Once a rock star makes it big, they treat the world to a tour. However, DNA methylation, being both an epigenetic rock star and an unbearable diva, has been more than fashionably late to the party! But fear not! DNA methylation has made a comeback with a hit record of scientific insight into human diversity.
In this case, the lab of Hunter Fraser at Stanford University made use of the Human Genome Diversity Cell Line Panel, where they obtained lymphoblastoid cell lines from 34 individuals belonging to five diverse populations (6 Siberian Yakut, 7 Cambodian, 7 Pakistani Pathan, 7 Algerian Mozabite, and 7 Mexican Mayan).
To decipher epigenetic diversity, the team examined SNP genotypes, CpG methylation with the 450K array, and mRNA levels via RNA-Seq, where:
- Principal component analysis (PCA) and hierarchical clustering of the SNP genotypes robustly differentiates the individuals into their populations
- CpGs with population specific methylation differences tend to locate to gene bodies, downstream of the first exon, rather than at promoters
- The promoter associated sites typically occur in the CpG shores and shelves, rather the CpG islands that they flank
- The team confirmed the top three CpG sites using pyrosequencing
- While a strong relationship exists between population-specific DNA methylation, gene expression, and genotypes, the link between DNA methylation and SNPs is the stronger than that of gene expression and SNPs
- The CpGs with the highest degree of population specificity more strongly associated with a nearby SNP (26% of variance) than the actual population the individual is from (6.2 of variance), a pattern that is not as pronounced for gene expression
The team also notes that human DNA methylation appears to exhibit more evolutionary stability than plants, specifically Arabidopsis thaliana. Overall, these findings provide some much-needed insight into the DNA methylation profiles of diverse human populations, where they highlight the complex roles of genetic background and the environment in shaping human methylomes.
Go take the world tour over at Nature Ecology & Evolution, August 2017