PRIMATE_REG_EVOL · A comparative genomic study of the contribution of epigenetic mechanisms to regulatory evolution in primates
FP7 — People (Marie Curie Actions)
- Duration
- 2012-09-01 → 2015-08-31
- EU contribution
- €235,535
- Participants
- 1
- Scheme
- MC-IOF
Lines connect the coordinator with its partners.
Results in brief
A comparative genomic study of the contribution of epigenetic mechanisms to regulatory evolution in primates.
A long-standing hypothesis is that changes in gene regulation play an important role in adaptive evolution, notably in primates. Yet, in spite of the evidence accumulated in the past decade that regulatory changes contribute to many species-specific adaptations, we still know remarkably little about the mechanisms of regulatory evolution. In this study we focused on DNA methylation, an epigenetic mechanism whose contribution to the evolution of gene expression remains unclear. To interrogate the methylation status of the vast majority of cytosines in the genome, we performed whole-genome bisulfite conversion followed by high-throughput sequencing across 4 tissues (heart, kidney, liver and lung) in 3 primate species (human, chimpanzee and macaque). Because the 4 tissues are from the same individuals, we were able to monitor methylation differences between individuals, tissues and species. In parallel, we collected gene expression profiles using RNA-seq from the same tissue samples, allowing us to perform a high resolution scan for genes and pathways whose regulation evolved under natural selection. We analyzed and integrated these datasets to characterize better the genome features where methylation changes are associated with expression changes. Notably we developed a statistical model to quantify the proportion of variation in gene expression levels across tissues and species that can be explained by changes in methylation. At the conclusion of this work, these datasets allowed to determine the mechanisms that explain, at least in part, regulatory differences between the species.
Data: CORDIS, © European Union
Project objective
I propose to take first steps towards understanding the evolutionary processes that shape gene regulation in primates, and in particular, to study the mechanisms of regulatory change in humans and our close evolutionary relatives. By using RNA sequencing, I propose to study and compare gene expression phenotypes in multiple tissues and across species at unprecedented resolution, as well as to characterize exon usage and alternative splicing patterns. Subsequently, by using a combination of genomic approaches that will allow me to characterize histone modification marks and methylation profiles at genome-wide scale, I propose to move beyond simple inter-species comparisons of gene expression levels to the study of underlying regulatory mechanisms such as chromatin state and epigenetic markers. At the conclusion of this work I will have high-resolution gene expression data, methylation state, and histone modification profiles from a set of five tissues from multiple human, chimpanzee, and rhesus macaque individuals. These data will allow me to explore conserved inter-tissue regulatory differences, as well as to identify genes and pathways whose regulation evolved under natural selection in primates. In addition, my data will allow me to determine the mechanisms that explain, at least in part, regulatory differences between the species.
Original text from CORDIS.
Participants
- UNIVERSITE DE LAUSANNE · LAUSANNECoordinatorSwitzerland
Links
Data: CORDIS, © European Union