Giant island mice exhibit widespread gene regulatory evolution in key metabolic organs
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ABSTRACT:
PROVIDER: PRJNA557128 | ENA |
REPOSITORIES: ENA
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Project description:Background: Island populations repeatedly evolve extreme body sizes, but the genomic basis of this morphological pattern remains largely unknown. To understand how organisms on islands evolve gigantism, we compared genome-wide patterns of gene expression in Gough Island mice, the largest wild house mice in the world, and mice from the WSB/EiJ wild-derived inbred strain. In a highly replicated experiment, we used RNASeq to quantify differences in gene expression in three key metabolic organs: gonadal adipose depot, hypothalamus, and liver. Results: We discovered pervasive evidence of transcriptional evolution, with 20% or more of differentially regulated transcripts in each organ exhibiting expression fold changes of at least 2X. By considering differential expression jointly with the genomic positions of quantitative trait loci for body size and single nucleotide differences located within established tissue-specific regulatory elements, we nominated 66 candidate genes for extreme size evolution, including Irs1 and Lrp1. Patterns of differential expression across three developmental time points in the liver revealed that Arid5b potentially regulates tens of co-regulated gene groups. Functional enrichment analyses on thousands of differentially expressed genes pointed to cell cycling, mitochondrial function, signaling pathways, immune reactivity, and nutrient metabolism as potential causes of weight accumulation in Gough Island mice. Conclusion: Collectively, our results suggest that extensive regulatory evolution in metabolic organs contributed to the rapid evolution of gigantism during the short time house mice have inhabited Gough Island.
2020-09-18 | GSE135007 | GEO
Project description:Island populations repeatedly evolve extreme body sizes, but the genomic basis of this pattern remains largely unknown. To understand how organisms on islands evolve gigantism, we compared genome-wide patterns of gene expression in Gough Island mice, the largest wild house mice in the world, and mainland mice from the WSB/EiJ wild-derived inbred strain. We used RNA-seq to quantify differential gene expression in three key metabolic organs: gonadal adipose depot, hypothalamus, and liver. Between 4,000 and 8,800 genes were significantly differentially expressed across the evaluated organs, representing between 20% and 50% of detected transcripts, with 20% or more of differentially expressed transcripts in each organ exhibiting expression fold changes of at least 2×. A minimum of 73 candidate genes for extreme size evolution, including Irs1 and Lrp1, were identified by considering differential expression jointly with other data sets: 1) genomic positions of published quantitative trait loci for body weight and growth rate, 2) whole-genome sequencing of 16 wild-caught Gough Island mice that revealed fixed single-nucleotide differences between the strains, and 3) publicly available tissue-specific regulatory elements. Additionally, patterns of differential expression across three time points in the liver revealed that Arid5b potentially regulates hundreds of genes. Functional enrichment analyses pointed to cell cycling, mitochondrial function, signaling pathways, inflammatory response, and nutrient metabolism as potential causes of weight accumulation in Gough Island mice. Collectively, our results indicate that extensive gene regulatory evolution in metabolic organs accompanied the rapid evolution of gigantism during the short time house mice have inhabited Gough Island.
| S-EPMC7487164 | biostudies-literature
Project description:Large and giant congenital melanocytic nevi (CMN) are rare melanocytic lesions mostly caused by post-zygotic acquisition of NRAS alteration. However, large/giant CMN may exhibit phenotypic differences among distinct areas patients and in addition, patients differ in features such as presence of multiple CMN or Spilus-like lesions. Overall, 50 fresh-frozen biopsies corresponding to 37 phenotypically characterized areas of large/giant CMNs, 9 satellite lesions, 1 acquired nevus and 3 healthy skin biopsies were analyzed by a multigene panel and RNA sequencing (RNA-seq). Mutational screening showed mutations in 76.2% of large/giant CMN. NRAS mutation was found in 57.1% of cases, and mutations in other genes such as BRAF, KRAS, APC and MET were detected in 14.3% of patients. RNA-seq revealed the fusion transcript ZEB2-ALK and SOX5-RAF1 in large/giant CMN from two patients without point mutations. Both alterations were not detected in unaffected skin and were detected in different affected skin. These findings suggest that large/giant CMN may result from distinct molecular events in addition to NRAS mutations including point mutations and fusions transcripts.
2019-10-24 | GSE120597 | GEO
Project description:We characterized the mouse trophoblast giant cell epigenome and gene expression profiles. We then compared these data to our data on underrepresentation in the polyploid trophoblast giant cells. We profiled 5 histone modifications (+ chromatin input) using ChIP-Seq, and digital expression profiles (3' RNA-Seq) for trophoblast giant cells derived from mouse. Furthermore, we profiled digital expression profiles (3' RNA-Seq) for in vivo trophoblast giant cells samples from e9.5 wildtype mouse trophoblast giant cells. We found that underrepresented domains in trophoblast giant cells are enriched for repressive marks and anti-correlate with active marks and transcription.
2014-05-29 | E-GEOD-50561 | biostudies-arrayexpress
Project description:5-methylcytosine (5mC) is a widespread silencing mechanism that controls genomic parasites. However, in many eukaryotes 5mC has gained complex roles in gene regulation beyond parasite control. Animals are a paradigmatic case for 5mC evolution, as they show widespread variability across lineages, ranging from gene regulation and transposable element control to loss of this base modification. Here we show that the protist animal relative Amoebidium appalachense displays both transposon and gene body methylation, a pattern reminiscent of invertebrates and plants. Unexpectedly, large hypermethylated regions of the Amoebidium genome derive from viral insertions, including hundreds of endogenised giant viruses contributing 14% of the encoded genes. Using a combination of inhibitors and functional genomic assays, we demonstrate that 5mC silences these giant virus insertions. Moreover, alternative Amoebidium isolates show polymorphic giant virus insertions, highlighting a dynamic process of infection, endogenisation and purging. Therefore we propose that 5mC is critical for the controlled co-existence of newly acquired viral DNA into eukaryotic genomes, making Amoebidium a unique model to understand the hybrid origins of eukaryotic genomes.
2024-07-15 | GSE249241 | GEO
Project description:We characterized the mouse trophoblast giant cell epigenome and gene expression profiles. We then compared these data to our data on underrepresentation in the polyploid trophoblast giant cells.
2014-05-29 | GSE50561 | GEO
Project description:Giant cell granulomas of the jaws often occur sporadically as single central or peripheral lesions. They are characterized by KRAS, FGFR1, or TRPV4 somatic mutations, the latter occurring exclusively in the central form. Less commonly, multiple giant cell lesions can develop in the context of syndromes such as cherubism, which is an autosomal dominant bone disease. Morphologically, giant cell granulomas can closely resemble other giant cell-rich lesions such as non-ossifying fibroma and aneurysmal bone cyst, and to a minor extent giant cell tumour of bone and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and, recently, DNA methylation profile has been shown to be clinically useful for the diagnosis of other tumour types, including brain tumours as well as bone and soft tissue sarcomas. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic giant cell granulomas of the jaws and cherubism to test whether DNA methylation patterns can help to distinguish these entities. Additionally, we further compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. Our results showed that central and peripheral sporadic giant cell granulomas of the jaws and cherubism share a related DNA methylation pattern with that of peripheral sporadic giant cell granulomas and cherubism appearing slightly distinct, while central sporadic giant cell granulomas show overlap with both of the former. Non-ossifying fibroma, aneurysmal bone cyst, giant cell tumour of bone, and chondroblastoma, on the other hand, have distinct methylation patterns. Therefore, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions of the jaws. Conversely, it could discriminate sporadic giant cell granulomas from their giant cell-rich mimics.
2023-10-18 | GSE218252 | GEO
Project description:We characterized regions of underrepresentation that are specific to mouse polyploid trophoblast giant cells.
2014-05-29 | GSE50543 | GEO
Project description:We characterized regions of underrepresentation that are specific to mouse polyploid trophoblast giant cells. We performed array Comparative Genomics Hybridization (aCGH) to examine copy number variation (CNV) in mouse polyploid trophoblast giant cells (TGCs). We performed the following experiments in duplicates to examine CNV during various stages of in vivo and in vitro TGC development: e9.5 TGCs vs. embryonic controls, e11.5 TGCs vs. embryonic controls, e13.5 TGCs vs. embryonic controls, e16.5 TGCs vs. embryonic controls, as well as TGCs cultured 3, 5 and 7 days vs. 2N trophoblast stem cells. We also performed the following controls to show that underrepresentation is only found in polypoid trophoblast giant cells and not in either 2N placental cell types nor in other types of polyploid cells: 2N placenta disk vs. embryonic controls, 2N trophoblast stem cells vs. embryonic stem cells, and polyploid Megakaryocytes vs. embryonic controls. When possible, we performed arrays with the test and control samples of opposite sex (F-female, M-male), as an internal control for the array.
2014-05-29 | E-GEOD-50543 | biostudies-arrayexpress