By Chuck Sanders
President-past of the Protein Society
The American holiday of Thanksgiving is my favorite. I am guessing that some of my friends from the Great White North share the same opinion about the Canadian version of this feast day, which occurs there in early October. Taking time to “count your blessings” for whatever good fortune you experience in life is, to me, enormously appealing. Moreover, Thanksgiving enjoys a protected status as a mostly uncorrupted holiday because it falls in between the over-the-top Halloween and Yuletide holidays.
In preparation for our big family-and-friends dinner later this week, my wife just pulled out her recipe box of culinary protocols for preparing Appalachian and Midwestern dishes from both sides of our family, plus some Betty Crocker classics we are not too proud to enjoy. I note with endless admiration that my wife is a really fine cook. My role in preparing Thanksgiving dinner mainly involves trying to stay out of her way until it is time to carve the turkey.
Cooking food is a human behavioral trait that sets us apart from other animals, including our closest extant relatives, the chimpanzees. The adoption of this practice likely came soon after hominins learned to manipulate fire. Playing with fire and eating cooked food introduced new selective evolutionary pressures on our ancestors (e.g., the need for burn wound-healing mechanisms), while relaxing others (e.g., large and powerful jaws were no longer needed for eating). This resulted in hard-wiring of adaptations into the hominin genome that have been passed on to modern humans. These sorts of changes in the human genome reflect the interplay between hominin culture and evolutionary trajectory—a form of gene-environment evolutionary coupling.
There appear to be over 600 defined traits that are not shared between humans and chimpanzees, the outcome of three to five million years of evolution since our last common ancestor. It is a great challenge for scientists to unravel the series of genomic variations that occurred during the several million years that led to the emergence of Homo sapiens. The fossil record has yielded much useful information regarding the timeline of hominin evolution, both about changes in body structure (e.g., increased brain cavity size) and the progressive sophistication of hominin culture (e.g., stone tools). Advances in DNA extraction, sequencing, and analysis are also providing glimpses of the genomes of archaic hominins (Neanderthals, for example). We can also compare the human genome to that of the chimpanzee.
The degree of sequence similarity between the human and chimp genomes, including non-coding segments, is on the order of 96 percent. For protein-encoding genes the level of sequence similarity is 99 percent, with 3,000 of 20,000 human proteins sharing an identical sequence with their chimp homologs. This does not mean sequence differences between human and chimp protein are all insignificant. The human FOXP2 transcription factor differs in sequence from its chimp homolog and is believed to play an important role in enabling human speech. Nevertheless, to the disappointment of reductionist protein scientists such as the author, it appears that most of the profound differences between the human and chimp genomes involve differences in genome organization, gene copy numbers, transcriptional regulation, DNA methylation and epigenetics. This includes the complete silencing of some protein-encoding genes through various mechanisms. A particularly intriguing example is the silencing via loss of an exon of the human gene encoding cytidine monophospho-N-acetylneuraminic acid hydroxylase (known as CMAH), an enzyme that produces a sialic acid derivative, N-glycolylneuraminic acid, or Neu5Gc. This results in loss of a form of sialic acid that is prominent in great ape glycobiology and profoundly alters the structures of numerous protein-attached complex glycosides in humans in ways that impact a wide variety of physiological, immunological, and biochemical processes—particularly in the brain. Despite this easy-to-grasp example, the genomic changes responsible for most human-specific traits remain mysterious. Much future effort will be required to reveal the mechanisms that have conferred humans with their most distinctive traits.
Among the most astounding of human traits is the capacity for symbolic, abstract, and creative analytical thinking. These unparalleled human traits have the capacity to generate their own selective evolutionary pressure. To cite an amusing example, humans have the ability to surmise what others think about them in a social setting. This is sometimes the basis for embarrassment. In turn, embarrassment is the trigger for an evolved physiological response that is unique to humans: blushing. This leads us back to the concept that environment—which includes culture—can alter evolutionary trajectories. Pascal Gagneux, Ajit Varki, and co-workers have considered this fact in the context of genetic differences between humans and chimps and suggested that the human genome is much more of a recipe box than it is a blueprint. What ends up in the box and how the recipes are changed, copied and then changed, or even discarded with time depends on a variety of environmental factors: What ingredients are locally available? Do adjustments need to be made to satisfy a particular craving? Does the food need to look pretty? Are their dietary restrictions?
It is a sobering matter that the human imagination and its aspirations—be they good or be they evil—can potentially be written up and deposited in the recipe box of life and then passed on from generation to generation. Ours is the only species that has the capacity to consciously and deliberately manipulate its own evolutionary trajectory.
May it be that the human traits each one of us helps to establish during our brief times here on earth will be counted as blessings by future generations!
Acknowledgements
I thank Becky Sanders for her edits. Much of the information conveyed in this article was derived from reading and re-reading a superb critical review by M-Vaill, K-Kawanishi, N-Varki, P-Gagneux, and A-Varki “Comparative Physiological Anthropogeny: Exploring Molecular Underpinnings of Distinctly Human Phenotypes” (Physiological Reviews 2023, 103, 2171-2229).