Genes lost during the transition from land to water in cetaceans highlight genomic changes involved in aquatic adaptations

AbstractThe transition from land to water in whales and dolphins (cetaceans) was accompanied by remarkable anatomical, physiological and behavioral adaptations. To better understand the genomic changes that occurred during this transition, we systematically screened for protein-coding genes that were inactivated in the ancestral cetacean lineage. We discovered genes whose loss is likely beneficial for cetaceans by reducing the risk of thrombus formation during diving (F12, KLKB1), improving the fidelity of oxidative DNA damage repair (POLM), and protecting from oxidative stress-induced lung inflammation (MAP3K19). Additional gene losses may reflect other diving-related adaptations, such as enhanced vasoconstriction during the diving response (mediated by SLC6A18) and altered pulmonary surfactant composition (SEC14L3), while loss of SLC4A9 relates to a reduced need for saliva in aquatic environments. Finally, the complete loss of melatonin synthesis and receptor genes (AANAT, ASMT, MTNR1A/B) may have been a precondition for the evolution of unihemispheric sleep. Our findings suggest that some genes lost in the ancestral cetacean lineage may have been involved in adapting to a fully-aquatic lifestyle.

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Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations

Science Advances ◽

10.1126/sciadv.aaw6671 ◽

2019 ◽

Vol 5 (9) ◽

pp. eaaw6671 ◽

Cited By ~ 25

Author(s):

Matthias Huelsmann ◽

Nikolai Hecker ◽

Mark S. Springer ◽

John Gatesy ◽

Virag Sharma ◽

...

Keyword(s):

Pulmonary Surfactant ◽

Thrombus Formation ◽

Diving Response ◽

Protein Coding ◽

Genomic Changes ◽

Protein Coding Genes ◽

Unihemispheric Sleep ◽

Damage Repair ◽

Surfactant Composition ◽

And Oxidative Stress

The transition from land to water in whales and dolphins (cetaceans) was accompanied by remarkable adaptations. To reveal genomic changes that occurred during this transition, we screened for protein-coding genes that were inactivated in the ancestral cetacean lineage. We found 85 gene losses. Some of these were likely beneficial for cetaceans, for example, by reducing the risk of thrombus formation during diving (F12 and KLKB1), erroneous DNA damage repair (POLM), and oxidative stress–induced lung inflammation (MAP3K19). Additional gene losses may reflect other diving-related adaptations, such as enhanced vasoconstriction during the diving response (mediated by SLC6A18) and altered pulmonary surfactant composition (SEC14L3), while loss of SLC4A9 relates to a reduced need for saliva. Last, loss of melatonin synthesis and receptor genes (AANAT, ASMT, and MTNR1A/B) may have been a precondition for adopting unihemispheric sleep. Our findings suggest that some genes lost in ancestral cetaceans were likely involved in adapting to a fully aquatic lifestyle.

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Transcriptome profiling reveals the endogenous sponging role of LINC00659 and UST-AS1 in high altitude induced thrombosis

Thrombosis and Haemostasis ◽

10.1055/a-1390-1713 ◽

2021 ◽

Author(s):

Prabhash Kumar Jha ◽

Aatira Vijay ◽

Amit Prabhakar ◽

Tathagata Chatterjee ◽

Velu Nair ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

High Altitude ◽

Expression Profile ◽

Thrombus Formation ◽

Pearson Correlation ◽

Coagulation Cascade ◽

Protein Coding ◽

Vein Thrombosis ◽

Protein Coding Genes ◽

Deep Vein

Background: The pathophysiology of Deep vein thrombosis (DVT) is considered as multifactorial, where thrombus formation is interplay of genetic and acquired risk factors. A little is known about the expression profile and roles of lncRNAs in human subjects developing DVT at high altitude. Methods: Using RNAseq, we compared peripheral blood mRNA and lncRNA expression profile in human High Altitude deep Vein Thrombosis (HA-DVT) patients with high altitude control subjects. We used DESeq to identify differentially expressed (DE) genes. We annotated the long noncoding RNAs using NONCODE 3.0 database. In silico putative lncRNA-miRNA association study unravels the endogenous miRNA sponge associated with our candidate lncRNAs. These findings were validated by siRNA knockdown assay of the candidate lncRNAs conducted in primary endothelial cells. Results: We identified 1524 DE mRNA and 973 DE lncRNAs. Co-expressed protein-coding genes analysis resulted in a list of 722 coexpressed protein-coding genes with a Pearson correlation coefficients >0.7. The functional annotation of co-expressed genes and putative proteins revealed their involvement in the hypoxia, immune response and coagulation cascade. Through its miRNA response elements (MREs) to compete for miR-143 and miR-15, lncRNA-LINC00659 and UXT-AS1 regulates the expression of prothrombotic genes. Furthermore, in vitro RNA interference (siRNA) simultaneously suppressed lncRNAs and target gene mRNA level. Conclusions: This transcriptome profile describes novel potential mechanisms of interaction between lncRNAs, the coding genes, miRNAs and regulatory transcription factors that define the thrombotic signature and may be used in establishing lncRNAs as biomarker in HA-DVT.

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A Mechanistic Overview of Spinal Cord Injury, Oxidative DNA Damage Repair and Neuroprotective Therapies

International Journal of Neuroscience ◽

10.1080/00207454.2021.1912040 ◽

2021 ◽

pp. 1-25

Author(s):

Jaspreet Kaur ◽

Aditya Mojumdar

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Dna Damage Repair ◽

Damage Repair ◽

Cord Injury ◽

Neuroprotective Therapies

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Phosphoglycolate has profound metabolic effects but most likely no role in a metabolic DNA response in cancer cell lines

Biochemical Journal ◽

10.1042/bcj20180435 ◽

2019 ◽

Vol 476 (4) ◽

pp. 629-643 ◽

Cited By ~ 1

Author(s):

Isabelle Gerin ◽

Marina Bury ◽

Francesca Baldin ◽

Julie Graff ◽

Emile Van Schaftingen ◽

...

Keyword(s):

Dna Damage ◽

Cell Lines ◽

Oxidative Dna Damage ◽

Fold Increase ◽

Metabolic Effects ◽

Phosphoglycerate Mutase ◽

Wild Type ◽

Metabolic Disturbances ◽

Phosphoglycolate Phosphatase ◽

Damage Repair

Abstract Repair of a certain type of oxidative DNA damage leads to the release of phosphoglycolate, which is an inhibitor of triose phosphate isomerase and is predicted to indirectly inhibit phosphoglycerate mutase activity. Thus, we hypothesized that phosphoglycolate might play a role in a metabolic DNA damage response. Here, we determined how phosphoglycolate is formed in cells, elucidated its effects on cellular metabolism and tested whether DNA damage repair might release sufficient phosphoglycolate to provoke metabolic effects. Phosphoglycolate concentrations were below 5 µM in wild-type U2OS and HCT116 cells and remained unchanged when we inactivated phosphoglycolate phosphatase (PGP), the enzyme that is believed to dephosphorylate phosphoglycolate. Treatment of PGP knockout cell lines with glycolate caused an up to 500-fold increase in phosphoglycolate concentrations, which resulted largely from a side activity of pyruvate kinase. This increase was much higher than in glycolate-treated wild-type cells and was accompanied by metabolite changes consistent with an inhibition of phosphoglycerate mutase, most likely due to the removal of the priming phosphorylation of this enzyme. Surprisingly, we found that phosphoglycolate also inhibits succinate dehydrogenase with a Ki value of <10 µM. Thus, phosphoglycolate can lead to profound metabolic disturbances. In contrast, phosphoglycolate concentrations were not significantly changed when we treated PGP knockout cells with Bleomycin or ionizing radiation, which are known to lead to the release of phosphoglycolate by causing DNA damage. Thus, phosphoglycolate concentrations due to DNA damage are too low to cause major metabolic changes in HCT116 and U2OS cells.

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Adaptation, Ecology, and Evolution of the Halophilic Stromatolite ArchaeonHalococcus hamelinensisInferred through Genome Analyses

Archaea ◽

10.1155/2015/241608 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Reema K. Gudhka ◽

Brett A. Neilan ◽

Brendan P. Burns

Keyword(s):

Unknown Function ◽

Energy Production ◽

Extreme Environment ◽

Evolutionary Significance ◽

Base Pairs ◽

Protein Coding ◽

Inorganic Ion ◽

Damage Repair ◽

Genome Analyses

Halococcus hamelinensiswas the first archaeon isolated from stromatolites. These geomicrobial ecosystems are thought to be some of the earliest known on Earth, yet, despite their evolutionary significance, the role of Archaea in these systems is still not well understood. Detailed here is the genome sequencing and analysis of an archaeon isolated from stromatolites. The genome ofH. hamelinensisconsisted of 3,133,046 base pairs with an average G+C content of 60.08% and contained 3,150 predicted coding sequences or ORFs, 2,196 (68.67%) of which were protein-coding genes with functional assignments and 954 (29.83%) of which were of unknown function. Codon usage of theH. hamelinensisgenome was consistent with a highly acidic proteome, a major adaptive mechanism towards high salinity. Amino acid transport and metabolism, inorganic ion transport and metabolism, energy production and conversion, ribosomal structure, and unknown function COG genes were overrepresented. The genome ofH. hamelinensisalso revealed characteristics reflecting its survival in its extreme environment, including putative genes/pathways involved in osmoprotection, oxidative stress response, and UV damage repair. Finally, genome analyses indicated the presence of putative transposases as well as positive matches of genes ofH. hamelinensisagainst various genomes of Bacteria, Archaea, and viruses, suggesting the potential for horizontal gene transfer.

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Mechanism of oxidative DNA damage repair and relevance to human pathology

Mutation Research/Reviews in Mutation Research ◽

10.1016/j.mrrev.2007.10.003 ◽

2008 ◽

Vol 659 (1-2) ◽

pp. 4-14 ◽

Cited By ~ 66

Author(s):

M DERRICO ◽

E PARLANTI ◽

E DOGLIOTTI

Keyword(s):

Dna Damage ◽

Oxidative Dna Damage ◽

Dna Damage Repair ◽

Damage Repair ◽

Human Pathology

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Interplay between miRNAs and host genes and their role in cancer

Briefings in Functional Genomics ◽

10.1093/bfgp/elz002 ◽

2019 ◽

Vol 18 (4) ◽

pp. 255-266 ◽

Cited By ~ 16

Author(s):

Baohong Liu ◽

Yu Shyr ◽

Jianping Cai ◽

Qi Liu

Keyword(s):

Tumor Suppressors ◽

Target Genes ◽

Epithelial Mesenchymal Transition ◽

Fine Tuning ◽

Data Sets ◽

Protein Coding ◽

Mesenchymal Transition ◽

Damage Repair ◽

Cancer Types ◽

Host Genes

Abstract MicroRNAs (miRNAs) are small endogenous non-coding functional RNAs that post-transcriptionally regulate gene expression. They play essential roles in nearly all biological processes including cell development and differentiation, DNA damage repair, cell death as well as intercellular communication. They are highly involved in cancer, acting as tumor suppressors and/or promoters to modulate cell proliferation, epithelial-mesenchymal transition and tumor invasion and metastasis. Recent studies have shown that more than half of miRNAs are located within protein-coding or non-coding genes. Intragenic miRNAs and their host genes either share the promoter or have independent transcription. Meanwhile, miRNAs work as partners or antagonists of their host genes by fine-tuning their target genes functionally associated with host genes. This review outlined the complicated relationship between intragenic miRNAs and host genes. Focusing on miRNAs known as oncogenes or tumor suppressors in specific cancer types, it studied co-expression relationships between these miRNAs and host genes in the cancer types using TCGA data sets, which validated previous findings and revealed common, tumor-specific and even subtype-specific patterns. These observations will help understand the function of intragenic miRNAs and further develop miRNA therapeutics in cancer.

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