## 2 Results
### Co-Expression Networks of Genes Involved in AsA Metabolism in Flavedo and Pulp of Fruits  
To decipher common regulation mechanisms of genes of the AsA metabolic pathways, a gene co-expression network was built independently for the flavedo and pulp, using the expression data at the different developmental stages (Figure 8A,C). Only significant correlations (Tables S1 and S2) were taken into account to build the networks, in which nodes represented the genes and edges represented positive and negative correlations between them. In addition, a similar analysis was carried out only taking into account the significant correlations between AsA and DHA concentrations and gene expression (Figure 8B,D, Tables S1 and S2). This analysis could not be performed for petals and leaves, since only two developmental stages were analyzed, not allowing a reliable and robust statistical analysis. Gene co-expression analysis showed that all the genes analyzed (23) were present in both the flavedo and pulp networks, but the number of links between genes was different in the two tissues (Figure 8A,C). Connections in the pulp were higher than in the flavedo, with a media of 8.5 edges in the pulp (98 in total) versus 5.0 in the flavedo (57 in total), indicating that genes seemed to be more co-expressed in the pulp. The architecture of the networks was similar and displayed two main groups with some interrelated genes. In the smaller group, the network comprised almost exclusively of genes belonging to the biosynthetic and recycling pathways, while in the larger group there where genes involved in AsA biosynthesis, recycling, and also degradation. Nonetheless, not all the genes present in the smaller group in the flavedo were present in the same group in the pulp and vice versa. In the flavedo, 15 genes showed a number of links above the media (_MDHAR2_, _APX2_, _GalUR14_, _DHAR2_, _GPP_, _GalUR8_, _GalUR12_, _APX1_, _MDHAR1_, _MDHAR3_, _DHAR1_, _GMP_, _GalDH_, _GalUR10_, and _APX4_) with most of them belonging to the degradation and recycling pathways. In the pulp, 11 genes had connections above the media (_GalDH_, _APX1_, _GalUR5_, _GalUR10_, _GalUR12_, _GalUR17_, _APX3_, _DHAR1_, _GME_, _AO_, and _MIOX_), belonging mainly to the biosynthetic pathways. Interestingly, four genes showed a high number of connections in both tissues: _APX1_, _DHAR1_, _GalUR10_, and _GalUR12_. Another similarity between tissues was that most of the connections among genes in both the flavedo and the pulp were positive, although a higher proportion of total correlations were negative in the flavedo. In particular, the recycling gene _DHAR1_ shared a high number of negative links with other genes in the flavedo, indicating a distinct expression pattern of this gene in the flavedo. The expression of this gene was high during the early stages of development and decreased at the beginning of maturation, only to increase again in more mature fruits. In the pulp, _APX2_ was the gene with the higher number of negative correlations, mainly to biosynthetic genes but also to genes involved in the degradation of AsA. Interestingly, _DHAR1_ was strongly and negatively correlated to _APX2_ in both tissues, indicating that these genes have contrasting expression patterns during maturation in both tissues. The largest group of genes interconnected in both tissues was _DHAR2_, _MDHAR1_, _MDHAR2_, _GalUR8_, _GalUR14_, and _GalLDH_, although these last two  
Figure 8: Gene co-expression networks of genes involved in the ascorbic acid (AsA) metabolism in the flavedo (**A**) and pulp (**C**) of Valencia Late orange (_Citrus sinensis_) fruit, and gene-metabolite correlation networks of AsA and DHA contents and the expression of AsA metabolic genes in the flavedo (**B**) and pulp (**D**).