A Kiss of Deep Homology: Partial Convergence in the Genomic Basis of Hypertrophied Lips in Cichlid Fish and Human Cleft Lip

Abstract

The genomic loci generating both adaptive and maladaptive variation could be surprisingly predictable in deeply homologous vertebrate structures like lips. Variation in highly conserved vertebrate traits such as jaws and teeth in organisms as evolutionarily disparate as teleost fishes and mammals are known to be structured by the same genes. Likewise, hypertrophied lips that have evolved repeatedly in Neotropical and African cichlid fish lineages could share unexpectedly similar genetic bases themselves and even provide surprising insight into the loci underlying human craniofacial anomalies. To isolate the genomic regions underlying adaptive divergence in hypertrophied lips, we first employed genome wide associations (GWA) in several species of African cichlids from Lake Malawi. Then, we tested if these GWA regions were shared through hybridization with another Lake Malawi cichlid lineage that has evolved hypertrophied lips seemingly in parallel. Overall, introgression among hypertrophied lip lineages appeared limited. Among our Malawi GWA regions, one contained the gene kcnj16 that has been implicated in the convergently evolved hypertrophied lips in Central American Midas cichlids that diverged from the Malawi radiation over 50 million years ago. The Malawi hypertrophied lip GWA regions also contained several additional genes that cause human lip-associated birth defects. Cichlid fishes are becoming prominent examples of replicated genomic architecture underlying trait convergence and are increasingly providing insight into human craniofacial anomalies such as cleft lip.

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

“…Cichlid fishes have acquired a huge diversity in their oral morphologies, reflecting ecological and trophic specializations (Albertson and Kocher, 2006;Kocher, 2004;Lecaudey et al, 2021Lecaudey et al, , 2019. Hypertrophied lips, one of the most prominent examples of oral diversity, have been independently acquired in cichlids inhabiting each of the East African Great Lakes, as well as in the Nicaraguan crater lakes and South American rivers (Henning et al, 2017;Kautt et al, 2020;Masonick et al, 2023Masonick et al, , 2022. Several hypotheses have been proposed for the adaptive roles of hypertrophied lips, such as for effectively sucking prey out from narrow crevices (Lukas et al, 2015), reducing mechanical stress during foraging in rocky habitats (Fryer, 1972;Greenwood, 1974), and facilitating prey detection by providing an enlarged area for taste receptors (Arnegard and Snoeks, 2001;Oliver and Arnegard, 2010).…”

“…For example, transcriptome comparisons between hypertrophied and normal lips of cichlids in Lake Tanganyika (Colombo et al, 2013) and South American crater lakes (Manousaki et al, 2013) have identified some differentially expressed genes (DEGs) as candidates for lip hypertrophy; however, their primary regulators remain to be elucidated. In addition, quantitative trait locus (QTL) mapping (Henning et al, 2017) and genome-wide association study (GWAS) (Masonick et al, 2023) have been conducted to elucidate the genomic loci responsible for hypertrophied lips in the cichlids of Lake Victoria and Lake Malawi. These genome-wide studies concluded that lip hypertrophy was a polygenic trait involving several candidate genes.…”