Every species has orphan genes that have no homologs in other species. This schematic shows the genome of the fruit fly (bottom) and the genome of an ancestor of the fruit fly (top). Each panel also shows (from left to right): genes that are highly conserved and can be traced back to prokaryotic organisms (yellow background); genes that are found in just a few related species (taxonomically restricted genes), orphan genes and potential orphan genes that are not currently expressed and are thus free from selection pressure (proto-orphan genes); and regions of the genome that do not code for proteins (blue background) (Van Oss and Carvunis, 2019; Palmieri et al., 2014). An orphan gene can form through the rapid divergence of the coding sequence (CDS) of an existing gene (1), or arise de novo from regions of the genome that do not code for proteins (including the non-coding parts of genes that evolve to code for proteins; 2). Some orphan genes will be important for survival, and will thus be selected for and gradually optimized (3). This means that the genes in a single organism will have a gradient of ages (Tautz and Domazet-Lošo, 2011). Many proto-orphan genes will undergo pseudogenation (that is, they will not be retained; 4). Coding sequences (shown as thick colored bars) with detectable homology are shown in similar colors. Vakirlis et al. estimate that a minority of orphan genes have arisen by divergence of the coding sequence of existing genes.