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One of the key objectives of comparative genomics is the characterization of the forces that shape genomes over the course of evolution. In the last decades, evidence has been accumulated that for vertebrate genomes also epigenetic modifications have to be considered in this context. Especially, the elevated mutation frequency of 5-methylcytosine (5mC) is assumed to facilitate the depletion of CpG dinucleotides in species that exhibit global DNA methylation. For instance, the underrepresentation of CpG dinucleotides in many mammalian genomes is attributed to this effect, which is only neutralized in so-called CpG islands (CGIs) that are preferentially unmethylated and thus partially protected from rapid CpG decay. For primate-specific CpG-rich transposable elements from the ALU family, it is unclear whether their elevated CpG frequency is caused by their small age or by the absence of DNA methylation. In consequence, these elements are often misclassified in CGI annotations. We present a method for the estimation of germ line methylation from pairwise ancestral-descendant alignments. The approach is validated in a simulation study and tested on DNA repeats from the AluSx family. We conclude that a predicted unmethylated state in the germ line is highly correlated with epigenetic activity of the respective genomic region. Thus, CpG-rich repeats can be facilitated as in silico probes for the epigenetic potential of their genomic neighborhood. [ABSTRACT FROM PUBLISHER]

Abstract: The exon–intron structure of eukaryotic genes allows for phenomena such as alternative splicing, nonsense-mediated decay, and regulation through untranslated regions. However, the evolution of the exon structure of genes is not well elucidated because of limited and phylogenetically sparse data sets. In this study, we use the phylogenetically diverse sequencing of the ENCODE regions to study gene structure evolution in mammalian genomes. This first phylogenetically diverse study of gene structure changes offers insights into the mode and tempo of mammalian gene structure evolution. The genes undergoing structure changes appear to be moderately to highly expressed in germline cells and show levels of selection similar to those of other ENCODE genes. Patterns of gene duplication of the affected genes are more complex than expected. The number of sampled genomes is sufficiently dense to infer that certain gene duplications happened after intron loss. Thus, although gene duplication is highly correlated with intron loss, we conclude that structural changes in genes are not necessarily due to a loss of constraint following gene duplication as previously suggested. [Copyright &y& Elsevier]