Evidence for independent Hox gene duplications in the hagfish lineage: a PCR-based gene inventory of Eptatretus stoutii

Abstract

Hox genes code for transcription factors that play a major role in the development of all animal phyla. In invertebrates these genes usually occur as tightly linked cluster, with a few exceptions where the clusters have been dissolved. Only in vertebrates multiple clusters have been demonstrated which arose by duplication from a single ancestral cluster. This history of Hox cluster duplications, in particular during the early elaboration of the vertebrate body plan, is still poorly understood. In this paper we report the results of a PCR survey on genomic DNA of the pacific hagfish Eptatretus stoutii. Hagfishes are one of two clades of recent jawless fishes that are an offshoot of the early radiation of jawless vertebrates. Our data provides evidence for at least 33 distinct Hox genes in the hagfish genome, which is most compatible Manuscript 24 October 2003with the hypothesis of multiple Hox clusters. The largest number, seven, of distinct homeobox fragments could be assigned to paralog group 9, which could imply that the hagfish has more than four clusters. Quartet mapping reveals that within each paralog group the hagfish sequences are statistically more closely related to gnathostome Hox genes than with either amphioxus or lamprey genes. These results support two assumptions about the history of Hox genes: (1) The association of hagfish homeobox sequences with gnathostome sequences suggests that at least one Hox cluster duplication event happened in the stem of vertebrates, i.e., prior to the most recent common ancestor of jawed and jawless vertebrates. (2) The high number of paralog group 9 sequences in hagfish and the phylogenetic position of hagfish suggests that the hagfish lineage underwent additional independent Hox cluster/-gene duplication events.

Gene Duplications and Evolution of Vertebrate Voltage-Gated Sodium Channels

“…Based on our findings, it appears that one lamprey SCNA gene may have been lost, followed by an independent duplication of the remaining gene, thus giving the sister relationship of the 2 genes we found. This possibility is consistent with the facts that (1) SCNA genes are linked to the HOX clusters (Plummer and Meisler 1999) and (2) lampreys are believed to have undergone independent HOX cluster duplications after their divergence from other vertebrates (Fried et al 2003;Stadler et al 2004). However, due to the fact that SCNA genes are closely affiliated with the HOX clusters, our results do not provide independent support for the 2R hypothesis.…”

“…This tree is rooted with the two P. marinus sequences which group here as sister genes (100%). We believe these two sequences represent a unique gene or genome duplication in lampreys, which are also thought to have undergone independent Hox cluster duplications (see Fried et al 2003;Stadler et al 2004). However, re-rooting our tree with the lamprey genes as sister to one or the other of the two main groups, does not change the relationships between genes in the teleost and tetrapod lineages.…”

Timing and mechanism of ancient vertebrate genome duplications – the adventure of a hypothesis

“…The existence of one HoxA and one HoxD cluster (which implies that HoxB and HoxC should be present) in shark (Heterodontus francisci) places the 2R duplication before the emergence of cartilaginous fish [62]. For information on the number of Hox clusters in other species, see the following references: lamprey (Petromyzon marinus) [53,54], hagfish (Eptatretus stoutii) [61], zebrafish (Danio rerio) [50], pufferfish (S. nephalus) [51], medaka (Oryzia latipes) [52], Ciona (Ciona intestinalis) [79], coelocanth (Latimeria menadoensis) [80], amphioxus (Branchiostoma floridae) [3].…”

The duplication of the Hox gene clusters in teleost fishes*1

“…Higher ray-finned fishes, however, have 6 or 7 Hox clusters that arose by means of duplication from the ancestral gnathostome clusters [3]. The two agnathan lineages, lampreys and hagfish, also exhibit multiple Hox clusters which, however, apparently arose through duplication events independent of those leading to the gnathostome clusters [24,15,16,63]. Since Ohno's book on the role of gene duplication in evolution, the idea that gene and genome duplication played a major role in the origin of vertebrates has grown in support [46].…”