How an ancient genome duplication electrified modern fish.

A t various chapters in the story of life on earth, certain characters arise that seem to open the door for explosions of new forms and species. From the flowers of angiosperms to the mammary glands of mammals, these so-called evolutionary innovations represent new features that change the playing field of evolution and carry with them a cascade of biodiversity. Where these novelties come from remains a major mystery for biologists, because innovations are so different from traits in related species that it is difficult to imagine how evolution can build such unique features from accumulated changes in DNA sequence. A study published by Arnegard et al. (1) illustrates how a combination of ancient gene duplication and good oldfashioned natural selection works together to produce a communication organ that led to the origin of hundreds of species of electric fish in two hemispheres (Fig. 1). The myogenic electric organ has evolved repeatedly during the diversification of teleost fish (2). In some lineages, this organ exploits a sensory modality for communication entirely unique among vertebrates by producing electrical signals. Electric signals of these fish are analogous to acoustic songs of birds or insects, only sung in a different sensory realm. Two unrelated lineages of fish, the mormyroids of Africa and the gymnotiforms of South America, have evolved similar electric organs and use them to produce signals used in courtship and territoriality (3). Within each species, males and females produce recognizably different signals, and sexual selection seems to play a major role in the diversification of signal types (2). The electric signal represents a private communication channel that does not compete for bandwidth with other signals in the environment and can be detected only by closely related species (and a few specialized predators). Environmental factors that degrade acoustic and visual signals have no effect on electric signals, thus allowing electric fish to exploit habitats with relatively few competitors for space and resources. As a result of this evolutionary innovation, both the mormyroid and gymnotiform lineages have radiated into hundreds of species that represent a significant proportion of the species found in their local waters (2). But how does evolution build such a novel structure and function? The electric organ is developmentally derived from skeletal muscle and requires the synchronized firing of multiple electrocytes to generate the electric signal (4). Pulses in current generate the discharge, and voltage-gated sodium channels unique to teleost fish are known to underlie the discharges from the electric organ (5). Sodium channels, in general, are encoded by a family of genes expressed in different tissues, the structure of which is highly conserved both across taxa and across tissues within taxa. Minor changes in channel structure are known to compromise their function as part of the machinery propagating action potentials in nerves and muscle, resulting in devastating effects on fitness. The more specific question then is how can evolution take a gene so central to basic function as a sodium channel and coopt it for a new function in a novel organ (and do so two times)? The answer starts with gene duplication. Roughly, 225–300 mya, during the early evolution of fish, teleosts experienced a whole-genome duplication (6). Some of the duplicate genes produced in that ancestor have been retained and presumably acquired new functions, whereas others were long ago lost as nonfunctional units. The entire family of sodium channel genes (ScnA), which numbered four at the time of genome duplication, was duplicated and retained, generating the eight channel genes present in modern teleosts (7). At this duplication, the gene-encoding skeletal muscle channel became two forms, Scn4aa and Scn4ab. Both forms are still expressed in skeletal muscle in most fish and retain the basic sequence structure essential for propagation of transmembrane current (7). Using newly developed phylogenies of gymnotiforms and mormyroids, Arnegard et al. (1) are able to pinpoint the evolutionary transition, ∼100 Myr after the genome duplication, when one of these sodium channel forms, Scn4aa, was lost from skeletal muscle in two lineages. This event coincided with the origin of the electric organ and expression of Scn4aa in that tissue. Duplication of functional genes is thought to be an important route to evolutionary novelty, because one copy is free to accumulate mutations, whereas the other retains the original function (8). The puzzle of the electric fish story, however, is that the duplicate gene sat around for roughly 100 Myr without obvious function, expressed alongside another functional copy in the same tissue. The usual lifespan of a duplicate gene in animals is about 4 Myr (9). In this case, the Fig. 1. A whole-genome duplication occurred early in the evolution of teleost fish, producing duplicate copies of the sodium channel gene Scn4a that was expressed in skeletal muscle. The two sister genes, Scn4aa and Scn4ab, continued to be expressed in skeletal muscle and experienced purifying selection that maintained protein structure. Roughly 100 Myr later, the Scn4aa gene was co-opted into novel electric organs in two independent lineages of fish, the mormyroids in Africa and the gymnotiforms in South America. Coincident with this change of expression, Scn4aa experienced a sudden 10-fold increase in the strength of selection, whereas the sister gene, Scn4ab, did not. Selection fixed amino acid substitutions in identical regions (shown in red) of the NaV1.4a sodium channel in each fish lineage. Representative species and electric organ discharge are shown for momyroids (Campylomormyrus numenius; photo by J.P. Sullivan) and gymnotiforms (Sternopygus macrurus; photo by P.K. Stoddard).