Gene gain and loss shape both proteomes and the networks they form. The increasing availability of closely related sequenced genomes and of genome-wide network data should enable a better understanding of the evolutionary forces driving gene gain, gene loss and evolutionary network rewiring. Using orthology mappings across 23 ascomycete fungi genomes, we identified proteins that were lost, gained or universally conserved across the tree, enabling us to compare genes across all stages of their life-cycle. Based on a collection of genome-wide network and gene expression datasets from baker's yeast, as well as a few from fission yeast, we found that gene loss is more strongly associated with network and expression features of closely related species than that of distant species, consistent with the evolutionary modulation of gene loss propensity through network rewiring. We also discovered that lost and gained genes, as compared to universally conserved "core" genes, have more regulators, more complex expression patterns and are much more likely to encode for transcription factors. Finally, we found that the relative rate of network integration of new genes into the different types of networks agrees with experimentally measured rates of network rewiring. This systems-level view of the life-cycle of eukaryotic genes suggests that the gain and loss of genes is tightly coupled to the gain and loss of network interactions, that lineage-specific adaptations drive regulatory complexity and that the relative rates of integration of new genes are consistent with network rewiring rates.