Hox cluster genomics in the horn shark, Heterodontus francisci - PubMed (original) (raw)

Hox cluster genomics in the horn shark, Heterodontus francisci

C B Kim et al. Proc Natl Acad Sci U S A. 2000.

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.

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Figures

Figure 1

Figure 1

Comparisons of Hox gene spacing and gene dropouts between the amphioxus Hox cluster (Amp), human HoxA (HoxA), Fugu HoxA (FuguA; ref. 21), Heterodontus HoxM (HoxM), mouse HoxB (HoxB), mouse HoxC (HoxC), Heterodontus HoxN (HoxN), and mouse HoxD (HoxD) clusters. Spacing between gene coding regions is based on contig and sequence analysis. GenBank accession numbers for the human HoxA cluster are AC004079 and AC004080. Dotted lines indicate extensions not yet sequenced. The scale below Amp is for Amp only, and the scale below HoxN is for the other clusters.

Figure 2

Figure 2

Phylogenetic relationships between Hox9 genes and Evx. Numbers above the lines are bootstrap values obtained in 1,000 replicates for maximum parsimony. (A) Phylogenetic analysis of amino acid sequences of exons 1 and 2 of Hox9 genes of human, mouse, zebrafish, and horn shark. (B) Phylogenetic analysis of nucleotide sequences of Evx-1 and Evx-2 of human, mouse, and zebrafish and EvxN of horn shark.

Figure 3

Figure 3

Comparisons of nucleotide sequence between human HoxA, Heterodontus HoxM, and HoxN Hox clusters. Sequence comparisons are based on the human HoxA cluster as a reference. Kilobase (k) markings relate to the human HoxA cluster. Actual spacings between genes and gene dropouts are shown in Fig. 1. Color codes and symbols are as follows. Blue signifies coding regions. Yellow indicates weakly conserved noncoding regions. Orange indicates strongly conserved noncoding regions. Red indicates noncoding sequences conserved in both Heterodontus HoxM and HoxN clusters at the same position. The long horizontal arrows indicate direction of transcription. Tall black boxes indicate protein coding regions. Tall open boxes show, where possible, untranslated regions of a gene as determined from mRNA sequences in GenBank (namely, Evx-1, HoxA10, HoxA9, and HoxA4). Medium size open boxes (e.g., at position 13.9k) denote simple repeats and low-complexity regions. Short open boxes (e.g., 4k) demarcate CpG islands, with open boxes indicating a CpG/GpC ratio between 0.6 and 0.75 and gray indicating a ratio above 0.75. Interspersed repeat elements are shown as triangles and pointed boxes, where black triangles signify MIR elements, light gray triangles represent SINES other than MIR, light gray pointed boxes designate LINE1, and dark gray represent all other repetitive elements. Asterisks (*) in the middle of exons of Hox6 and Hox7 genes of HoxN indicate gene dropouts of those Hox genes in HoxN cluster.

Figure 4

Figure 4

Alignments of HB-1, retinoic acid response elements (RAREs), and the Hox8/Hox7–Hox6 four cluster sequences (H8/7–6 FCS). (A) Alignment of HB-1 elements located in the intron of the HoxA4 gene. The yellow box indicates the HB-1 element, and the gray box represents the other conserved motifs. The second gray box located upstream of the HB-1 element shows similarity to a consensus site found within the _Pax_-6 paired domain. (B) RAREs previously reported (29, 30) were detected and mapped to 122 kb. (C) Alignment of the H8/7–6 FCS. These sequences exist in all four clusters downstream of HoxA7, HoxB7, HoxD8, and HoxC8. Gray boxes indicate conserved regions in FCS. Mo., mouse; Hu., human.

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