Multiple Episodes of Convergence in Genes of the Dim Light Vision Pathway in Bats Yong-Yi Shen1,2, Burton K. Lim3, He-Qun Liu1,4, Jie Liu1,4, David M. Irwin5,6, Ya-Ping Zhang1,2* 1 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, China, 2 Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China, 3 Department of Natural History, Royal Ontario Museum, Toronto, Canada, 4 Graduate School of the Chinese Academy of Sciences, Beijing, China, 5 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, 6 Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada Abstract The molecular basis of the evolution of phenotypic characters is very complex and is poorly understood with few examples documenting the roles of multiple genes. Considering that a single gene cannot fully explain the convergence of phenotypic characters, we choose to study the convergent evolution of rod vision in two divergent bats from a network perspective. The Old World fruit bats (Pteropodidae) are non-echolocating and have binocular vision, whereas the sheath- tailed bats (Emballonuridae) are echolocating and have monocular vision; however, they both have relatively large eyes and rely more on rod vision to find food and navigate in the night. We found that the genes CRX, which plays an essential role in the differentiation of photoreceptor cells, SAG, which is involved in the desensitization of the photoactivated transduction cascade, and the photoreceptor gene RH, which is directly responsible for the perception of dim light, have undergone parallel sequence evolution in two divergent lineages of bats with larger eyes (Pteropodidae and Emballonuroidea). The multiple convergent events in the network of genes essential for rod vision is a rare phenomenon that illustrates the importance of investigating pathways and networks in the evolution of the molecular basis of phenotypic convergence. Citation: Shen Y-Y, Lim BK, Liu H-Q, Liu J, Irwin DM, et al. (2012) Multiple Episodes of Convergence in Genes of the Dim Light Vision Pathway in Bats. PLoS ONE 7(4): e34564. doi:10.1371/journal.pone.0034564 Editor: Eric James Warrant, Lund University, Sweden Received September 19, 2011; Accepted March 2, 2012; Published April 11, 2012 Copyright: 2012 Shen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by National Basic Research Program of China (973 Program, 2007CB411600), National Natural Science Foundation of China (30621092 and 31172080), Bureau of Science and Technology of Yunnan Province, and research grants from the ROM Governors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: zhangyp@mail.kiz.ac.cn Introduction Independent convergent evolution of phenotypic characters in response to similar selective pressures is not rare, however the molecular basis of these phenomena are poorly known [1,2]. In previous studies, a single gene is often used to explain the phenotypic convergence of echolocation in mammals and dim- light vision in bats [3,4,5]. The genetic makeup of these phenotypic characters is very complex and undoubtedly many other genes are involved in both echolocation and vision. For example, dim-light vision requires a series of genes, not only the visual pigment genes, but also genes that are involved in the desensitization of the photoactivated pigments, photoreceptor development, and visual signal transduction. Multiple genes are essential for functional rod vision. Bats are adapted to a nocturnal niche; however, their reliance on vision varies among species. Old World fruit bats (family Pteropodidae), for example, do not have laryngeal echolocation [6], and instead navigate largely by sight with larger eyes and binocular vision [7,8,9,10]. Other types of bats have laryngeal echolocation, and in general have smaller eyes with monocular vision [11,12,13]. An exception to this are the sheath-tailed bats (Emballonuridae) who have relatively large eyes and appear to have a greater reliance on visual sight compared to most bats [14,15]. The Emballonuridae with their relatively large superior colliculi resemble OW fruit bats in this respect [16], which may explain in part why both Emballonuridae and OW fruit bats both have well-developed visual systems [17]. The independent development of large eyes in Pteropodidae and Emballonuridae may reflect a functional convergence on the use of rod vision. Rod vision involves several processes, including light sensing, signal transduction, and interpretation in the brain cortex, among others, and thus many genes are involved [18,19]. A previous study indicated that convergent evolution in rhodopsin (RH1), a rod vision gene that encodes the pigment directly responsible for the perception of dim light [20], had occurred in Pteropodidae and Emballonuridae [5]. Rod vision requires many other genes, such as CRX, which encodes the cone-rod homeobox protein that is a photoreceptor-specific transcription factor essential for the differ- entiation of photoreceptor cells [21]. CRX regulates the expression of many rod vision-specific genes [22], and mutations in this gene cause autosomal dominant cone-rod dystrophy [23], autosomal dominant retinitis pigmentosa [24] and Leber’s congenital amaurosis [25,26]. Another gene involved in rod vision is SAG, which encodes S-arrestin protein, a major soluble photoreceptor protein that is involved in the desensitization of the photoactivated transduction cascade. Mutations in SAG are associated with night blindness [27,28]. While RH1 is essential for perception in dim light, CRX and SAG are also of critical importance for the function of photoreceptor cells and the animal’s ability to adapt to dim light. PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e34564