What makes us human?

Since ancient times, humans have wondered what makes us human. Different disciplines have sought answers to this endless question, and surely one of the most enticing proposals comes from biology, particularly genetics. Comparative biology is, in this sense, a very powerful tool that allows us not only to quantify the differences between species, but also to understand how these differences may have contributed to specific traits in our lineage. By comparing human genomes with closely related species with which we share a recent common origin, such as the great apes, we can identify which molecular changes are unique to humans and which we share with other primates. This evolutionary perspective helps us distinguish which traits are truly human and which are part of a deeper common heritage.

It has often been cited that only 1.24% of our genome separates humans from chimpanzees. However, this percentage hides a more complex truth. This value was calculated more than twenty years ago, based on a partial comparison of the most easily identifiable regions between the two genomes, and only one type of mutation was counted (single-nucleotide changes). Therefore, it was, as stated in the article, the lowest and most conservative number of differences between humans and chimpanzees.

But the biology of the two species is too different to be explained by such a small number. The quality of the genomes did not allow for the study of other, more difficult genomic regions and other types of mutations such as repeats, duplicated structures, insertions, or deletions. Now, thanks to recent advances in sequencing and the global effort to complete high-quality reference genomes, we are beginning to see a more complete picture.

From a single human gene to a network of accumulated changes

Recently, an international article generated and analyzed genomes of unprecedented quality from great apes, including chimpanzees, bonobos, gorillas, and orangutans, and compared them to the human genome. This allows us to revisit precisely these kinds of questions. Today we know that if we count all the genomic regions—both easy and difficult—the difference between the human and chimpanzee genomes is above 10%, not the 1% we all had in mind. This figure includes insertions, deletions, duplications, and other structural changes beyond simple nucleotide substitutions, but it still contains inaccuracies due precisely to the difficulty of knowing how to count these very complicated regions.

But beyond the percentage, these genomes will be the starting point for new studies that will allow us to address the global question of what makes us human. The analysis of these genomes has already revealed more than a million complex (structural) variants, many of them specifically associated with our species, which affect genes involved in neuronal, immunological, and reproductive processes. Furthermore, the study once again demonstrates that regions with high duplication rates are key sites of large-scale genomic innovation. Technological progress is thus leading us toward a new era in which we no longer search for a single "human gene" to explain our uniqueness, but rather a network of accumulated changes, both small and large, that have separated us evolutionarily and that demonstrate, once again, that the more we can understand our evolutionary relatives, the better we understand each other.