Medicine treats diseases from two main causes: germs and genes. Epidemiology addresses the former, while embryology handles much of the latter. How can clinicians make sense of the zoo of genetic birth defects catalogued in the OMIM (Online Mendelian Inheritance in Man database) at NCBI (National Center for Biotechnology Information)? The counterintuitive answer, posited by the accompanying review article, is to consult fruit flies! It turns out that humans and flies share a common genetic scaffolding upon which their (obviously quite different) bodies are built during embryonic development. This scaffolding arose in our common ancestor ~500 million years ago.
The ABCs of our scaffolding entail Axes, Boundaries, and Coordinates. The three dimensions of our body (anterior-posterior, dorsal-ventral, and left-right) arise as a Cartesian coordinate system of x, y, and z axes. At one end of each axis a protein is secreted which diffuses to the other end. Curiously, those proteins are the very same growth factors (TGF-beta, Sonic Hedgehog, Fibroblast Growth Factor, etc.) that cause cancer in adults! Because signal intensity decreases with distance, cells can assess their position (coordinate) by measuring the concentration at their location. Those positions then dictate the boundaries between modular compartments such as vertebrae along our spine or fingers across our palm. Amazingly, the same ancient circuit of Homeobox genes partitions our spine into cervical, thoracic, lumbar, sacral, and coccygeal “area codes” on the one hand, and assigns the identities of our fingers (pinkie, ring, middle, index, thumb) on the other. (Overview provided by Lewis Held)
Abstract
The human body is one still frame in a very long evolutionary movie. Anthropologists focus on the last few scenes, whereas geneticists try to trace the screenplay back as far as possible. Despite their divergent time scales (millions versus billions of years), both disciplines share a reliance on a third field of study whose scope spans only a matter of days to months, depending on the organism. Embryology is crucial for understanding both the pliability of anatomy and the modularity of gene circuitry. The relevance of human embryology to anthropology is obvious. What is not so obvious is the notion that equally useful clues about human anatomy can be gleaned by studying the development of the fruit fly, an animal as different from us structurally as it is distant from us evolutionarily. The underlying kinship between ourselves and flies has only become apparent recently, thanks to revelations from the nascent field of evolutionary developmental biology, or evo-devo. All bilaterally symmetric animals, it turns out, share a common matrix of body axes, a common lexicon of intercellular signals, and a common arsenal of genetic gadgetry that evolution has tweaked in different ways in different lineages to produce a dazzling spectrum of shapes and patterns. Anthropologists can exploit this deep commonality to search our genome more profitably for the mutations that steered us so far astray from our fellow apes.
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