Hox cluster genomics in the horn shark, Heterodontusfrancisci

Hox cluster genomics in the horn shark, Heterodontusfrancisci

Departments of ^*Molecular, Cellular, and Developmental Biology, and ^¶Ecology and Evolutionary Biology, Yale University, New Haven, CT 06520; ^†Center for Human Genetics, Boston University School of Medicine, 700 Albany Street, W408, Boston, MA 02118; ^‡Merck and Company, Inc., Bioinformatics WP42–300, West Point, PA 19486; ^§Department of Molecular Biology, Keio University School of Medicine, 35 Shonano machi, Shinjuku, Tokyo 160, Japan; and ^‖Computer Science Department, Pennsylvania State University, 0326A Pond Laboratories, University Park, PA 16802

Contributed by Francis Ruddle

Abstract

Reconstructing the evolutionary history of Hox cluster origins will lead to insights into the developmental and evolutionary significance of Hox gene clusters in vertebrate phylogeny and to their role in the origins of various vertebrate body plans. We have isolated two Hox clusters from the horn shark, Heterodontus francisci. These have been sequenced and compared with one another and with other chordate Hox clusters. The results show that one of the horn shark clusters (HoxM) is orthologous to the mammalian HoxA cluster and shows a structural similarity to the amphioxus cluster, whereas the other shark cluster (HoxN) is orthologous to the mammalian HoxD cluster based on cluster organization and a comparison with noncoding and Hox gene-coding sequences. The persistence of an identifiable HoxA cluster over an 800-million-year divergence time demonstrates that the Hox gene clusters are highly integrated and structured genetic entities. The data presented herein identify many noncoding sequence motifs conserved over 800 million years that may function as genetic control motifs essential to the developmental process.

Footnotes

↵ ** To whom reprint requests should be addressed. E-mail: frank.ruddle{at}yale.edu.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF224262 and AF224263).
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.030539697.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.030539697
Abbreviations:

kb,

kilobase;

PAC,

P1 artificial chromosome;

RARE,

retinoic acid response element