We can all imagine situations where an extra set of eyes might come in handy: eyeing members of the opposite sex while still paying attention to the professor during lecture, looking both ways at the same time before crossing the street; or watching your backside in a barroom brawl. How- ever useful extra eyes might be, creating them at selected locations is no simple matter. An eye is, after all, an exceed- ingly complex structure, consisting of photoreceptors, lens, nerves, and other tissues. It would be very unlikely for all of these structures to develop at a site where eyes don\u2019t normally exist. Nevertheless, in 1995, a group of geneticists succeeded in genetically engineering fruit \ufb02ies with extra eyes on their wings, legs, and antennae. How was this amaz- ing feat accomplished?

System
Immunoglobulin Structure
The Generation of Antibody Diversity
T-Cell-Receptor Diversity
Major Histocompatibility Complex

The Nature of Cancer
Cancer As a Genetic Disease
Genes That Contribute to Cancer
The Molecular Genetics of Colorectal

In 1993, Walter Gehring and his collaborators were investigatingDrosophila genes that encode transcription fac- tors (see Chapter 13). One of these genes mapped to the same location as that of thee yeless gene and, in fact, turned out to

development, Gehring\u2019s group genetically engineered cells that expressed thee yeless gene in parts of the \ufb02y where the gene is not normally expressed. When these \ufb02ies hatched, they had huge eyes on their wings, antennae, and legs. These struc- tures were not just tissue that resembled eyes; they were com- plete eyes with a cornea, cone cells, and photoreceptors that

responded to light, although the \ufb02ies could not use them to see, because they were not connected to the nervous system. Thee yeless gene appears to be one of the long-sought master control switches of development: its protein activates a set of other genes that are responsible for making a complete eye.

Thee yeless gene has counterparts in mice and humans that affect the development of mammalian eyes. There is a striking similarity between thee yeless gene ofDrosophila and the Small eye gene that exists in mice. In mice, a mutation in one copy ofSmall eye causes small eyes; a mouse that is homozygous for the Small eye mutation has no eyes. There is also a similarity between thee yeless gene inDrosophila and the

severely malformed human eye. Similarities in the sequences ofeyeless, Small eye, andAnir idia suggest that all three genes evolved from a common ancestral sequence. This possibility is surprising, because the eyes of insects and mammals were thought to have evolved independently. Similarities among

This chapter focuses on three specialized topics in genetics: developmental genetics, immunogenetics, and can- cer genetics. We begin with a discussion of the genetic control of the early development ofDrosophila embryos, one of the best-understood developmental systems. We then turn to the genetics of the immune system in vertebrates. This system is capable of generating proteins that recognize virtually any foreign substance in the body. The generation of this huge diversity of proteins relies on a special type of genetic recom- bination unique to the immune system. Last, we consider the genetic basis of cancer and how mutations in particular types of genes contribute to the growth of tumors in humans.

Every multicellular organism begins life as a unicellular, fer- tilized egg. This single-celled zygote undergoes repeated cell divisions, eventually producing millions or trillions of cells

that constitute a complete adult organism. Initially, each cell in the embryo istot ip otent \u2014 it has the potential to develop into any cell type. Many cells in plants and fungi remain totipotent, but animal cells usually become committed to developing into speci\ufb01c types of cells after just a few early embryonic divisions. This commitment often comes well before a cell begins to exhibit any characteristics of a partic- ular cell type; once the cell becomes committed, it cannot reverse its fate and develop into a different cell type. A cell becomes committed by a process calleddeter minat ion, the mechanism of which is still unknown.

For many years, the work of developmental biologists was limited to describing the changes that take place in the course of development, because techniques for probing the intracellular processes behind these changes were unavail- able. But, in recent years, powerful genetic and molecular techniques have had a tremendous in\ufb02uence on the study of development. In a few model systems such asD ros ophila, the molecular mechanisms underlying developmental change are now beginning to be understood.

If all cells in a multicellular organism are derived from the same original cell, how do different cells types arise? One possibility is that, throughout development, genes might be selectively lost or altered, causing different cell types to have different genomes. Alternatively, each cell might contain the same genetic information, but different genes might be expressed in each cell type. Early cloning experiments helped to answer this question.

In the 1950s, Frederick Steward developed methods for cloning plants. He disrupted phloem tissue from the root of a carrot, separating and isolating individual cells. He then placed individual cells in a sterile medium that contained nutrients. Steward was successful in getting the cells to grow and divide, and eventually he obtained whole edible carrots from single cells ( FIGURE 21.1). Because all parts of the plant were regenerated from a specialized phloem cell,

in a nutritive medium that contains growth hormones\u2026

Steward concluded that each phloem cell contained the genetic potential for a whole plant; none of the original genetic material was lost during determination.

The results of later studies demonstrated that most ani- mal cells also retain a complete set of genetic information during development. In 1952, Robert Briggs and Thomas King removed the nuclei from unfertilized oocytes of the frog

(an early embryonic stage) and injected these nuclei individ- ually into the oocytes. The eggs were then pricked with a needle to stimulate them to divide. Although most were dam- aged in the process, a few eggs developed into complete tad- poles that eventually metamorphosed into frogs.

In the late 1960s, John Gurdon used these methods to successfully clone a few frogs with nuclei isolated from intestinal cells of tadpoles. This accomplishment suggested that the differentiated intestinal cells carried the genetic information necessary to encode traits found in all other cells. However, Gurdon\u2019s successful clonings may have resulted from the presence of a few undifferentiated stem cells in the intestinal tissue, which were inadvertently used as the nuclei donors.

In 1997, researchers at the Roslin Institute of Scotland announced that they had successfully cloned a sheep by using the genetic material from a differentiated cell of an adult animal. To perform this experiment, they fused an udder cell from a white-faced Finn Dorset ewe with an enu- cleated egg cell and stimulated the egg electrically to initiate development. After growing it in the laboratory for a week, they implanted the embryo into a Scottish black-faced sur- rogate mother. Dolly, the \ufb01rst mammal cloned from an adult cell, was born on July 5, 1996( FIGURE21.2). Since

These cloning experiments demonstrated that genetic material is not lost or permanently altered during develop- ment \u2014 development must require the selective expression of genes. But how do cells regulate their gene expression in a coordinated manner to give rise to a complex, multicellu- lar organism? Research has now begun to provide some answers to this important question.

The ability to clone plants and animals from single
specialized cells demonstrates that genes are not
lost or permanently altered during development.

One of the best-studied systems for the genetic control of pattern formation is the early embryonic development ofDrosophila melanogaster. Geneticists have isolated a large number of mutations in fruit flies that influence all aspects of their development, and these mutations have been subjected to molecular analysis, providing much information about how genes control early development inD ro s o p h i l a .

\ufb01rst thoracic segment carries a pair of legs; the second tho- racic segment carries a pair of legs and a pair of wings; and the third thoracic segment carries a pair of legs and the halteres (rudiments of the second pair of wings found in most other insects). The abdomen contains nine segments.

When aDrosophila egg has been fertilized, its diploid nucleus ( FIGURE 21.4a) immediately divides nine times without division of the cytoplasm, creating a single, multinu- cleate cell ( FIGURE 21.4b). These nuclei are scattered throughout the cytoplasm but later migrate toward the periphery of the embryo and divide several more times

and around each nucleus, creating a layer of approximately 6000 cells at the outer surface of the embryo ( FIGURE21.4d). Four nuclei at one end of the embryo develop into pole cells, which eventually give rise to germ cells. The early embryo then undergoes further development in three distinct stages: (1) the anterior\u2013posterior axis and the dorsal\u2013ventral axis of the embryo are established ( FIGURE 21.5a); (2) the num- ber and orientation of the body segments are determined