The mouse, being small, hardy, and a rapid breeder, has become the foremost model organism for experimental studies of vertebrate molecular genetics. Many naturally occurring mutations are known, often mimicking the effects of corresponding mutations in humans (Figure 1–46). Methods have been developed, moreover, to test the function of any chosen mouse gene, or of any noncoding portion of the mouse genome, by artificially creating mutations in it, as we explain later in the book.
Just one made-to-order mutant mouse can provide a wealth of information for the cell biologist. It reveals the effects of the chosen mutation in a host of different contexts, simultaneously testing the action of the gene in all the different kinds of cells in the body that could in principle be affected.
As humans, we have a special interest in the human genome. We want to know the full set of parts from which we are made, and to discover how they work. But even
Figure 1–44 Zebrafish as a model for studies of vertebrate development. These small, hardy tropical fish are convenient for genetic studies. Additionally, they have transparent embryos that develop outside of the mother, so that one can clearly observe cells moving and changing their character in the living organism throughout its development. (A) Adult fish. (B) An embryo 24 hours after fertilization. (A, with permission from steve Baskauf; B, from m. Rhinn et al., Neural Dev. 4:12, 2009.)
Figure 1–45 Times of divergence of different vertebrates. The scale on the left shows the estimated date and geological era of the last common ancestor of each specified pair of animals. each time estimate is based on comparisons of the amino acid sequences of orthologous proteins; the longer the animals of a pair have had to evolve independently, the smaller the percentage of amino acids that remain identical. The time scale has been calibrated to match the fossil evidence showing that the last common ancestor of mammals and birds lived 310 million years ago.
The figures on the right give data on protein—the α chain of hemoglobin. note that although there is a clear general trend of increasing divergence with increasing time for this protein, there are irregularities that are thought to reflect the action of changes of hemoglobin sequence when the organisms experienced special physiological demands. some proteins, subject to stricter functional constraints, evolve much more slowly than hemoglobin, time in millions of years others as much as five times faster. All this gives rise to substantial uncertainties in estimates of divergence times, and some experts believe that the major groups of mammals diverged from one another as if you were a mouse, preoccupied with the molecular biology of mice, humans would be attractive as model genetic organisms, because of one special property: through medical examinations and self-reporting, we catalog our own genetic (and other) disorders. The human population is enormous, consisting today of some 7 billion individuals, and this self-documenting property means that a huge database of information exists on human mutations. The human genome sequence of more than 3 billion nucleotide pairs has been determined for thousands of different people, making it easier than ever before to identify at a molecular level the precise genetic change responsible for any given human mutant phenotype.
By drawing together the insights from humans, mice, fish, flies, worms, yeasts, plants, and bacteria—using gene sequence similarities to map out the correspondences between one model organism and another—we are enriching our understanding of them all.
much as 60 million years more recently than shown here. (Adapted from s. kumar and s.B. hedges, Nature 392:917–920, 1998. With permission from macmillan Publishers ltd.)
Figure 1–46 Human and mouse: similar genes and similar development. The human baby and the mouse shown here have similar white patches on their foreheads because both have mutations in the same gene (called Kit), required for the development and maintenance of pigment cells. (courtesy of R.A. Fleischman.)