1; Supplementary Fig. 10f), that are vital metabolic things in steroid and1; Supplementary Fig. 10f),

1; Supplementary Fig. 10f), that are vital metabolic things in steroid and
1; Supplementary Fig. 10f), which are essential metabolic elements in steroid and fatty acid metabolism, as well as genes encoding other hepatic enzymes involved in power balance processes. This enrichment is linked with considerable mTOR Modulator custom synthesis methylome divergence among species, in particular in promoter regions and gene bodies (Fig. 3d). For example, the gene sulfurtransferase tstd1-like, an enzyme involved in power balance and the mitochondrial metabolism, is expressed exclusively in the liver in the deep-water pelagic species D. limnothrissa, where it shows 80 reduced methylation levels ina gene-body DMR in comparison to each of the other species (Fig. 3e, h). A different example may be the promoter with the enzyme carbonyl reductase [NADPH] 1 (cbr1) which shows substantial hypomethylation (two.2kbp-long DMR) in the algae-eaters MZ and PG, connected with up to 60-fold improved gene expression in their livers compared to the predatory Rhamphochromis and Diplotaxodon (Fig. 3f, i). Interestingly, cbr1 is involved in the metabolism of various fatty acids within the liver and has been associated with fatty acid-mediated cellular signalling in response to environmental S1PR3 Agonist Compound perturbation51. As a final instance, we highlight the cytotoxic effector perforin 1-like (prf1-like), an essential player in liver-mediated power balance and immune functions52. Its promoter is hypermethylated (88 mCG/CG) exclusively in theNATURE COMMUNICATIONS | (2021)12:5870 | doi/10.1038/s41467-021-26166-2 | www.nature.com/naturecommunicationsNATURE COMMUNICATIONS | doi/10.1038/s41467-021-26166-ARTICLEFig. three Methylome divergence is connected with differential transcriptional activity in Lake Malawi cichlids. a Heatmap and unsupervised hierarchical clustering of gene expression values (Z-score) of all differentially expressed genes (DEGs) located among livers of four Lake Malawi cichlid species (Wald tests corrected for a number of testing employing false discovery price FDR 1 ). GO enrichment analysis for three DEG clusters are shown in Supplementary Fig. 9c. b Considerable overlap amongst DEG and differentially expressed regions (DMRs; p 0.05) linked to a gene (exact hypergeometric test, p = 4.71 10-5), highlighting putative functional DMRs (pfDMRs). c Bar plot displaying the percentage of pfDMRs localised in either promoters, intergenic regions (0.5-4kbp away from genes), or in gene bodies, together with the proportion of TE content material for every group. d Heatmap representing substantial GO terms for DEGs related with pfDMRs for every genomic feature. GO categories: BP, Biological Process; MF, Molecular Function. Only GO terms with Benjamini -Hochberg FDR-corrected p-values 0.05 are shown. Examples of pfDMRs significantly related with species-specific liver transcriptional adjustments for the genes thiosulfate:glutathione sulfurtransferase tstd1-like (LOC101468457; q = 6.82 10-16) (e), carbonyl reductase [NADPH]-1 cbr1-like (LOC101465189; MZ vs DL, q = 0.002; MZ vs RL, q = 1.18 10-7) (f) and perforin-1 prf1-like (LOC101465185; MZ vs DL, q = 3.68 10-19; MZ vs RL, q = 0.00034) (g). Liver and muscle methylome profiles in green and purple, respectively (averaged mCG/CG levels [ ] in 50 bp bins; n = 3 biological replicates for liver DL, PG, and MZ; n = 2 biological replicates for liver RL, AS, and AC, and muscle DL, RL, and PG). h-j Boxplots showing gene expression values (transcript per million) for the genes in (e-g). in livers (green) and muscle (pink). n = 3 biological replicates for liver DL, MZ, PG; n = two biological.