Analysis of central Hox protein types across bilaterian clades: On the origin of central Hox proteins from an Antennapedia/Hox7-like ancestor

TL;DR

This study uses bioinformatics and phylogenetics to classify central Hox proteins across bilaterian species, revealing seven sequence types and challenging existing classification schemes, thus shedding light on their evolutionary origins.

Contribution

It identifies seven distinct central Hox protein types and proposes a sequence-based classification approach over synteny-based schemes for better evolutionary understanding.

Findings

Seven central Hox protein sequence types identified

Only one type (Antp/Hox7) is conserved across all bilaterian clades

Sequence-based classification offers a more meaningful evolutionary framework

Abstract

Hox proteins are one of the best studied sets of transcription factors in developmental biology. They are major determinants for establishing morphological differences along the anterior-posterior axis of animals and are generally regarded as highly conserved in function. This view is based on experiments comparing a few (anterior) Hox proteins, however, the extent to which central or abdominal Hox proteins share sequence features or functions remains largely unexplored. To shed light on the origin and functional divergence of the central Hox proteins, we combine a powerful bioinformatics tool (CLANS) with a large-scale phylogeny of species. CLANS is used to differentiate between the various types of central Hox protein sequences, while the phylogeny provides an evolutionary context to the analysis. The combination of both enables us to infer the relative timepoint at which a given central Hox protein type arose. We identify seven distinct central Hox protein sequence types, only one of which is common to all protostome and deuterostome clades (Antp/Hox7). Together, these results lead us to suggest reevaluating the usefulness of the increasingly depicted synteny-based classification scheme that assumes a one-to-one orthology between protostome and deuterostome central Hox proteins. Instead, we propose that the use of sequence-based classification schemes able to resolve the central and posterior Hox proteins provides a more promising and biologically meaningful alternative to resolving these groups. This analysis, which provides a unique overview of the Hox protein sequence types present across protostomes and deuterostomes as well as a relative dating for the emergence of the central Hox protein types, provides a crucial clue to illuminate how and when the distinct developmental blueprints for organisms evolved within the evolutionarily immensely successful bilaterian lineage.