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Abstract
Different human genes often exhibit different degrees of stability in their DNA methylation levels between tissues, samples or cell types. This may be related to the evolution of human genome. Thus, we compared the evolutionary conservation between two types of genes: genes with stable DNA methylation levels (SM genes) and genes with fluctuant DNA methylation levels (FM genes). For long-term evolutionary characteristics between species, we compared the percentage of the orthologous genes, evolutionary rate dn/ds and protein sequence identity. We found that the SM genes had greater percentages of the orthologous genes, lower dn/ds, and higher protein sequence identities in all the 21 species. These results indicated that the SM genes were more evolutionarily conserved than the FM genes. For short-term evolutionary characteristics among human populations, we compared the single nucleotide polymorphism (SNP) density, and the linkage disequilibrium (LD) degree in HapMap populations and 1000 genomes project populations. We observed that the SM genes had lower SNP densities, and higher degrees of LD in all the 11 HapMap populations and 13 1000 genomes project populations. These results mean that the SM genes had more stable chromosome genetic structures, and were more conserved than the FM genes.
Highlights
DNA methylation is an epigenetic mechanism [1, 2] that plays important roles in the regulation of gene expression [3, 4], development [5,6,7], X-chromosome inactivation [8] and genomic imprinting [9, 10].Some genomic regions can exhibit different methylation statuses among multiple samples [11]
The null hypothesis is that the SM genes and the FM genes had the same percentage of orthologous genes in each of the 21 species
The P-value was 9.54E-07 and the significance level α was 0.05. This indicated that the SM genes had a higher percentage of orthologous genes than FM genes across the 21 species
Summary
Some genomic regions can exhibit different methylation statuses among multiple samples (tissues, cell types or individuals) [11]. Other genomic regions may exhibit robust or stable methylation statuses between different tissues, samples or cell types. Two types of genes were considered: SM genes were defined as genes that have stable DNA methylation levels in all cell types of every tissue under normal or disease conditions. The DNA methylation statuses of SM genes were robust to environmental changes. FM genes were defined as genes that have fluctuant DNA methylation levels in different cell types, tissues, organisms or samples; i.e., FM genes were sensitive to environmental changes. We found a strong association between www.impactjournals.com/oncotarget the stability of DNA methylation levels and evolutionary conservation
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