Lawi cichlid was found to have copies of DNA methyltransferases (DNMTs
Lawi cichlid was identified to have copies of DNA methyltransferases (DNMTs) and ten-eleven translocation methylcytosine dioxygenases (TETs), the `MT1 Agonist Gene ID readers’ and `erasers’ of DNA methylation respectively (NF-κB Inhibitor custom synthesis Supplementary Fig. 4a-c). Like that of mammals and other teleost fish, the genomes of Lake Malawi cichlids have higher levels of DNA methylation genome-wide inside the CG dinucleotide sequence context, regularly across all samples in both tissues analysed (Fig. 1d and Supplementary Fig. 2a-c). Gene bodies generallyshow larger methylation levels than the genome-wide typical, while 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 Strategies) are pretty much totally devoid of methylation in promoters, while `orphan’ CGIs, residing outdoors promoters, are mostly hugely methylated (Fig. 1d and Supplementary Fig. 5f, g). Whilst 70 of mammalian promoters include 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 important cis-regulatory functions42, compose as much as 80 of all predicted CGIs in Lake Malawi cichlids (Supplementary Fig. 5e). Moreover, repetitive regions, as well as transposable components, are particularly 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), comparable to that observed in zebrafish and other animals8,18. Interestingly, certain transposon households, for instance LINE I and Tc2-Mariner, part of the DNA transposon family–the most abundant TE family members predicted in Lake Malawi cichlid genome (Supplementary Fig. 6a, b, Supplementary Notes, and ref. 38)–have not too long ago expanded considerably within the Mbuna genome (Supplementary Fig. 6c and refs. 38,43). Whilst Tc2-Mar DNA transposons show the highest median methylation levels, LINE I components have some of the lowest, yet most variable, methylation levels of all transposon families, which correlates with their evolutionary current expansion inside the genome (Fig. 1d, e and Supplementary Fig. 6d, e). Finally, transcriptional activity in liver and muscle tissues of Lake Malawi cichlids was negatively correlated with methylation in promoter regions (Spearman’s correlation test, = -0.40, p 0.002), whilst becoming 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 can be constant with earlier research 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 a lot of regulatory characteristics, and possibly connected functions, with those of other vertebrates, which renders Lake Malawi cichlids a promising model technique in this context. Methylome divergence in Lake Malawi cichlids. To assess the doable role of DNA methylation in phenotypic diversification, we then sought to quantify and characterise the differences in liver and muscle methylomes across the genomes of Lake Malawi haplochromine cichlids. In spite of all round incredibly low sequence diverge.