Two Lamprey Hedgehog Genes Share Non-Coding Regulatory Sequences and Expression Patterns with Gnathostome Hedgehogs

Abstract

Hedgehog (Hh) genes play major roles in animal development and studies of their evolution, expression and function point to major differences among chordates. Here we focused on Hh genes in lampreys in order to characterize the evolution of Hh signalling at the emergence of vertebrates. Screening of a cosmid library of the river lamprey Lampetra fluviatilis and searching the preliminary genome assembly of the sea lamprey Petromyzon marinus indicate that lampreys have two Hh genes, named Hha and Hhb. Phylogenetic analyses suggest that Hha and Hhb are lamprey-specific paralogs closely related to Sonic/Indian Hh genes. Expression analysis indicates that Hha and Hhb are expressed in a Sonic Hh-like pattern. The two transcripts are expressed in largely overlapping but not identical domains in the lamprey embryonic brain, including a newly-described expression domain in the nasohypophyseal placode. Global alignments of genomic sequences and local alignment with known gnathostome regulatory motifs show that lamprey Hhs share conserved non-coding elements (CNE) with gnathostome Hhs albeit with sequences that have significantly diverged and dispersed. Functional assays using zebrafish embryos demonstrate gnathostome-like midline enhancer activity for CNEs contained in intron2. We conclude that lamprey Hh genes are gnathostome Shh-like in terms of expression and regulation. In addition, they show some lamprey-specific features, including duplication and structural (but not functional) changes in the intronic/regulatory sequences.

Involvement of Hedgehog and FGF signalling in the lamprey telencephalon: evolution of regionalization and dorsoventral patterning of the vertebrate forebrain

“…The genome of a closely related species, P. marinus, does not reveal any Hh homologues other than the orthologues of LjHhA, B and C. Two Hh homologues have been identified from another closely related species, Lampetra fluviatilis (Kano et al, 2010). Although the lack of sequence detail hinders confirmation of their orthology to any of the LjHh genes, LjHhA and LjHhB probably correspond to LfHha and LjHhb, respectively.…”

Genome Duplication in Early Vertebrates: Insights from Agnathan Cytogenetics

“…One possibility would be that 2R oc- curred within the gnathostome stem lineage after cyclostome divergence; however, molecular phylogenetic analyses of individual gene families have not clarified this issue [Kuraku et al, 2009]. Thus, it remains possible that both 1R and 2R occurred in the vertebrate stem lineage or that extra cyclostome genes are derived from independent duplications or a mixture of shared and independent duplications [Kano et al, 2010;Kuraku, 2011;Shimeld and Donoghue, 2012]. Recently, the chordate protokaryotype has been inferred by genome mapping analysis [Putnam et al, 2008], and a chromosomal complement of 2n = 34 (from 17 ancestral chordate linkage groups) was hypothesized before the 1R.…”

Why coelacanths are not ‘living fossils’

“…As a consequence, the idea that the coelacanth is a biological 'living fossil' is a long held but false belief which should not bias the interpretation of molecular data in extant Latimeria populations. The same reasoning could be generalised to other extant species (such as hagfish, lamprey, shark, lungfish and tatuara, to cite few examples of vertebrates) that for various reasons are often presented as 'ancient', 'primitive', or 'ancestral' even if a lot of recent data has shown that they have many derived traits [58][59][60][61][62][63][64]. We hope that this review will contribute to dispelling the myth of the coelacanth as a 'living fossil' and help biologists keep in mind that actual fossils are dead.…”