Using ancient DNA from three Neanderthal genomes, one Denisovan, and one ancient human (Ust'-Ishim), this project examines whether extinct members of the genus Homo had functionally distinct olfactory repertoires compared to contemporary humans. Novel variants were identified in 30 odorant receptor (OR) genes with known human receptor-odor relationships, then physically reconstructed using chimeric PCR and tested in luciferase cell assays -- the first experimental validation of OR function in ancient hominins at this scale. Extinct lineages showed more conserved OR sequences than living humans, but functional differences were in sensitivity rather than the range of odors detected: Neanderthal variants generally reduced OR sensitivity, while Denisovan variants increased sensitivity to sweet and sulfurous odors, suggesting possible ecological tuning to energy-dense foods following dispersal from Africa.
de March, C.A., Matsunami, H., Abe, M., Cobb, M., & Hoover, K.C. (2023). Genetic and functional odorant receptor variation in the Homo lineage. iScience, 26(1), 105908. DOI: 10.1016/j.isci.2022.105908
This repo contains two sets of files. All files prefixed revised- are revised scripts and figures from the original publication. Revisions consolidate original scripts (which contained functions that have deprecated or, in the case of Biostrings, moved to different librariers within Biostrings) and include environment management to future-proof the revised scripts. All other files are associated with the original publication. Occasionally, an original script may be updated with annotations for clarity; the commit history will note any such changes. In this case, the fastas are updated so that the names match the scripts.
- Original files:
HCscript-scrape_ancient_VCF_data_from_server.txt, DNA FASTA files (or*-dna.fas), amino acid FASTA files (or*-aa.fas,or*-aa-all.fa), original R scripts, functional assay data - Revised files: All revisions are prefixed,
revised-
The portfolio page includes a full project narrative, key findings, and figures.
Languages: R | Bash
Tools: VCFtools | BCFtools | HPC (University of Alaska Fairbanks)
Packages: dplyr | tidyr | ggplot2 | readxl | Biostrings | pwalign | ape | seqinr | phylogram | viridis | ggpubr
Demonstrates integration of computational genomics and experimental biology to test functional hypotheses about genetic variation -- a framework transferable to any domain requiring evidence-based inference from incomplete or ancient data sources.
- Code and scripts © Kara C. Hoover, licensed under the MIT License.
- Data, figures (except homology model and odorant activity table), and written content © Kara C. Hoover, licensed under CC BY-NC-ND 4.0.