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Expression Patterns of Murine Antichymotrypsin-like Genes Reflect Evolutionary Divergence at the Serpina3 Locus

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Abstract

Members of the serpin (serine protease inhibitor) superfamily of genes are well represented in both human and murine genomes. In many cases it is possible to identify a definite ortholog on the basis of sequence similarity and by examining the surrounding genes at syntenic loci. We have recently examined the murine serpin locus at 12F1 and observed that the single human α1-antichymotrypsin gene is represented by 14 paralogs. It is also known that the single human α1-antitrypsin gene has five paralogs in the mouse. The forces driving this gene multiplication are unknown and there are no data describing the function of the various serpin gene products at the α1-antichymotrypsin multigene locus. Examination of the predicted amino acid sequences shows that the serpins are likely to be functional protease inhibitors but with differing target protease specificities. In order to begin to address the question of the problem presented by the murine α1-antichymotrypsins, we have used RT-PCR to examine the expression pattern of these serpin genes. Our data show that the divergent reactive center loop sequence, and predictably variable target protease specificity, is reflected in tissue-specific expression for many of the family members. These observations add weight to the hypothesis that the antichymotrypsin-like serpins have an evolutionary importance which has led to their expansion and diversification in multiple species.

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Acknowledgments

P.C. is a Wellcome Trust Senior Research Fellow. We are indebted to Dr. Robert Medcalf, Dr. Hong Yu, and Ms. Melinda Missen for helpful discussions and technical assistance.

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  1. Australian Centre for Blood Diseases, Alfred Medical Research Precinct, Monash University, Commercial Road, Prahran, 3181, Australia

    Anita J. Horvath, Sharon L. Forsyth & Paul B. Coughlin

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  1. Anita J. Horvath
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  2. Sharon L. Forsyth
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  3. Paul B. Coughlin
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Correspondence to Paul B. Coughlin.

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Horvath, A.J., Forsyth, S.L. & Coughlin, P.B. Expression Patterns of Murine Antichymotrypsin-like Genes Reflect Evolutionary Divergence at the Serpina3 Locus. J Mol Evol 59, 488–497 (2004). https://doi.org/10.1007/s00239-004-2640-9

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