Pseudogenisation of NK3 Homeobox 2 (Nkx3.2) in Monotremes Provides Insight into Unique Gastric Anatomy and Physiology

Abstract

AbstractDevelopment of the vertebrate antral stomach and pyloric sphincter (antropyloric region) – involved in enzymatic breakdown and thoroughfare of food - is underpinned by a highly conserved developmental pathway involving the hedgehog, bone morphogenetic protein (BMP) and Wingless/Int-1 (Wnt) protein families. Monotremes are a unique lineage where acid-based digestion has been lost, and this correlates with a lack of genes for gastric acid and enzymes in the genomes of the platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus). Furthermore, these species feature unique gastric phenotypes, both with truncated and aglandular antral stomachs and the platypus with no pylorus. Here, we explore the genetic underpinning of monotreme gastric phenotypes, investigating genes important in antropyloric development using the newest monotreme genome sequences (mOrnAna1.pri.v4 and mTacAcu1) together with RNA-seq data. We found that the pathway is generally conserved but, NK3 homeobox 2 (Nkx3.2) was pseudogenised in both platypus and echidna. We speculate that pyloric-like restriction in the echidna may correlate with independent evolution ofGrem1andBmp4sequences, and that the convergent loss of gastric acid and stomach size genotypes and phenotypes in teleost and monotreme lineages may be a result of eco-evolutionary dynamics. These findings reflect the effects of gene loss on phenotypic evolution and further elucidate the genetic control of monotreme stomach anatomy and physiology.