Collaborative research: Genotypic and phenotypic changes associated with encephalization.

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This research team is elucidating the genetic changes that orchestrated the expansion of the brain's neocortex during humankind's ancestry. This interdisciplinary team of scientists has compiled a list of genes that are important for the brain's anatomical development or its biochemical functioning. By utilizing the comparative genomic sequence data that are publicly available, the investigators are identifying in their list of brain-important genes those showing evidence of adaptive change in humankind's ancestry. The investigators intend to find out if such adaptive change is indeed associated with encephalization, the process that brought about brains with marked neocortical enlargements and increased cognitive capacities. To do so, the comparative gene sequence data will be enlarged to include a selection of other primates and other mammals. The species selected will allow testing of the hypothesis that those brain-important genes showing adaptive change in the lineage to humans will also show a higher frequency of adaptive change in non-human lineages where encephalization increased than in lineages where encephalization did not increase. For example, the investigators will compare the encephalized bottle-nosed dolphin (Tursiops truncatus) to the less encephalized odontocete sperm whale (Physeter macrocephalus) and mysticete blue whale (Balaenoptera musculus). In addition to the gene data, other types of molecular data on encephalization will also be gathered. To this end, the investigators will use immunohistochemical techniques to determine whether particular neuroanatomical structures show increasing levels of activity for genes involved in aerobic energy production in the series of macaques, chimpanzees and humans, a result that would correlate with the marked expansion of the neocortex in the human lineage. A database of neocortical phenotypic features will be constructed for a diverse range of primates and other mammals in order to search for cortical histological features that characterize the emergence of brains with increased cognitive capacities. Broader impacts include the establishment of a web site to disseminate these genotypic and phenotypic data that distinguish encephalized from non-encephalized lineages. Taken together, this work will further our goal of identifying the genetic underpinnings of humankind and determining which of the underpinnings are truly unique for humans. The interdisciplinary team of primatologists, biochemical geneticists, neuroscientists and anthropologists bridges diverse disciplines in order to elucidate the linked genotypic-phenotypic changes that shaped the human brain. By yielding a more objective view of the biological place of humans in nature, this research should have broad societal impact. Identifying the genetic changes that shaped the human brain could prove to be of great value in the search for new therapeutic agents in the field of mental health.