Abstract
The rewiring of gene regulatory networks can generate phenotypic novelty. It remains an open question, however, how the large number of connections needed to form a novel network arise over evolutionary time. Here, we address this question using the network controlled by the fungal transcription regulator Ndt80. This conserved protein has undergone a dramatic switch in function-from an ancestral role regulating sporulation to a derived role regulating biofilm formation. This switch in function corresponded to a large-scale rewiring of the genes regulated by Ndt80. However, we demonstrate that the Ndt80-target gene connections were undergoing extensive rewiring prior to the switch in Ndt80's regulatory function. We propose that extensive drift in the Ndt80 regulon allowed for the exploration of alternative network structures without a loss of ancestral function, thereby facilitating the formation of a network with a new function.
Highlights
The emergence of novel traits has long fascinated evolutionary biologists, with many intriguing examples observed across the tree of life (Pigliucci, 2008; Rieppel, 2001; Shubin et al, 2009; Wagner and Lynch, 2010)
To distinguish between these models, we identified the genes directly regulated by Ndt80 in both S. cerevisiae and C. albicans using chromatin immunoprecipitation of epitope-tagged Ndt80
We identified genes with significant peaks of ChIP enrichment in their intergenic regions; this is our least stringent criteria. We filtered this set to include only those ChIP enrichment peaks that contained an Ndt80 cis-regulatory motif in the intergenic region. Of those ChIP peaks that contained an Ndt80 motif, we further refined the set of Ndt80 targets by requiring that the motif be present in the orthologous intergenic region of two very closely related species, as this greatly increases the likelihood that the Ndt80-binding site was maintained by selection. (For S. cerevisiae, we used S. mikatae and S. kudriavzevii, for C. albicans we used C. tropicalis and C. dubliniensis [Byrne and Wolfe, 2005; Lohse et al, 2013])
Summary
The emergence of novel traits has long fascinated evolutionary biologists, with many intriguing examples observed across the tree of life (Pigliucci, 2008; Rieppel, 2001; Shubin et al, 2009; Wagner and Lynch, 2010). It remains unclear how a large number of genes (whether old or new) can be brought together to form a new network To address these questions, we examined the evolutionary history of Ndt, a sequence-specific DNA-binding protein that is deeply conserved across a large group of fungal species encompassing approximately 300 million years of diversity. In the narrow lineage leading to the human fungal pathogen species Candida albicans, Ndt acquired a new role as a master regulator of the gene regulatory network that controls the formation of biofilms, multicellular communities of surfaceassociated cells (Figure 1A) (Nobile et al, 2012) This newly evolved trait enables C. albicans to persist on mucosal surfaces and on implanted medical devices (Bonhomme and d’Enfert, 2013; Kojic and Darouiche, 2004; Nobile et al, 2012) and is responsible for many of the disease-
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