EAGER: Paleogenomic reconstruction and functional testing of archaic hominin olfactory receptors

University Of Alaska Fairbanks Campus, Fairbanks AK

Investigators

Abstract

The human sense of smell (olfaction) is central to many human activities and likely has a more complicated role in evolutionary pathways than previously suspected. Some examples of the important role olfaction plays in human behavior include detecting the fat content of food, directing food (and possibly mate) preference, and assessing health. Human olfaction is different from our closest living ape relatives, but it is not yet known if it is similar to or distinct from our extinct hominin relatives. The fundamental issue addressed by this project is whether or not genetic variation underlying odor detection receptors in the noses of modern humans, Neandertals, and Denisovans led to differences in how each species smelled the world. The investigators will use an innovative bioinformatics and laboratory approach to uncover rebuild key components of ancient noses. On a broad scale, the project promotes progress in the science of ancient genomes and evolutionary biology by assessing gene function in extinct populations. The data generated will contribute to human evolutionary genetics, biology, and anthropology. Application of these methods to other ancient genes has potential to transform our understanding of key evolutionary changes in humans, including genes implicated in human health and disease susceptibility. Finally, the project engages in public outreach to promote science education via a variety of national and international events, and includes funding to support training and professional development for under-represented individuals in STEM disciplines. This EAGER project will investigate whether the olfactory repertoires of ancient hominins are distinct from or overlap with modern humans. Specifically, the investigators will determine if novel variants in the paleogenomes of Altai Neandertals and Denisovans resulted in distinct olfactory repertoires, using variant calling in the paleogenomes of these two hominins, reconstruction of 30 paleo-olfactory receptors via overlap extension polymerase chain reaction, and experimental validation of functional responses to odorants via a high throughput Dual-Glo Luciferase Assay System. The study will be one of the first to validate function of paleogenes and the first to do so on a large number of genes related to olfaction, an understudied area of human evolution. Identifying variation in olfactory repertoires within a comparative evolutionary framework may advance our understanding of hominin dietary evolution and evolutionary ecology. The investigators introduce a method that could be used by other researchers to validate function in other paleogenes that might shed light on modern human health problems, using paleospecies as a model (alongside others) for gene function.