PRIMATE_REG_EVOL

A comparative genomic study of the contribution of epigenetic mechanisms to regulatory evolution in primates

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 Obiettivo del progetto (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.

Descrizione progetto (Article)

The EU-funded PRIMATE_REG_EVOL project is focusing on the role of epigenetics in primate evolution. Involving chemical reactions that are not the result of changes in the DNA, the researchers are studying epigenetic changes in five tissues from humans, chimpanzees and rhesus macaque monkeys.

Regulatory mechanisms as a result of DNA methylation bring about differential regulatory systems. At the end of the project, the researchers expect to have a full set of gene expression data from the five tissues in the three primates. The result will be an opportunity to explore the conserved differences as well as the genes and pathways that have changed as a result of natural selection.

To monitor methylation status of four tissues in the three primates, the scientists used whole-genome bisulphite conversion. The process converts the base cytosine into uracil but leaves the methylated cytosine untouched. The data is then analysed to reveal species differences.

Using RNA sequencing, the project has also collected gene expression profiles to scan for genes and biochemical cascades that have changed through evolution. Integration of the data sets should show features of the genome whose methylation status gives rise to expression changes. Development of a model is underway to calculate the proportion of variation in gene expression across tissues and species that can be attributed to epigenetics, in particular methylation.

When data analysis is complete, understanding of evolution on the basis of gene regulation changes should be much enhanced. Overall, the research could serve as a platform to study evolution at the molecular level in general.