The polyploidy of Coffea arabica is an important trait affecting the evolution of this species. Genetic variability is scarce due to its recent origin as an interspecific hybrid from a single successful crossing event between Coffea canephora and Coffea eugenioides relatives. To further investigate the genomic composition of an allotetraploid we coupled high-throughput methodologies of co-expression analysis and full-length protein coding genes inference. Many of the expected orthologs were found to be missing from one of the two homoeologous chromosomes. The gene expression machinery is mainly represented by single-copy essential orthologs located in the Coffea eugenioides sub-genome. This result suggests a preference of the transcriptional and RNA processing machinery to be regulated by one parental sub-genome. To understand the operational modules of the sub-genomes transcription, we performed co-expression analysis that revealed 23 co-regulated modules. This system-wide approach clarified how biological processes (i.e., photosynthesis, cell wall biogenesis, translation, transcription, catabolism and biosynthesis) are running in synchrony and reinforces that there is an ongoing selective pressure in C. arabica that constrains the number of copies of some universal orthologues. Thus, this work contributes to our understanding of genome evolution in recent polyploids and supports crop breeding programs.