Project description
Non-coding regions of DNA: their role in human adaptation and evolution
The evolution of protein-coding sequences of genomes is well understood, but the evolution of non-coding sequences controlling gene expression is not. Cis-regulatory elements including promoters, enhancers and silencers are important transcription controllers. It has been challenging to identify changes to them and link them to phenotypes. The ERC-funded RegEvoHum project will use cutting-edge approaches, human-ape hybrid cells and massively parallel reporter assays to identify cis-regulatory expression changes separating humans from apes and map their functions. Scientists will also develop a novel method to map the role of DNA methylation in shaping gene expression. Outcomes will begin to unravel the role of gene regulation in human evolution.
Objective
While the phenotypes that set us apart from our closest extinct and extant relatives have been largely demarcated, we are still far from understanding the genetics of human adaptation, and how these changes affect our current anatomy, physiology, and health. Most human adaptations have likely occurred in regulatory regions, particularly in cis-regulatory elements, such as promoters and enhancers. However, our ability to study cis-regulatory evolution is limited due to the complexity of identifying cis-regulatory changes and linking them to phenotypes.
We believe these limitations can now be tackled by merging several cutting-edge approaches, primarily hybrid cells and massively parallel reporter assays (MPRAs), augmented by developing sorely needed new ones. In Aim 1, we will generate human-ape hybrid cells and use them to identify the gamut of cis-regulatory expression changes separating humans from other apes. In Aim 2, we will perform MPRAs to map the function of each of the variants that distinguish modern humans, Neanderthals, Denisovans and apes. In Aim 3, we will develop methMPRA, a novel method to map the role of DNA methylation in shaping gene expression. In Aim 4, we will synergize these data to study human evolution at the sequence, methylation, expression and phenotypic level.
The proposed project will: (a) generate comprehensive resources, including the first catalogs of the sequence and methylation changes that shaped human gene regulation; (b) Develop a novel method to characterize en masse the cis-effects of methylation on expression; (c) Develop novel platforms (human-ape hybrid cells) to map human cis-regulation; and (d) Identify genetic changes underlying human traits. Together, this will pave the way to understanding the role of gene regulation in human evolution.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences zoology mammalogy primatology
- medical and health sciences basic medicine anatomy and morphology
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine physiology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2022-STG
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7610001 Rehovot
Israel
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