Funded Grants

Elucidating the molecular evolution of human cognition

Humans have uniquely adapted cognitive functions to carry out highly specialized tasks such as mathematics, language, musical compositions and art. What drives this human brain uniqueness? This has been a question that has fascinated us for some time. However, this strong curiosity and an abundance of research have yet to yield more than only a few insights into the biological underpinnings of human brain specializations.

The focus of my research is to identify the genes and molecular pathways that have uniquely evolved along the human lineage, and functionally understand the roles of these genes and pathways in human cognition. This approach provides an opportunity to understand human cognition at the genomic level. This analytical strategy, “cognitive genomics”, is ripe to deliver novel insights into human brain function. One of the long-lasting impacts of understanding evolved human cognition at a molecular level should be to facilitate breakthroughs that ameliorate disorders of cognition such as Alzheimer’s disease, schizophrenia, or autism. My research program is predicated on the hypothesis that vulnerability to cognitive disorders emerged as a consequence of the evolution of cognition itself. Therefore, we will understand these disorders by studying human brain evolution and vice versa.

While the human brain and the genetic networks that underlie the brain and its function are comprised of seemingly infinitely complex systems, a comparative species approach can deftly identify key factors that might drive evolved human cognition. This is because while humans have genetically similar building blocks to non-human primates in the form of genes, the identification of the combinatorial and regulatory network of these genes may provide insights into different organismal specializations and cognitive behaviors. My research has found that by taking a holistic and unbiased gene network approach that is akin to topological networks found in nature, complex gene expression patterns can be parsed into digestible units to identify functional underpinnings. For example, brain gene expression phylogeny is highly similar to known species phylogeny. However, my work has found evidence for accelerated evolution of gene coexpression or connectivity, and hence gene regulation, in the human brain. The functional consequences of this human modified brain network connectivity could impact a number of systems from cell type specification, synaptic development, intracellular signaling pathways, and/or neuronal activity, all of which would ultimately affect cognitive function.

With support from the James S. McDonnell Foundation, I propose to use comparative genomics and coexpression networks to address the question: what makes human cognition unique at the molecular level? I further propose to determine the functional significance of this evolved genomic connectivity. Human gene expression patterns will be identified by comparing humans to other closely related species. These human brain expression patterns will be related to functional measurements of human brain activity (e.g. fMRI and EEG). Salient genes identified will be functionally characterized to further delineate the molecular mechanisms of unique human cognition. This proposed research program should advance our understanding of how to connect human cognition to evolved molecular mechanisms at the level of genomic networks.