Point Mutations 



197 



gous (wide) Bar (and wild-type otherwise). 

 Since the very short right arm of the X 

 is entirely heterochromatic, it is of no con- 

 cern here. Because each F, female is hetero- 

 zygous for two paracentric inversions, any 

 crossing over between the left arms of her 

 X's produces dicentric or acentric crossover 

 strands which fail to enter the gametic nu- 

 cleus (see Chapter 12). Accordingly. F, 

 females produce eggs having an X that is, 

 for our purposes, either completely maternal 

 (sc 81 B InS apr sc H ) or completely paternal 

 ( + ) in derivation. If this F, daughter 

 mates with her Base brothers, half of the 

 sons in the next generation (¥ 2 ) receive the 

 + maternal X, and half receive the Base 

 maternal X. So, if the progeny of a single 

 Fi female are examined, it is a simple matter 

 to detect the presence of both types of sons 

 among the more than 80 F 2 progeny usually 

 produced. Note that each wild-type F 2 son 

 carries an identical copy of the X which the 

 mother (the Fi female) received from her 

 father (the Pi male). Even when the sperm 

 used to form the Fi female carries an X- 

 linked recessive lethal mutant, the F: fe- 

 male usually survives because she carries 

 its -f- allele in her Base chromosome, Each 

 wild-type F L > son, however, carries this mu- 

 tant in hemizygous condition and usually 

 dies before adulthood, so that no wild-type 

 sons appear in F>. It becomes clear, then, 

 since an Fi female is formed by fertilization 

 with a wild-type X-carrying sperm, the ab- 

 sence of wild-type sons among her progeny 

 is proof that the particular P y sperm carried 

 a recessive lethal, X-linked mutant. 



Such a lethal mutant must have occurred 

 in the germ line after the fertilization that 

 produced the Pi male; he would not have 

 survived had it been present at fertilization. 

 It is unlikely that many of the X-linked 

 lethals detected in sperm originate very early 

 in development, for in this case a large por- 

 tion of the somatic tissue would also carry 

 the lethal and usually cause death before 



adulthood. Even when a few hundred sperm 

 from one male are tested, only one is usually 

 found to carry an X-linked recessive lethal 

 mutant. This indicates that most X-linked 

 lethals present in sperm involve only a very 

 small portion of the germ line. Occasion- 

 ally, however, the mutation occurs early 

 enough in the germ line so that several sperm 

 tested from the same male carry what proves 

 to be the same recessive lethal. 



When a thousand sperm from normal, un- 

 treated males are tested for X-linked reces- 

 sive lethals by means of a thousand separate 

 matings of Fj females, approximately two 

 of these matings are found to yield no wild- 

 type sons. This X-linked recessive lethal 

 mutation frequency of 0.2% is fairly typical 

 in D. melanogaster. For every 1000 r of 

 X rays to which the adult male is exposed, 

 approximately 3.1% more sperm are found 

 to carry X-linked recessive lethals (see Fig- 

 ure 13-3, for the similar frequency obtained 

 after exposure to fast electrons). 



When used as described, the Base tech- 

 nique detects only those recessive lethals 

 which kill before adulthood. Other reces- 

 sive lethals that produce wild-type adult 

 males which are sterile or die before they 

 can mate are not detected. No recessive 

 lethals are detected unless they are hemi- 

 zygous in the F 2 male, as mentioned. Since 

 a considerable number of X-linked mutants 

 whose hemizygous lethality is prevented by 

 genes normally present in the Y chromo- 

 some is known to occur, this group is 

 missed because each F 2 male is normally 

 provided with a Y chromosome. Suitable 

 modifications of the Base procedure can be 

 made to detect this special kind of Y-sup- 

 pressed recessive lethal. On the other hand, 

 the advantages and applications of the Base 

 technique as described are numerous. 



For example, the presence or absence of 

 wild-type males in F 2 is easily and objec- 

 tively determined. Since the recessive lethal 

 detected in F 2 is also carried by the hetero- 



