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Rapid Evolution of the Trophoblast Kunitz Domain Proteins (TKDPs)—A Multigene Family in Ruminant Ungulates

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Abstract

The trophoblast Kunitz domain proteins (TKDPs) are products of the outer cells (trophoblasts) of the placenta of cattle, sheep, and related species. Most are expressed abundantly for only a few days during the time at which the ruminant conceptus is first establishing intimate contacts with the uterine lining. The TKDPs are secretory proteins that possess a carboxyl-terminal peptidase inhibitory domain related to the Kunitz family of serine peptidase inhibitors. On the amino-terminal end are one or more highly unusual regions that are unique to the TKDP genes and have no apparent similarity to any other known sequences. The TKDPs are a rather divergent family that exhibits a good deal of variation among the members. To better understand the reason for such variation, the rates of synonymous (dS) and nonsynonymous (dN), as well as radical (p NR ) and conservative (p NC ), substitutions were assessed. Phylogenetic trees revealed that the Kunitz domains represented three related groups, whereas the amino-terminal domains formed four groupings. Pairwise comparisons between Kunitz and amino-terminal domain groups demonstrated that dN was consistently greater than dS. In addition, nonsynonymous substitutions in the Kunitz domains tended to be radical (changing charge or polarity), while those in the amino-terminal domains exhibited neither a preponderance of conservative nor radical substitution rates. In summary, the rapid evolution of the TKDPs, coupled with their restricted temporal expression during development, likely reflects the establishment of protein-protein interactions that have evolved to serve the unusual synepitheliochorial placenta of ruminant ungulates.

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Acknowledgments

This work was supported by the Animal Reproductive Biology Group of the University of Missouri—Columbia, Food for the Twenty-first Century Program, and NIH Grant HD21896.

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Author notes

  1. James A. MacLean II

    Present address: Department of Immunology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, 77054, USA

Authors and Affiliations

  1. Department of Veterinary Pathobiology, University of Missouri—Columbia, Columbia, Missouri, 65211, USA

    Anindita Chakrabarty & R. Michael Roberts

  2. Department of Biochemistry, University of Missouri–Columbia, Columbia, Missouri, 65211, USA

    James A. MacLean II & R. Michael Roberts

  3. Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, 29208, USA

    Austin L. Hughes

  4. Department of Animal Sciences, University of Missouri—Columbia, Columbia, Missouri, 65211, USA

    R. Michael Roberts & Jonathan A. Green

  5. University of Missouri—Columbia, 163 ASRC, 920 East Campus Drive, Missouri, 65211, USA

    Jonathan A. Green

Authors
  1. Anindita Chakrabarty
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  2. James A. MacLean II
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  3. Austin L. Hughes
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  4. R. Michael Roberts
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  5. Jonathan A. Green
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Correspondence to Jonathan A. Green.

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[Reviewing Editor: Dr. Martin Kreitman]

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Chakrabarty, A., MacLean, J.A., Hughes, A.L. et al. Rapid Evolution of the Trophoblast Kunitz Domain Proteins (TKDPs)—A Multigene Family in Ruminant Ungulates. J Mol Evol 63, 274–282 (2006). https://doi.org/10.1007/s00239-005-0264-3

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  • DOI: https://doi.org/10.1007/s00239-005-0264-3

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