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Evolution of Vertebrate Indoleamine 2,3-Dioxygenases

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Abstract

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes that catalyze the same reaction, the first step in tryptophan catabolism via the kynurenine pathway. TDO is widely distributed among life-forms, being found not only in eukaryotes but also in bacteria. In contrast, IDO has been found only in mammals and yeast to date. However, recent genome and EST projects have identified IDO homologues in non-mammals and found an IDO paralogue that is expressed in mice. In this study, we cloned the frog and fish IDO homologues and the mouse IDO paralogue, and characterized their enzymatic properties using recombinants. The IDOs of lower vertebrates and the mouse IDO paralogue had IDO activity but had 500–1000 times higher K m values and very low enzyme efficiency compared with mammalian IDOs. It appears that L-Trp is not a true substrate for these enzymes in vivo, although their actual function is unknown. On the phylogenetic tree, these low-activity IDOs, which we have named “proto-IDOs,” formed a cluster that was distinct from the mammalian IDO cluster. The IDO and proto-IDO genes are present tandemly on the chromosomes of mammals, including the marsupial opossum, whereas only the proto-IDO gene is observed in chicken and fish genomes. These results suggest that (mammalian) IDOs arose from proto-IDOs by gene duplication that occurred before the divergence of marsupial and eutherian (placental) mammals in mammalian evolutionary history.

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Acknowledgment

This work was partly supported by a Grant-in-Aid for Young Scientists B (to H.J.Y.) from the Japan Society for the Promotion of Science (KAKENHI 17770205).

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Authors and Affiliations

  1. Laboratory of Biochemistry, Department of Applied Science, Faculty of Science, National University Corporation Kochi University, Kochi, 780-8520, Japan

    Hajime Julie Yuasa, Miwa Takubo, Ayumi Takahashi, Tetsuo Hasegawa, Hiroshi Noma & Tomohiko Suzuki

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  1. Hajime Julie Yuasa
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  2. Miwa Takubo
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  3. Ayumi Takahashi
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  4. Tetsuo Hasegawa
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  5. Hiroshi Noma
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  6. Tomohiko Suzuki
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Correspondence to Hajime Julie Yuasa.

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Yuasa, H.J., Takubo, M., Takahashi, A. et al. Evolution of Vertebrate Indoleamine 2,3-Dioxygenases. J Mol Evol 65, 705–714 (2007). https://doi.org/10.1007/s00239-007-9049-1

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  • DOI: https://doi.org/10.1007/s00239-007-9049-1

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