.13213

Cited by 13 publications

(6 citation statements)

References 54 publications

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“…UQCRQ is identified as a small core-associated protein and a subunit of ubiquinol-cytochrome c reductase complex III [ 37 ]. Although no report showed that UQCRQ is directly related to NAFLD, UQCRQ is associated with oxidative phosphorylation pathway [ 38 ]. Based on the relationship between oxidative phosphorylation and NAFLD, we speculate that UQCRQ is linked to NAFLD and may be a key gene in the pathogenesis of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease

Zeng

Shi²,

Xiao³

et al. 2021

BioMed Research International

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Background. The morbidity of nonalcoholic fatty liver disease (NAFLD) has been rising, but the pathogenesis of NAFLD is still elusive. This study is aimed at determining NAFLD-related hub genes based on weighted gene coexpression network analysis (WGCNA). Methods. GSE126848 dataset based construction of coexpression networks was performed based on WGCNA. Database for Annotation, Visualization, and Integrated Discovery (DAVID) was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hub genes were identified and validated in independent datasets and mouse model. Results. We found that the steelblue module was most significantly correlated with NAFLD. Total 15 hub genes (NDUFA9, UQCRQ, NDUFB8, COPS5, RPS17, UBL5, PSMA3, PSMA1, SF3B5, MRPL27, RPL26, PDCD5, PFDN6, SNRPD2, PSMB3) were derived from both the coexpression and PPI networks and considered “true” hub genes. Functional enrichment analysis showed that the hub genes were related to NAFLD pathway and oxidative phosphorylation. Independent dataset-based analysis and the establishment of NAFLD mouse model confirmed the involvement of two hub genes NDUFA9 and UQCRQ in the pathogenesis of NAFLD. Conclusions. Oxidative phosphorylation and NAFLD pathway may be crucially involved in the pathogenesis of NAFLD, and two hub genes NDUFA9 and UQCRQ might be diagnostic biomarkers and therapeutic targets for NAFLD.

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Section: Discussionmentioning

confidence: 99%

WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease

Zeng

Shi²,

Xiao³

et al. 2021

BioMed Research International

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“…Mitochondria function to supply cellular energy and produce heat and are therefore extremely sensitive to heat and energy-related selective pressure [ 1 , 19 – 22 ]. The role of selection in the evolution of mitochondrial DNA (mtDNA) attracted little attention until recently [ 3 , 9 , 23 , 24 ]. Mitochondrial OXPHOS genes have been shown to display evidence of adaptive evolution in, for example, dogs, bats, birds and fishes [ 21 , 22 , 25 , 26 ], and numerous studies have detected signals of positive selection in mitochondrial genes [ 21 – 23 , 27 ], suggesting positive selection plays a strong potential role in adaptation [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Complete mitochondrial genomes reveal robust phylogenetic signals and evidence of positive selection in horseshoe bats

et al. 2021

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Background In genus Rhinolophus, species in the Rhinolophus philippinensis and R. macrotis groups are unique because the horseshoe bats in these group have relatively low echolocation frequencies and flight speeds compared with other horseshoe bats with similar body size. The different characteristics among bat species suggest particular evolutionary processes may have occurred in this genus. To study the adaptive evidence in the mitochondrial genomes (mitogenomes) of rhinolophids, especially the mitogenomes of the species with low echolocation frequencies, we sequenced eight mitogenomes and used them for comparative studies of molecular phylogeny and adaptive evolution. Results Phylogenetic analysis using whole mitogenome sequences produced robust results and provided phylogenetic signals that were better than those obtained using single genes. The results supported the recent establishment of the separate macrotis group. The signals of adaptive evolution discovered in the Rhinolophus species were tested for some of the codons in two genes (ND2 and ND6) that encode NADH dehydrogenases in oxidative phosphorylation system complex I. These genes have a background of widespread purifying selection. Signals of relaxed purifying selection and positive selection were found in ND2 and ND6, respectively, based on codon models and physicochemical profiles of amino acid replacements. However, no pronounced overlap was found for non-synonymous sites in the mitogenomes of all the species with low echolocation frequencies. A signal of positive selection for ND5 was found in the branch-site model when R. philippinensis was set as the foreground branch. Conclusions The mitogenomes provided robust phylogenetic signals that were much more informative than the signals obtained using single mitochondrial genes. Two mitochondrial genes that encoding proteins in the oxidative phosphorylation system showed some evidence of adaptive evolution in genus Rhinolophus and the positive selection signals were tested for ND5 in R. philippinensis. These results indicate that mitochondrial protein-coding genes were targets of adaptive evolution during the evolution of Rhinolophus species, which might have contributed to a diverse range of acoustic adaptations in this genus.

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“…QCR8 (encoded by Uqcrq) is a small core-associated protein and a subunit of ubiquinol-cytochrome c reductase complex III associated with the oxidative phosphorylation pathway. Intriguingly, Zeng et al [76] found a potential relationship with the pathogenesis of non-alcoholic steatohepatitis, although the mechanistic process remains obscure. Tian et al [77] nevertheless revealed this protein is strongly associated with hypoxia stress resistance, a point of great interest in the context of the liver metabolic changes associated with metastatic liver colonization.…”

Section: Heme Biosynthesis and Electron Transport Chainmentioning

confidence: 99%

Liver metastatic colonization by invasive cancer cells: a review of potential biomarkers with mitochondrial involvement

Pouliquen

2024

Explor Dig Dis

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The liver, characterized by a unique metabolic and immunosuppressive environment, is also the organ to which invasive malignant cells of many different cancer types most frequently metastasize. The reasons for this organ-specific metastatic process have been investigated for decades. This review first provides an overview of recent breakthroughs in this field, introducing intercellular communication between circulating tumor cells and the heterogeneous cell populations of the liver, and modifications to the extracellular matrix (ECM). Subsequently, to improve the understanding of the molecular mechanisms involved in the metastasis of colorectal cancer to the liver, the second leading cause of cancer-related mortality, the recent literature on this question was analyzed. Among the various parameters involved, the mechanisms behind the activation of hepatic stellate cells, proteins inducing ECM remodeling, specific genomic features of liver metastases, metabolic rewiring, and characteristics of stromal-enriched microenvironments were discussed. To provide more insights into the molecular determinants of liver metastatic colonization, important findings reported on a set of mitochondrial proteins were addressed, the relative abundance of which changed in the liver during the progression stage of an aggressive experimental model of peritoneal malignant mesothelioma in immunocompetent rats. Based on previous studies cross-comparing the liver proteomes from curcumin-treated tumor-bearing rats/untreated tumor-bearing rats/normal rats, data from the literature were reviewed for 25 mitochondrial proteins of interest. Their role in lipid metabolism, heme biosynthesis, the electron transport chain, small molecule transport, mitochondrial dynamics, the tricarboxylic acid cycle, and protection against oxidative stress were analyzed in the context of both cancer and non-malignant liver diseases.

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Stronger selective constraint on downstream genes in the oxidative phosphorylation pathway of cetaceans

Cited by 13 publications

References 54 publications

WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease

WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease

Complete mitochondrial genomes reveal robust phylogenetic signals and evidence of positive selection in horseshoe bats

Liver metastatic colonization by invasive cancer cells: a review of potential biomarkers with mitochondrial involvement

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