Almost 2,000 years ago, Aristotle approached biological research with the question: what is an animal? Revisited since then through numerous morphological studies that ultimately unveiled concepts such as animal body plans, differentiated organs and principles of developmental patterning, this question remains as vibrant today as it may have been in ancient Greece. Although not the first study to introduce the genetic level into this debate, landmark work by Domazet-Lošo and Tautz in 2010 provided a captivating holistic perspective of the evolutionary constraints governing animal body formation. By capturing transcriptomes across key developmental stages of the zebrafish, fly, mosquito and nematode worm life cycles, the authors had the perfectly timed idea to roughly quantify the evolutionary origin of all genes (orphan genes) that contribute to the developmental transcriptome of the respective species through a novel comparative method they referred to as genomic phylostratigraphy.

The key idea underlying genomic phylostratigraphy is simple and elegant. It assumes that if all proteins within the tree of life indeed share common descent, then protein sequence alignments may provide sufficient evidence to trace back the potential origination event of each individual protein-coding gene of an extant species. The actual novelty of their approach was to combine this organismal gene age information with experimental evidence of gene expression, meaning that for each developmental stage of the animal life cycle they could quantify the average evolutionary age of genes that contribute to the overall pool of mRNAs (transcriptome). Introduced as transcriptome age index (TAI), Domazet-Lošo and Tautz found that the evolutionarily oldest genes (lower TAI) are most active during the middle period of embryo formation where the basic animal body plan assembles. By contrast, younger genes (higher TAI) are most active at early and late stages of embryo development (as well as in later life-cycle stages).