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Int J Biol Sci 2015; 11(9):1016-1025. doi:10.7150/ijbs.11751

Research Paper

Evolutionary History of Cathepsin L (L-like) Family Genes in Vertebrates

Jin Zhou1,2,3#, Yao-Yang Zhang4#, Qing-Yun Li4, Zhong-Hua Cai1,2,3 ✉

1. The Division of Ocean Science & Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, P. R. China
2. Shenzhen Public Platform of Screening & Application of Marine Microbial Resources, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, P. R. China
3. Shenzhen Key Laboratory for Coastal Ocean Dynamic and Environment, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, P. R. China
4. School of Life Science, Tsinghua University, Beijing, 100084, P. R. China
# These two authors contributed equally to this work.


Cathepsin L family, an important cysteine protease found in lysosomes, is categorized into cathepsins B, F, H, K, L, S, and W in vertebrates. This categorization is based on their sequence alignment and traditional functional classification, but the evolutionary relationship of family members is unclear. This study determined the evolutionary relationship of cathepsin L family genes in vertebrates through phylogenetic construction. Results showed that cathepsins F, H, S and K, and L and V were chronologically diverged. Tandem-repeat duplication was found to occur in the evolutionary history of cathepsin L family. Cathepsin L in zebrafish, cathepsins S and K in xenopus, and cathepsin L in mice and rats underwent evident tandem-repeat events. Positive selection was detected in cathepsin L-like members in mice and rats, and amino acid sites under positive selection pressure were calculated. Most of these sites appeared at the connection of secondary structures, suggesting that the sites may slightly change spatial structure. Severe positive selection was also observed in cathepsin V (L2) of primates, indicating that this enzyme had some special functions. Our work provided a brief evolutionary history of cathepsin L family and differentiated cathepsins S and K from cathepsin L based on vertebrate appearance. Positive selection was the specific cause of differentiation of cathepsin L family genes, confirming that gene function variation after expansion events was related to interactions with the environment and adaptability.

Keywords: cathespin L family gene, evolution, positive selection, functional divergence, environmental adaptability

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
How to cite this article:
Zhou J, Zhang YY, Li QY, Cai ZH. Evolutionary History of Cathepsin L (L-like) Family Genes in Vertebrates. Int J Biol Sci 2015; 11(9):1016-1025. doi:10.7150/ijbs.11751. Available from