J Syst Evol ›› 2021, Vol. 59 ›› Issue (1): 169-182.DOI: 10.1111/jse.12587

• Research Articles • Previous Articles     Next Articles

Evolution and diversity of axon guidance Robo receptor family genes

Yi‐Qin Xu1, Xin Li1, Yang Zhong1, and Yu‐Fang Zheng2,3*   

  1. 1Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China
    2Institute of Reproduction and Development, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China
    3Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Fudan University, Shanghai 200433, China
  • Received:2018-11-05 Accepted:2020-04-07 Online:2020-04-10 Published:2021-01-01

Abstract: The diversity of axon guidance (AG) receptors reflects gains in complexity of the animal nervous system during evolution. Members of the Roundabout (Robo) family of receptors interact with Slit proteins and play important roles in many developmental processes, including AG and neural crest cell migration. There are four members of the Robo gene family. However, the evolutionary history of Robo family genes remain obscure. We analyzed the distribution of Robo family members in metazoan species ranging in complexity from hydras to humans. We undertook a phylogenetic analysis in metazoans, synteny analysis, and ancestral chromosome mapping in vertebrates, and detected selection pressure and functional divergence among four mammalian Robo paralogs. Based on our analysis, we proposed that the ancestral Robo gene could have undergone a tandem duplication in the vertebrate ancestor; then one round of whole genome duplication events occurred before the divergence of ancestral lamprey and gnathostome, generating four paralogs in early vertebrates. Robo4 paralog underwent segmental loss in the following evolutionary process. Our results showed that Robo3 paralog is under more powerful purifying selection pressure compared with other three paralogs, which could correlate with its unique expression pattern and function. Furthermore, we found four sites under positive selection pressure on the Ig1‐2 domains of Robo4 that might interfere with its binding to Slits ligand. Diverge analysis at the amino acid level showed that Robo4 paralog have relatively greater functional diversifications than other Robo paralogs. This coincides with the fact that Robo4 predominantly functions in vascular endothelial cells but not the nervous system.

Key words: axon guidance, evolution model, gene diversification, gene duplication, phyletic evolution, Robo gene family, selective pressure