Odor molecules are detected by the olfactory receptors (hereafter OR) in the olfactory epithelium of the nasal cavity. Each receptor type is expressed within a subset of neurons, from which they directly connect to the olfactory bulb in the brain.Young, J. M., & Trask, B. J. (2002). "The sense of smell: genomics of vertebrate odorant receptors". Human Molecular Genetics, 11 (10), 1153-1160. Olfaction is essential for survival in most vertebrates; however, the degree to which an animal depends on smell is highly varied. Great variation exists in the number of OR genes among vertebrate species, as shown through bioinformatic analyses. This diversity exists by virtue of the wide-ranging environments that they inhabit. For instance, dolphins that are secondarily adapted to an aquatic niche possess a considerably smaller subset of genes than most mammals.Niimura, Y. (2012). "Olfactory receptor multigene family in vertebrates: from the viewpoint of evolutionary genomics". Current Genomics, 13(2), 103. OR gene repertoires have also evolved in relation to other senses, as higher primates with well-developed vision systems tend to have a smaller number of OR genes. As such, investigating the evolutionary changes of OR genes can provide useful information on how genomes respond to environmental changes. Differences in smell sensitivity are also dependent on the anatomy of the olfactory apparatus, such as the size of the olfactory bulb and epithelium.
Nonetheless, the general features of the olfactory system are highly conserved among vertebrates,Eisthen, H. L. (1997). "Evolution of vertebrate olfactory systems". Brain, Behavior and Evolution, 50 (4), 222-233. and, similarly to other sensory systems, olfaction has undergone fairly modest changes throughout the evolution of vertebrates. Phylogenetic analyses reveal that at least three distinct olfactory subsystems are broadly consistent in vertebrates, and a fourth accessory system (vomeronasal) solely arose in tetrapods.
Molecular evolution Mutations affecting OR genes on the chromosome are primarily responsible for the evolution of smell. OR genes are grouped in clusters along multiple chromosomes and are responsible for coding respective OR proteins. These proteins contain seven transmembrane domains that are responsible for detecting specific sets of odor molecules.Nei, M., Niimura, Y., & Nozawa, M. (2008). "The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity". Nature Reviews Genetics, 9 (12), 951-963. OR genes are located on error-prone regions of the chromosome, and consequently, the DNA of the OR gene is periodically duplicated during crossover. After this duplication event, one of the two genes may mutate and disable its function, rendering it as a pseudogene. Alternatively, the duplicated copy may mutate without dysfunctionality, and will continue making the same olfactory receptor but with altered structural changes. This protein adjustment can induce a subtle shift in the range of smells an animal can sense. The diversity of smelling genes present in humans today are attributed to multiple rounds of mutations that have occurred throughout vertebrate evolution.
In particular, repeated rounds of gene duplication, deletion, and pseudogene evolution contribute to the variety of OR gene number. Formally known as "birth-and-death evolution", these dynamics are measured by the number of gains and losses from genes in each branch of the phylogenetic tree in question. Statistical methods can be used to estimate the total number of gains and losses, which can be as large as several hundred per branch of the tree.Nozawa, M., & Nei, M. (2007). "Evolutionary dynamics of olfactory receptor genes in Drosophila species". Proceedings of the National Academy of Sciences of the United States of America, 104 (17), 7122-7127. Moreover, the number of gains and losses can be enormous even if two extant species possess the same gene number (for example, humans and macaques).
Both adaptation and random events can cause birth-and-death evolution. The probability of gene duplication is dictated by chance events and primarily occurs through unequal crossover; this excludes the rare event of whole genome duplication. Alternatively, the Fixation of duplicate genes can be influenced by natural selection or can occur randomly.Nozawa M, Kawahara Y, Nei M. (2007). "Genomic drift and copy number variation of sensory receptor genes in humans". Proceedings of the National Academy of Sciences of the United States of America. 104: 20421–20426. Within the mammalian phylogenetic tree, a large number of gene gains and losses are observed for almost all branches, suggesting that a significant fraction of gene number changes were caused by inactivation events and random gene duplication. This process is known as genomic drift, or "random genetic drift of gene frequencies" in population genetics. Pseudogenes are also subject to genomic drift, since they are rendered as non-functional and are believed to evolve in a neutral manner.Li, W. H., Gojobori, T., & Nei, M. (1981). "Pseudogenes as a paradigm of neutral evolution". Nature, 292 (5820), 237-239.
Lineage At least nine groups of vertebrate OR genes have been identified (α,β,γ,δ,ε,ζ,η, and θ), each of which derived from ancestral genes in the most common ancestor of tetrapods and fish. Specifically, vertebrate OR genes convey an evolutionary pattern of three separate lineages: fish, amphibians, and mammals.Niimura Y, Nei M. (2005). "Evolutionary dynamics of olfactory receptor genes in fishes and tetrapods". Proceedings of the National Academy of Sciences of the United States of America. 102 :6039–6044.
Early vertebrates and fish
Genetics Vertebrate olfaction was first derived in an aquatic ecosystem, where water was the primary medium for odorants. Lancelets, a class of marine chordates, are distant invertebrate relatives that share some of the same olfactory receptors (OR) with humans. They diverged from our own ancestors approximately 550 million years ago, before the development of camera eyes, semicircular canals and the tripartite brain. Although they lack an identifiable olfactory organ, lancelets possess 40 olfactory receptor genes that are studded along their flanks to detect odor molecules from their surrounding aquatic environment. Furthermore, many vertebrate-type olfactory receptor genes were found in their genome. The common ancestor of vertebrates and tunicates, the progenitor of the clade Olfactores, had developed the olfactory system more than the lancelets did.
Serving as living descendants that thrived almost half a billion years ago, the study of OR genes in lampreys also provides deep insight into the origins of vertebrate olfaction.Freitag, J., Krieger, J., Strotmann, J., & Breer, H. (1995). "Two classes of olfactory receptors in Xenopus laevis". Neuron, 15 (6), 1383-1392. Structural motifs that are characteristic hallmarks of vertebrate ORs were discerned when isolating OR genes expressed in lamprey olfactory organs. Phylogenetic analysis comparing the OR genes of fish and mammals revealed that lamprey ORs diverged from other vertebrates before the origin of Class I and II genes. It was also found that the lamprey OR gene repertoire was relatively small. Gene duplication and genetic drift expanded these small repertoires in gene number over evolutionary time, supporting the notion that the lamprey OR sequence represents an ancient OR family.Mezler, M. A. R. I. O., Konzelmann, S. I. D. O. N. I. E., Freitag, J. O. A. C. H. I. M., Rossler, P., & Breer, H. E. I. N. Z. (1999). "Expression of olfactory receptors during development in Xenopus laevis". The Journal of Experimental Biology, 202 (4), 365-376.
The vast diversity of olfactory organs is largely attributed to the long evolutionary lifespan of fish.Hara, T. J. (1975). "Olfaction in fish". Progress in Neurobiology, 5, 271-335. Representing an evolutionarily older class of vertebrates, fish carry several ancestral OR genes on their chromosome, yet they express wide variation in these genes among individuals and species.Shi, P., & Zhang, J. (2009). "Extraordinary diversity of chemosensory receptor gene repertoires among vertebrates". In Chemosensory Systems in Mammals, Fishes, and Insects (pp. 57-75). Springer Berlin Heidelberg. Fish have reduced olfactory systems in comparison to mammals since they only contain approximately 100 OR, whereas most mammals can possess 500 to 1000.
New phylogenomic analysis shows urochordates, rather than cephalochordates, as the sister group to vertebrates.Delsuc, F., Brinkmann, H., Chourrout, D., & Philippe, H. (2006). "Tunicates and not cephalochordates are the closest living relatives of vertebrate"s. Nature, 439 (7079), 965-968.Putnam, N. H., Butts, T., Ferrier, D. E., Furlong, R. F., Hellsten, U., Kawashima, T., ... & Rokhsar, D. S. (2008). "The amphioxus genome and the evolution of the chordate karyotype". Nature, 453 (7198), 1064-1071. All OR genes were lost in the lineage of urochordata because of the absence of any vertebrate-type OR-like genes. The loss of vertebrate type OR-genes therefore suggests that they may have been lost in the urochordates genomes (lost genes conserved between amphioxus and vertebrates).Holland, L. Z., Albalat, R., Azumi, K., Benito-Gutiérrez, È., Blow, M. J., Bronner-Fraser, M., ... & Vopalensky, P. (2008). "The amphioxus genome illuminates vertebrate origins and cephalochordate biology". Genome Research, 18 (7), 1100-1111.
Class I and Class II Phylogenetic analysis has delineated two main types of olfactory receptor genes that are traced back to early vertebrate OR history: class I genes, responsible for encoding proteins that detect water-soluble odorants, and Class II genes, associated with the detection of airborne molecules. Both types serve as homologous structures in fish and tetrapods.Mezler, M., Fleischer, J., & Breer, H. (2001). "Characteristic features and ligand specificity of the two olfactory receptor classes from Xenopus laevis". The Journal of Experimental Biology, 204 (17), 2987-2997.
In Xenopus laevis, an amphibia, both class receptors are present, unlike fish or mammals. Their class I receptors are expressed on the lateral diverticulum (LD), a region specialized to respond to water-soluble odorants, and class II receptors are abundantly present in the medial diverticulum (MD) which is specialized at detecting volatile odors.
Structure All fish perceive odors though nostril-like structures called nares. Most fish lack vomeronasal structures, yet they are still able to detect pheromones through vomeronasal-related genes. In lieu of the organ, fish possess sensory epithelium that contains three types of sensory cells, two of which are responsible for sex pheromones and social cures.Døving, K. B. (2002). "The alarm reaction in crucian carp is mediated by olfactory neurons with long dendrites". Chemical Senses, 27 (4), 395-398. Considering the slow diffusion of odor molecules through water, it is evolutionarily reasonable to possess only one type of cell dedicated to odorants and two cells dedicated to chemical communication.Hoover, K. C. (2010). "Smell with inspiration: the evolutionary significance of olfaction". American Journal of Physical Anthropology, 143 (S51), 63-74.
Selection