Orphan Genes Find a Home: Interspecific Competition and Gene Network Evolution

Conservation of gene and protein sequence, and, therefore, conservation of the resulting molecular interactions that mediate biological processes, is foundational to our understanding of biology. This conservation allows discovery in one organism, such as worms or mice, to inform our understanding of the biology in another organism, such as humans. However, there is emerging recognition that many biological processes involve important non-conserved elements, and that de novo gene birth provides an important mechanism for functional evolution [1–3]. Understanding how these novel elements incorporate into gene regulatory networks and alter the network architecture is an important area for theoretical research [4–5], but few experimental examples have been described. Formation of the dauer larva by nematodes is an adaptation that is responsive to a variety of environmental cues and alterations, features that suggest the underlying gene regulatory network might benefit from enhanced robustness and evolvability [6]. The dauer larva is a relatively dormant, alternative developmental stage that nematodes enter under stressful conditions, such as low food or crowding (signaled by pheromone), that confers increased longevity and tolerance to stressors [7]. In many parasitic nematodes, this stage corresponds to the infective larval stage when the larvae transition to new hosts. There are important conserved components of the gene network that regulate dauer formation, one being the nuclear hormone receptor DAF-12, which is important in free-living as well as parasitic nematode species [8– 10]. However, it is also clear that this pathway is subject to considerable interand intraspecific differences [11–13]. Recent work on natural isolates of the nematode Pristionchus pacificus identified strain-specific phenotypic differences in dauer formation, and argued that genetically distinct populations exhibit greater sensitivity to pheromone from other populations (pheromone cross-preference [14]). The genetic alterations responsible for these phenotypic differences, however, had not yet been identified. A new paper in this issue of PLOS Genetics [15] provides an answer, and at the same time highlights how “orphan” genes can be incorporated into conserved regulatory networks. The authors started with two strains of P. pacificus that exhibited marked differences in response to pheromone signaling: the RS2333/California strain, with low dauer formation in response to pheromone, and the RS5134/Ohio strain, with a high response. They then generated 911 recombinant inbred lines (RIL) between the strains, and used Quantitative-Trait-Loci (QTL) mapping to identify a novel gene with no apparent orthologs outside of Pristionchus, dauerless (dau-1), that had undergone a duplication event in the RS2333/California strain. This suggested that dau-1 functions as a repressor of dauer formation in a dose-dependent manner. To test this hypothesis, the authors created transgenic lines with multiple copies of dau-1, and