Coelimination and Survival in Gene Network Evolution: Dismantling the RA-Signaling in a Chordate

Abstract

<p class="first" id="d6376027e168">The bloom of genomics is revealing gene loss as a pervasive evolutionary force generating genetic diversity that shapes the evolution of species. Outside bacteria and yeast, however, the understanding of the process of gene loss remains elusive, especially in the evolution of animal species. Here, using the dismantling of the retinoic acid metabolic gene network (RA-MGN) in the chordate <i>Oikopleura dioica</i> as a case study, we combine approaches of comparative genomics, phylogenetics, biochemistry, and developmental biology to investigate the mutational robustness associated to biased patterns of gene loss. We demonstrate the absence of alternative pathways for RA-synthesis in <i>O. dioica</i>, which suggests that gene losses of RA-MGN were not compensated by mutational robustness, but occurred in a scenario of regressive evolution. In addition, the lack of drastic phenotypic changes associated to the loss of RA-signaling provides an example of the inverse paradox of Evo–Devo. This work illustrates how the identification of patterns of gene coelimination—in our case five losses ( <i>Rdh10</i>, <i>Rdh16</i>, <i>Bco1</i>, <i>Aldh1a</i>, and <i>Cyp26</i>)—is a useful strategy to recognize gene network modules associated to distinct functions. Our work also illustrates how the identification of survival genes helps to recognize neofunctionalization events and ancestral functions. Thus, the survival and extensive duplication of <i>Cco</i> and <i>RdhE2</i> in <i>O. dioica</i> correlated with the acquisition of complex compartmentalization of expression domains in the digestive system and a process of enzymatic neofunctionalization of the <i>Cco</i>, while the surviving <i>Aldh8</i> could be related to its ancestral housekeeping role against toxic aldehydes. </p>