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Maintenance of functional equivalence during paralogous Hox gene evolution

Nature volume 403, pages 661–665 (2000)Cite this article

Abstract

Biological diversity is driven mainly by gene duplication followed by mutation and selection. This divergence in either regulatory or protein-coding sequences can result in quite different biological functions for even closely related genes. This concept is exemplified by the mammalian Hox gene complex, a group of 39 genes which are located on 4 linkage groups, dispersed on 4 chromosomes1,2,3,4. The evolution of this complex began with amplification in cis of a primordial Hox gene to produce 13 members, followed by duplications in trans of much of the entire unit. As a consequence, Hox genes that occupy the same relative position along the 5′ to 3′ chromosomal coordinate (trans-paralogous genes) share more similarity in sequence and expression pattern than do adjacent Hox genes on the same chromosome. Studies in mice indicate that although individual family members may have unique biological roles, they also share overlapping functions with their paralogues5,6,7,8,9,10,11,12. Here we show that the proteins encoded by the paralogous genes, Hoxa3 and Hoxd3, can carry out identical biological functions, and that the different roles attributed to these genes are the result of quantitative modulations in gene expression.

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Figure 1: Representation of the wild-type (a) and one of the mutant Hox gene clusters (b).
Figure 2: Thymus and hyoid phenotypes of Hoxa3 null mutants and complementation by the Hoxa3D3 allele.
Figure 3: Atlas and axis phenotypes of Hoxd3 null mutants and complementation by the Hoxd3A3 allele.

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Acknowledgements

We thank all members of the Capecchi laboratory's tissue culture support group and animal care facility for their expertise. Assistance from L. Oswald, P. Reid and D. Lim for manuscript preparation, and R. Beglarian for histology is appreciated. J.M.G. was supported by the Dee Fellowship and a NIH Genetics Training Grant.

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  1. Howard Hughes Medical Institute, University of Utah School of Medicine , Salt Lake City, 84112, Utah, USA

    Joy M. Greer, John Puetz, Kirk R. Thomas & Mario R. Capecchi

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Correspondence to Mario R. Capecchi.

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Greer, J., Puetz, J., Thomas, K. et al. Maintenance of functional equivalence during paralogous Hox gene evolution . Nature 403, 661–665 (2000). https://doi.org/10.1038/35001077

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