Conserved Molecular Players Involved in Human Nose Morphogenesis Underlie Evolution of the Exaggerated Snout Phenotype in Cichlids

Abstract

Instances of repeated evolution of novel phenotypes can shed light on the conserved molecular mechanisms underlying morphological diversity. A rare example of an exaggerated soft tissue phenotype is the formation of a snout flap in fishes. This tissue flap develops from the upper lip and has evolved in one cichlid genus from Lake Malawi and one genus from Lake Tanganyika. To investigate the molecular basis of snout flap convergence, we used mRNA sequencing to compare two species with snout flap to their close relatives without snout flaps from each lake. Our analysis identified 201 genes that were repeatedly differentially expressed between species with and without snout flap in both lakes, suggesting shared pathways, even though the flaps serve different functions. Shared expressed genes are involved in proline and hydroxyproline metabolism, which have been linked to human skin and facial deformities. Additionally, we found enrichment for transcription factor binding sites at upstream regulatory sequences of differentially expressed genes. Among the enriched transcription factors were members of the FOX transcription factor family, especially foxf1 and foxa2, which showed an increased expression in the flapped snout. Both of these factors are linked to nose morphogenesis in mammals. We also found ap4 (tfap4), a transcription factor showing reduced expression in the flapped snout with an unknown role in craniofacial soft tissue development. As genes involved in cichlid snout flap development are associated with human mid-line facial dysmorphologies, our findings could hint at the conservation of genes involved in mid-line patterning across distant evolutionary lineages of vertebrates, although further functional studies are required to confirm this.

Pronounced expression of extracellular matrix proteoglycans regulated by Wnt pathway underlies the parallel evolution of lip hypertrophy in East African cichlids

“…There are hundreds of endemic cichlid species in the East African Great Lakes, Victoria, Malawi, and Tanganyika, as a result of explosive adaptive radiation (Salzburger, 2018; Santos et al, 2023). As a result of independent adaptations in each lake, parallel evolution is often observed among lakes, such as that of the nose snout (Duenser et al, 2023), jaw morphology, and body shape (Kocher et al, 1993; Muschick et al, 2012). To reveal their evolutionary mechanisms, genetic bases of the phenotypes have been investigated.…”