1. Collaborators  Donald R. Frohlich University of St. Thomas University of St. Thomas  Jae-Ho Kim Rogers State University Rogers State University  Gary B. Ogden St. Mary’s University St. Mary’s University  Brenda S. Whaley Houston Baptist University Houston Baptist University

2. Why do Humans Smell so Bad ly ??

3. Introduction  Olfactory receptor (OR) genes provide the basis for the sense of smell and, with more than 1,000 genes, comprise the largest gene superfamily in mammalian genomes.  All OR genes are 7 pass transmembrane receptors and have an approximately 1 kb coding region that is uninterrupted by introns.

4. General Observation  Many mammals, dogs especially, are known to have an acute sense of smell.  By comparison humans are practically anosmic.

5. Major Question  Is there a molecular/cell biological explanation for why humans smell so badly?

6. Possible Student Answers  H. sapiens may have fewer OR genes, as compared with dogs and/or other mammals.  Humans may have fewer functional OR genes (i.e., a higher proportion of pseudogenes).  Other?

7. What Does the Literature Say about this Topic?  Approximately 60% of human OR genes carry one or more coding region disruptions and are therefore considered pseudogenes.  In nonhuman apes, the fraction of OR pseudogenes is only approximately 30%.  Both humans and other apes have a significantly higher fraction of OR pseudogenes than do the mouse (20%) or the dog (12%).  A decrease in the size of the intact olfactory repertoire occurred independently in two evolutionary lineages: in the ancestor of Old World Monkeys and apes, and in the New World howler monkey.  Some speculate that the high fraction of OR pseudogenes in some primates may reflect a decreased reliance on the sense of smell in species for whom auditory cues and full trichromatic vision may be more important.

8. From: Gilad, et. al., PLOS Biology (2) 2004.

9. Phylogenetic Tree of Primates. From: Gilad, et. al., PLOS Biology (2) 2004. Arrow marks lineage acquiring trichromatic color vision, red marks lineages with high Frequency of OR pseudogenes.

10. From: Niimura and Nei, Gene (346) 2005. Evolutionary changes in the number of functional OR genes in mice and humans. MRCA = most recent common ancestor.

11. Our Approach  Ask students to provide molecular/cell biological explanations for the observation that humans have a poor sense of smell, as compared with dogs and many other mammals.  After discussion, ask the students to obtain data to support/refute the hypothesis that “humans have an increased frequency of OR pseudogenes, as compared to dogs.”  Ask each student to choose, at random, 5-10 functional canine OR genes from a database (source provided) and determine if the human ortholog for each dog gene is an actual (functional) OR gene or a pseudogene (i.e., a sequence with one or more coding region disruptions).  The frequency of human OR pseudogenes will be determined for the data compiled from the entire class, and be compared with the known frequency of OR pseudogenes in dogs (i.e., 12%).

12. Link: www.bip.weizmann.ac.il/HORDE Dog/Human/Chimp/Mouse OR Database

13. Linked to: www.bip.weizmann.ac.il/HORDE