Many Genes Controlling Development Are Remarkably Similar in Humans and Other Animals

As humans, we probably have a biased and somewhat exaggerated view of our status in the animal kingdom. Pride in our swollen forebrain and its associated mental capabilities may blind us to the remarkably sophisticated abilities of other species: navigation by birds, the sonar system of bats, homing by salmon, or the flight of a fly.

Despite all the evidence for evolutionary unity at the cellular and physiological levels, everyone expected that genes regulating animal development would differ greatly from one phylum to the next. After all, insects and sea urchins and mammals look so different. We must have many unique proteins to create a brain like ours . . . or must we? The fruits of research in developmental genetics during the past two decades reveal that insects and mammals, which have a common ancestor about half a billion years ago, possess many similar development-regulating genes (Figure 1-26). Indeed, a large number of these genes appear to be conserved in many and perhaps all animals. Remarkably, the developmental functions of the proteins encoded by these genes are also often preserved. For instance, certain proteins involved in eye development in insects are related to protein regulators of eye development in mammals. Same for development of the heart, gut, lungs, and capillaries and for placement of body parts along the head-to-tail and back-to-front body axes (Chapter 15).

M FIGURE 1-26 Similar genes, conserved during evolution, regulate many developmental processes in diverse animals.

Insects and mammals are estimated to have had a common ancestor about half a billion years ago. They share genes that control similar processes, such as growth of heart and eyes and organization of the body plan, indicating conservation of function from ancient times. (a) Hox genes are found in clusters on the chromosomes of most or all animals. Hox genes encode related proteins that control the activities of other genes. Hox genes direct the development of different segments along the head-to-tail axis of many animals as indicated by corresponding colors. Each gene is activated (transcriptually) in a specific region along the head-to-toe axis and controls the growth of tissues there. For example, in mice the Hox genes are responsible for the distinctive shapes of vertebrae. Mutations affecting Hox genes in flies cause body parts to form in the wrong locations, such as legs in lieu of antennae on the head. These genes provide a head-to-tail address and serve to direct formation of the right structures in the right places. (b) Development of the large compound eyes in fruit flies requires a gene called eyeless (named for the mutant phenotype). (c) Flies with inactivated eyeless genes lack eyes. (d) Normal human eyes require the human gene, called Pax6, that corresponds to eyeless. (e) People lacking adequate Pax6 function have the genetic disease aniridia, a lack of irises in the eyes. Pax6 and eyeless encode highly related proteins that regulate the activities of other genes, and are descended from the same ancestral gene. [Parts (a) and (b) Andreas Hefti, Interdepartmental Electron Microscopy (IEM) Biocenter, University of Basel. Part (d) © Simon Fraser/Photo Researchers, Inc.]

This is not to say that all genes or proteins are evolution-arily conserved. Many striking examples exist of proteins that, as far as we can tell, are utterly absent from certain lineages of animals. Plants, not surprisingly, exhibit many such differences from animals after a billion-year separation in their evolution. Yet certain DNA-binding proteins differ between peas and cows at only two amino acids out of 102!

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