Lawi cichlid was discovered to have copies of DNA methyltransferases (DNMTs
Lawi cichlid was found to have copies of DNA methyltransferases (DNMTs) and ten-eleven translocation methylcytosine dioxygenases (TETs), the `readers’ and `erasers’ of DNA methylation respectively (Supplementary Fig. 4a-c). Like that of mammals along with other teleost fish, the genomes of Lake Malawi cichlids have high levels of DNA methylation genome-wide in the CG dinucleotide sequence context, regularly across all samples in each tissues analysed (Fig. 1d and Supplementary Fig. 2a-c). Gene bodies generallyshow higher methylation levels than the genome-wide TLR4 Agonist manufacturer typical, though the majority of promoter regions are unmethylated (Fig. 1d). CpG islands (CGIs; i.e., CpG-rich regions–abundant in Lake Malawi cichlid genomes; Supplementary Fig. 5a-i, Supplementary Notes and Methods) are just about entirely devoid of methylation in promoters, though `orphan’ CGIs, residing outdoors promoters, are mainly highly methylated (Fig. 1d and Supplementary Fig. 5f, g). While 70 of mammalian promoters contain CGIs41, only 15-20 of promoters in Lake Malawi cichlids harbour CGIs (Supplementary Fig. 5d), comparable to frog and zebrafish genomes41. Notably, orphan CGIs, which may have significant cis-regulatory functions42, compose up to 80 of all predicted CGIs in Lake Malawi cichlids (Supplementary Fig. 5e). In addition, repetitive regions, at the same time as transposable components, are specifically enriched for cytosine methylation, suggesting aNATURE COMMUNICATIONS | (2021)12:5870 | doi/10.1038/s41467-021-26166-2 | www.nature.com/naturecommunicationsARTICLENATURE COMMUNICATIONS | doi/10.1038/s41467-021-26166-methylation-mediated silencing of their transcription (Fig. 1d, Supplementary Fig. 6a-d), related to that observed in zebrafish as well as other animals8,18. Interestingly, specific transposon households, which include LINE I and Tc2-Mariner, part of the DNA transposon family–the most abundant TE household predicted in Lake Malawi cichlid genome (Supplementary Fig. 6a, b, Supplementary Notes, and ref. 38)–have lately expanded significantly in the Mbuna genome (Supplementary Fig. 6c and refs. 38,43). Even though Tc2-Mar DNA transposons show the highest median methylation levels, LINE I components have a number of the lowest, however most variable, methylation levels of all transposon families, which correlates with their evolutionary recent expansion within the genome (Fig. 1d, e and Supplementary Fig. 6d, e). Lastly, transcriptional activity in liver and muscle tissues of Lake Malawi cichlids was negatively correlated with methylation in promoter regions (Spearman’s NPY Y4 receptor Agonist custom synthesis correlation test, = -0.40, p 0.002), even though being weakly positively correlated with methylation in gene bodies ( = 0.1, p 0.002; Fig. 1e and Supplementary Fig. 7a-d and Supplementary Table 2). This is constant with previous studies highlighting high methylation levels in bodies of active genes in plants and animals, and high levels of methylation at promoters of weakly expressed genes in vertebrates8,24. We conclude that the methylomes of Lake Malawi cichlids share several regulatory attributes, and possibly linked functions, with those of other vertebrates, which renders Lake Malawi cichlids a promising model technique within this context. Methylome divergence in Lake Malawi cichlids. To assess the feasible role of DNA methylation in phenotypic diversification, we then sought to quantify and characterise the variations in liver and muscle methylomes across the genomes of Lake Malawi haplochromine cichlids. Despite general quite low sequence diverge.