The Barrettâs Gland in Phenotype SpaceSummary

Barrettâs esophagus is characterized by the erosive replacement of esophageal squamous epithelium by a range of metaplastic glandular phenotypes. These glandular phenotypes likely change over time, and their distribution varies along the Barrettâs segment. Although much recent work has addressed Barrettâs esophagus from the genomic viewpointâits genotype spaceâthe fact that the phenotype of Barrettâs esophagus is nonstatic points to conversion between phenotypes and suggests that Barrettâs esophagus also exists in phenotype space. Here we explore this latter concept, investigating the scope of glandular phenotypes in Barrettâs esophagus and how they exist in physical and temporal space as well as their evolution and their life history. We conclude that individual Barrettâs glands are clonal units; because of this important fact, we propose that it is the Barrettâs gland that is the unit of selection in phenotypic and indeed neoplastic progression. Transition between metaplastic phenotypes may be governed by neutral drift akin to niche turnover in normal and dysplastic niches. In consequence, the phenotype of Barrettâs glands assumes considerable importance, and we make a strong plea for the integration of the Barrettâs gland in both genotype and phenotype space in future work. Keywords: Barrettâs Esophagus, Neutral Drift, Metaplasi