The Evolution of DNA methylation patterns in neurons of the frontal cortex of humans and non-human primates

• Applicant: Professor Dr. Thomas Haaf, since 7/2016
• Subject Area: Human Genetics
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280627290

In the evolutionary history of primates one of the most distinctive features among all traits attributed exclusively to the genus homo is brain size. Similar to enzephalization, communication abilities seem to evolve peaking in language which is uniquely assigned to humans and a key component of cognitive abilities. Language is suggested to be both a driving force as well as an outcome of brain acceleration. In order to understand the mechanisms behind brain evolution it is thus essential to understand the evolutionary roots as well as the biological and molecular basis of human specific communication abilities, in particular language, an issue best to be addressed through human-primate comparisons. Apart from the ongoing debates among linguists considering the faculty of language of human language, there seems to be a certain agreement that one key feature is the ability to assess mental states of other individuals. But particularly this essential competence is severely interfered with autism spectrum disorders (ASD). Inference from a genetic cause of a disease to the function of a gene is a common research approach, thus it is not surprising to note that prominent genes in ASD are as well considered as communication or language genes like for example CNTNAP2. Given the high similarity between the chimpanzee and human DNA sequences, comparisons of gene expression in these two species in the last decade indicated that gene regulation might have had a bigger impact on primate evolution than DNA sequence. Up to now only a minority of studies focussed on mechanisms underlying primate specific DNA methylation patterns. However, the most of these studies used bulk tissue for research on human and non-human primate brains instead of single cell types like neurons or glia cells. We suggest that during human brain evolution neuronal DNA methylation patterns developed differently between humans and primates.In order to adress this issue we want to apply laser captured microdissection (LCM) for the separation of neurons and other cell types from bulk brain tissue. Together with downstream technologies like Next Generation Sequencing (NGS)-based RNAseq and Reduced Representative Bisulfite Sequencing (RRBS), and Pyrosequencing, the outlined strategies will enable us to assess species specific methylation patterns as well as their impact on genomewide gene regulation and of selected candidate genes. This research project will provide insights into the molecular evolution of human communication/language as well as brain evolution and potentially can open up avenues for therapeutic interventions of ASD and associated language disorders.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Eberhard Schneider, until 6/2016