Author(s): Hernando Herráez, I, Prado-Martínez J, Garg P, Fernandez-Callejo M, Heyn H, Hvilsom C, Navarro A, Esteller M, Sharp AJ, Marques-Bonet T
It has been hypothesized that differences between humans and their closet relatives may be explained by changes in gene regulation rather in primary genome sequence. Epigenetic alterations are involved in many biological processes and have been under-explored in comparative genomics. Specifically, DNA methylation is still poorly understood in the context of recent human evolution.
In this study, we performed a comparative analysis of CpG methylation patterns between 9 humans and 23 primates including all four species of great apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450 bead arrays. Using this approach, we were able to study the dynamics of DNA methylation and to identify regions showing species-specific methylation pattern among the great apes, including ~130 genes with a pattern unique to human. We also identified a significant positive relationship between the rate of coding variation and alterations of methylation at the promoter level, indicative of co-occurrence between evolution of protein sequence and gene regulation.
Multigene families are part of the pervasive Structural Variation (SV) present in eukaryotic genomes. In humans, regions with SV have been associated to disease and have been shown to participate in evolutionary innovation. Despite its widespread abundance and functional relevance, an accurate description of the underlying forces shaping the evolution of these regions is still lacking. In particular, the proper characterization of the interplay between mutation, crossover and gene conversion in multigene families is fundamental.
We have developed a forward-time simulation program that incorporates duplications and focuses on the effect of concerted evolution (the non-independent evolution of duplicated regions). By means of simulations, we have explored a wide range of parameters, gaining insight into the evolution of regions under concerted evolution such as the MHC. First, we observe that neutral concerted evolution can confound scans for selection by mimicking the effects of both weak purifying selection or weak positive selection. These effects can be more pronounced if duplicated regions are collapsed, as is frequent in low-quality genome assemblies. Additionally, we explore the effects of crossover hotspots in duplicated regions that present gene conversion activity. Our results show that multigene-family evolution is highly dependent on the spatial distribution of crossover and gene conversion events and their rates, even under neutrality.