Craniofacial divergence and ongoing adaptation via the hedgehog pathway

Abstract

Adaptive variation in craniofacial structure contributes to resource specialization and speciation, but the genetic loci that underlie craniofacial adaptation remain unknown. Here we show that alleles of the hedgehog pathway receptor Patched1 (Ptch1) gene are responsible for adaptive variation in the shape of the lower jaw both within and among genera of Lake Malawi cichlid fish. The evolutionarily derived allele of Ptch1 reduces the length of the retroarticular (RA) process of the lower jaw, a change predicted to increase speed of jaw rotation for improved suction-feeding. The alternate allele is associated with a longer RA and a more robustly mineralized jaw, typical of species that use a biting mode of feeding. Genera with the most divergent feeding morphologies are nearly fixed for different Ptch1 alleles, whereas species with intermediate morphologies still segregate variation at Ptch1. Thus, the same alleles that help to define macroevolutionary divergence among genera also contribute to microevolutionary fine-tuning of adaptive traits within some species. Variability of craniofacial morphology mediated by Ptch1 polymorphism has likely contributed to niche partitioning and ecological speciation of these fishes.T he astounding diversity of vertebrate craniofacial morphology reflects adaptation to a wide variety of resources and environments. Evolution of craniofacial structure has been key to niche specialization and speciation in vertebrates (1), most famously exemplified by the varied beak morphology of Darwin's finches (2). The radiation of finches demonstrates both speciesdefining craniofacial divergence (2) and rapid adaptation of craniofacial morphology within species over the course of a few years in response to changes in resource availability (3). Although shifts in the expression of key craniofacial genes have been correlated with differences in trophic morphology among species of birds and cichlid fishes (4-8), the specific genetic loci producing these differences remain uncharacterized. As a result, it is not clear whether interspecific divergence and intraspecific adaptation share the same molecular genetic basis.

Hedgehog signaling mediates adaptive variation in a dynamic functional system in the cichlid feeding apparatus

“…The results of this experiment were consistent with our previous work (Fig. 3): cyclopamine-treated LF larvae developed shorter RAs whereas the length of the mandible remained essentially unaffected (10). We also found that treated LF larvae exhibited IOP width/length ratios that were statistically indistinguishable from those of MZ (Fig.…”

“…The QTL peak was located squarely over the ptch1 locus (i.e., LOD peak of 6.25 at 25 cM, 95% CI, 18-42 cM). Although the CI associated with the QTL peak is large, our previous work has demonstrated, via association mapping among natural cichlid populations, that variation in jaw morphology is associated with a relatively narrow ∼10-kb genomic region located ∼15 kb upstream of the first ptch1 exon (10). As expected, the allelic effects of the IOP QTL on LG12 were consistent with the interspecific variation observed between parental species: inheritance of the ancestral (i.e., LF) ptch1 allele was associated with the development of a relatively wider and shorter IOP, whereas the derived (i.e., MZ) allele was associated with a relatively narrower and longer IOP.…”

“…At stage 17-18 [5.5-6 days postfertilization (dpf)], when bone development initiates in the head, we found considerable overlap among these genes. Specifically, ptch1 and gli1 are broadly expressed in the hyoid region of the skull, surrounding the IOP-mandibular ligament ( It was previously shown, via quantitative PCR, that ptch1 is differentially expressed in the craniofacial region between LF vs. MZ (10), with LF exhibiting relatively higher levels of expression. This can be visualized in the hyoid region of the pharyngeal skeleton via whole-mount in situ hybridization ( Fig.…”

“…In Lake Malawi cichlids, we have previously associated relatively simple shifts in trophic morphology with genetic variation in the receptor of the Hedgehog (Hh) signaling pathway, patched 1 (ptch1) (10). Specifically, we found two functionally distinct ptch1 alleles that produce quantitatively different amounts of transcript during early development (10) and affect the development of a specific bony process on the mandible, the retroarticular process (RA). The ancestral ptch1 allele, as inferred via the evolutionary history of the ptch1 locus among Lake Malawi cichlids (10), leads to a higher level of expression that results in more bone deposition and a longer RA.…”

“…In fact, most of the morphological and functional divergence between vertebrates can be found in the craniofacial region (1), which reflects adaptations to a wide variety of environments. It is therefore not surprising that myriad studies have investigated patterns of craniofacial divergence in various animals, including dogs (2, 3), bats (4), birds (5-7), and cichlids (8)(9)(10). Although recent efforts have started to associate variation in trophic morphology with differences in gene expression (5,6,(10)(11)(12)(13), the causative loci that underlie these differences remain largely unknown, especially in terms of complex and functionally relevant patterns of craniofacial divergence.…”