Protein–protein interaction network module changes associated with the vertebrate fin-to-limb transition

Abstract

Evolutionary phenotypic transitions, such as the fin-to-limb transition in vertebrates, result from modifications in related proteins and their interactions, often in response to changing environment. Identifying these alterations in protein networks is crucial for a more comprehensive understanding of these transitions. However, previous research has not attempted to compare protein–protein interaction (PPI) networks associated with evolutionary transitions, and most experimental studies concentrate on a limited set of proteins. Therefore, the goal of this work was to develop a network-based platform for investigating the fin-to-limb transition using PPI networks. Quality-enhanced protein networks, constructed by integrating PPI networks with anatomy ontology data, were leveraged to compare protein modules for paired fins (pectoral fin and pelvic fin) of fishes (zebrafish) to those of the paired limbs (forelimb and hindlimb) of mammals (mouse). This also included prediction of novel protein candidates and their validation by enrichment and homology analyses. Hub proteins such as shh and bmp4, which are crucial for module stability, were identified, and their changing roles throughout the transition were examined. Proteins with preserved roles during the fin-to-limb transition were more likely to be hub proteins. This study also addressed hypotheses regarding the role of non-preserved proteins associated with the transition.