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Molecular Evolution of Three Avian Neurotrophin Genes: Implications for Proregion Functional Constraints

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Abstract

Neurotrophin proteins are essential for the survival, differentiation, and maintenance of neurons in the peripheral and central nervous systems. Recent studies have shown that the unprocessed proforms of the neurotrophins are preferential high-affinity ligands for p75NTR and potent inducers of p75NTR-mediated cell death. Here, we explore differences in the selective constraints acting on the proregions of the three avian neurotrophin genes—NT-3, BDNF, and NGF—in an explicit phylogenetic context. We found a 50-fold difference in levels of constraint as estimated by d N/d S ratios, with the NGF proregion showing the lowest degree of constraint and BDNF the highest. These patterns suggest that the high conservation exhibited by the BDNF proregion results from intense functional constraints that are relaxed in NGF and somewhat relaxed in NT-3. The proregion of BDNF is likely to have a function that differentiates it from the corresponding regions of the NGF and NT-3 genes, suggesting that BDNF is the avian neurotrophin most likely to be used both in its precursor and mature forms in vivo.

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Acknowledgements

We thank Tom Smith for samples and support at the Center for Tropical Research, Robert Ricklefs and Lisa Tell for additional samples, and Sonya Clegg, Finn Hallböök, and Enrique Lessa, for comments on an early version of the manuscript. We thank Carlos Ibañez for insightful suggestions and Rasmus Nielsen for advice on data analysis. R.N.M.S. was supported by a Research Infrastructure in Minority Institutions award from the National Center for Research Resources with funding from the Office of Research on Minority Health, National Institutes of Health Grant 5 P20 RR11805. R.N.M.S. was also supported by an NIGMS MORE Institutional Research and Academic Career Development Award to UC Davis and San Francisco State University, (http://prof.ucdavis.edu/ ; Grant K12GM00679). This work was also funded by Grants NSF-DEB9726425 and NSF-IRCEB9977072.

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Authors and Affiliations

  1. Center for Tropical Research, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA

    Ravinder N. M. Sehgal

  2. Evolutionary Biology Program, Cornell Laboratory of Ornithology, 159 Sapsucker Woods Road, Ithaca, NY 14850, USA

    Irby J. Lovette

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  1. Ravinder N. M. Sehgal
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Correspondence to Ravinder N. M. Sehgal.

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Sehgal, R.N., Lovette, I.J. Molecular Evolution of Three Avian Neurotrophin Genes: Implications for Proregion Functional Constraints . J Mol Evol 57, 335–342 (2003). https://doi.org/10.1007/s00239-003-2484-8

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  • DOI: https://doi.org/10.1007/s00239-003-2484-8

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