COMMENTARY COMMENTARY Seeing is believing: Dynamic evolution of gene families Rayna M. Harris and Hans A. Hofmann1 Department of Integrative Biology, Center for Computational Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712

Educated by his deep appreciation of nature, duplication in actinopterygian (ray-finned) Darwin observed that “from so simple a be- fishes, but not in the sarcopterygian (lobe- ginning endless forms most beautiful” have finned) fishes, the lineage that includes arisen throughout the evolutionary history of land vertebrates (11). Even though most life on earth (1). The spectacular diversity of duplicated genes were secondarily lost, orchids (2) and beetles (3) has long fascinated many evolved new functions, in support naturalists and casual observers alike. More of the notion that gene and genome dupli- recently, the adaptive radiations of Hawaiian cations might provide a major mecha- Anolis drosophilids (4), Caribbean lizards (5), nism for generating phenotypic diversity and African cichlid fishes (6) have become in evolution (7). prime examples for understanding the mech- anisms that enable diversification. Gene Opsin Gene Family Expansion and Light duplication and deletion are generally Sensitivity considered important evolutionary mech- Opsin genes expressed in photoreceptor cells anisms that give rise to phenotypic diver- are fundamental to animal vision and are sity (7). Following gene duplication and amajorforceunderlyingtheevolutionary loss, adaptation and speciation appear to adaptation to variable photic environments proceed through a combination of both (12). The diversity of these genes is achieved structural and cis-regulatory changes in by gene duplication followed by changes in one or more paralogous genes (8). Recent amino acid sequence at key tuning sites. advances in sequencing technology have en- Opsins have been crucial to the successful abled researchers to make significant progress colonization of diverse habitats, especially in Fig. 1. Abbreviated history of violet-blue–sensitive (SWS2) in understanding the molecular evolution that teleost fishes, the most species-rich lineage genes in teleost fishes. The SWS2 gene was present in has facilitated diversification. In PNAS, Cor- of vertebrates. In a tour de force comparative a single copy before the neo-teleostei gene duplication, tesi et al. (9) examine the evolution of verte- which gave rise to SWS2A (light blue) and SWS2B paralogs genomics analysis, Cortesi et al. (9) describe (dark blue). In the percomorpha lineage, a subsequent brate opsin genes as a spectacular example of a newly discovered violet/blue short wave- duplication event gave rise to SWS2Aα and SWS2β paral- how gene duplication and deletion events length-sensitive 2 (SWS2) opsin, which arose ogs. Although these three paralogs have been retained that affect spectral sensitivity have driven ad- in many species, one or more paralogs have been lost in alongside the radiation of the highly diverse aptation to diverse light environments and percomorph fishes. The syntenic relationship is shown to percomorph fishes (which include cichlid visual displays. illustrate that these were tandem duplications occurring on fishes, wrasses, and other diverse and colorful the same chromosome, with example species listed below Gene families comprise several to many families). Specifically, the authors compared in parentheses. Modified from ref. 9. genes of similar nucleotide or amino acid almost 100 fish genomes to examine the sequences; they share similar cellular func- tions and commonly arise as a result of complex evolutionary history of SWS2, in- cluding numerous duplication, deletion, and Gene Family Evolution and Phenotypic gene or genome duplication events. The Diversification expansion or contraction of gene families pseudogenization events, and possibly even “ ” The evolution of opsin genes has received over evolutionary time in different line- the resurrection of functional genes from ample scrutiny, yet several other gene fami- ages can be random or the result of natural pseudogenes (Fig. 1). Several amino acid lies deserve mention because of their likely selection, although demonstrating the substitutions are described that likely facili- role in phenotypic diversification. One of latter can be difficult (10). Several mecha- tated the adaptive differentiation between nisms, such as tandem duplications, seg- SWS2 gene copies, probably by conferring the most spectacular examples comprises the mental duplications, or even whole-genome sensitivities to different wavelengths of light large and diverse family of olfactory receptor duplications can lead to the expansion of or by being differentially expressed as organ- gene families. Importantly, during the evolu- isms move through their ontogenetic and life Author contributions: R.M.H. and H.A.H. wrote the paper.

tion of chordates, the ancestral deutero- history stages. The study by Cortesi et al. (9) The authors declare no conflict of interest. stome genome (likely in a cephalochordate illustrates the complexity that results from See companion article 10.1073/pnas.1417803112. ancestor) experienced two rounds of whole- gene duplication and loss, and which in turn 1To whom correspondence should be addressed. Email: hans@ genome duplication followed by a genome enables the evolution of animal diversity. utexas.edu.

www.pnas.org/cgi/doi/10.1073/pnas.1423685112 PNAS Early Edition | 1of2 Downloaded by guest on October 1, 2021 genes, which vary widely in number across bind to receptors that belong to the nuclear It would be interesting to see future studies vertebrate genomes (13). For example, al- receptor family of transcription factors. These on the opsin gene family that incorporate though rodents have approximately 1,000 genes have coevolved with those that encode both an analysis of gene expression across olfactory receptor genes, humans have only the enzymes that synthesize steroids at key time or cell type with a bioinformatic anal- around 400 (a reduction likely caused by transitions in the evolution of vertebrates ysis of regulatory sequence evolution. massive loss and pseudogenization of olfac- and during gene family expansion (17), likely tory receptor genes in the human lineage). contributing to the diversification of verte- The Power of the Comparative Compared with mammals, the olfactory re- brates through their fundamental roles in Approach ceptor gene family is considerably more di- reproduction, development, homeostasis, and All these studies underscore the power of the verse in fishes (eight subfamilies are present), stress response. comparative approach for understanding yet the total number of olfactory receptor gene family evolution and, ultimately, the Integration of Functional and genes is much smaller, suggesting that the origins of animal diversity. Aristotle (in his mammalian olfactory receptor gene family Evolutionary Genomics book Peri Zoon Morion) already championed is much less complex compared with that in The study by Cortesi et al. (9) does not de- the promise of comparing different species the ancestor of vertebrates. Even though it scribe any analyses of regulatory sequence for achieving a deep understanding about evolution, nor do the authors investigate is often assumed that gene families evolve nature. If conducted within a phylogenetic tissue- or temporally specific gene-expression adaptively, signatures of selection are often framework, comparative analyses can provide patterns that may have arisen following reg- difficult to demonstrate. In this regard ol- inference similar to that obtainable with ex- ulatory changes. Coyne and Hoekstra (8) factory receptor genes also serve as a warning perimental approaches (19). Furthermore, argue that adaptation and speciation proceed against adaptive scenarios because the num- a deeper understanding of the detailed re- ber and types of olfactory receptor genes through a combination of both structural lationship between orthologous and paralo- apparently have evolved only in part in re- and cis-regulatory changes in one or more gousgenesiscrucialifwewanttofully sponse to environmental needs (13). paralogous genes. Regrettably, much of our capitalize on the wealth of data generated Voltage-gated sodium channels provide knowledge regarding the influence of struc- another compelling example, as they form tural and regulatory contribution to pheno- with comparative omics approaches. In an era the basis for electrical excitability in animals typic diversity comes from studies examining where biologists use fewer and fewer model (14). These sodium channels evolved from these two mechanisms in isolation rather systems, to the detriment of the entire bio- calcium channels and were present in the last than through concurrent examination in the medical research enterprise (20), the Cortesi common ancestor of choanoflagellates and same system. However, a recent study by et al. (9) paper provides a timely reminder for metazoa (animals), thus they already existed Harris et al. (18) combined structural, func- this notion, as it convincingly demonstrates when neurons first evolved. A motif that tional, and regulatory analyses to examine the a likely role for opsin gene evolution in the evolved early in chordate evolution allows evolution of the pro-opiomelanocortin gene ability of animals to conquer new niches and voltage-gated sodium channels to cluster family. By integrating temporal and spatial acquire new modes of communication. where action potentials are generated to expression measurements with sequence var- iation and regulatory interactions, these au- ACKNOWLEDGMENTS. Research in our laboratory is greatly enhance conduction velocity. After supported by National Science Foundation Grants IOS- the late Devonian extinction, when teleosts thors were able to shed new light on the 0843712 and IOS-1354942 (to H.A.H.) and DBI-0939454 and tetrapods each diversified in their re- mechanisms of phenotypic diversification. for the BEACON Center for the Study of Evolution in Action. spective habitats and the complexity of their brains increased concomitantly, the 1 Darwin C (1859) On the Origin of Species by Means of Natural 12 Carleton K (2009) Cichlid fish visual systems: Mechanisms of voltage-gated sodium channel gene family Selection. (J Murray, London). spectral tuning. 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In addition, these channels have 4 Kambysellis MP, Craddock EM (1997) Ecological and reproductive 109(Suppl 1):10619–10625. shifts in the diversification of the endemic Hawaiian Drosophila. 15 Zakon HH, Lu Y, Zwickl DJ, Hillis DM (2006) Sodium channel been selected to encode diverse communi- Molecular Evolution and Adaptive Radiation, eds Givnish TJ, genes and the evolution of diversity in communication signals of cation signals in weakly electric fish (15) Sytsma KJ (Cambridge Univ Press, Cambridge, UK), pp 475–509. electric fishes: Convergent molecular evolution. Proc Natl Acad Sci and to protect against lethal sodium chan- 5 Losos JB (2001) Evolution: A lizard’s tale. Sci Am 284(3):64–69. USA 103(10):3675–3680. 6 Brawand D, et al. (2014) The genomic substrate for adaptive 16 Billen B, Bosmans F, Tytgat J (2008) Animal peptides targeting nel toxins (e.g., in snakes, newts, pufferfish, radiation in African cichlid fish. Nature 513(7518):375–381. voltage-activated sodium channels. Curr Pharm Des 14(24):2492–2502. insects), providing unprecedented oppor- 7 Ohno S (1970) Evolution by Gene Duplication (Springer, 17 Baker ME, Nelson DR, Studer RA (2014) Origin of the response to tunities for drug design and therapeutic New York). adrenal and sex steroids: Roles of promiscuity and co-evolution of 8 Coyne JA, Hoekstra HE (2007) Evolution of protein expression: enzymes and steroid receptors. J Steroid Biochem Mol Biol, 10.1016/ applications (16). New genes for a new diet. Curr Biol 17(23):R1014–R1016. j.jsbmb.2014.10.020. Gene families involved in cell-to-cell sig- 9 Cortesi F, et al. (2014) Ancestral duplications and highly dynamic 18 Harris RM, Dijkstra PD, Hofmann HA (2014) Complex structural opsin gene evolution in percomorph fishes. Proc Natl Acad Sci USA, and regulatory evolution of the pro-opiomelanocortin gene family. naling appear to expand less in the course of 10.1073/pnas.1417803112. Gen Comp Endocrinol 195:107–115. evolution, possibly because the genes that 10 Hartl DL, Clark AG (2007) Principles of Population Genetics 19 Maynard-Smith J, Holliday R, eds (1979) Preface to Evolution of encode the receptors and ligands need to (Sinauer Associates, Sunderland, MA), 4th Ed. Adaptation by Natural Selection. Evolution of Adaptation by 11 Meyer A, Van de Peer Y (2005) From 2R to 3R: Evidence Natural Selection (The Royal Society, London). evolve in a coordinated manner. Examples for a fish-specific genome duplication (FSGD). BioEssays 27(9): 20 Bolker J (2012) Model organisms: There’s more to life than rats include steroid hormones, which classically 937–945. and flies. Nature 491(7422):31–33.

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