Gene Action 



163 



istence of symmetrically abnormal animals 

 is evidence of presence of penetrance of de- 

 velopmental action on both sides. Since the 

 developmental mechanism which brings 

 about an eye defect or absence of a bristle 

 on one side is independent of that which 

 acts on the other side it is not surprising that 

 the phenomenon of variable penetrance often 

 leads to phenotypic asymmetries. 



Sometimes the two types of right-left and 

 left-right asymmetries do not occur with 

 equal frequency, as for instance in harelip 

 and cleft palate in man (Fogh- Andersen, 

 '43). The genetic constitutions which under- 

 lie these abnormalities often are not pene- 

 trant, so that some individuals may appear 

 fully normal. Some other individuals show a 

 bilateral defect but in the majority the de- 

 fect is asymmetrical, occurring either on the 

 right or left side. Among the asymmetrical 

 individuals those with left harelip or cleft 

 palate are two to three times as frequent as 

 those with right defects. No specific explana- 

 tion can be given for this preference. In a 

 general way it is, however, obvious that the 

 typical asymmetry of the human embryo fur- 

 nishes internal environmental differences be- 

 tween the left and right side and that it is 

 not surprising if the variable penetrance of 

 the harelip-cleft palate genotypes responds 

 developmentally to these differences. It might 

 well be that cases exist where a mechanism 

 of variable penetrance always responds to 

 the basic asymmetry by showing an effect on 

 one specific side and never on the other. 

 However, no well established example seems 

 to be known. 



Some types of inherited asymmetries can- 

 not easily be interpreted by the hypothesis 

 of variable penetrance, which rests heavily 

 on the observation of symmetrically affected 

 and symmetrically nonaffected individuals 

 side by side with the asymmetrical ones. The 

 clearest divergent case is that of an asym- 

 metrical spotting pattern in the beetle 

 Bruchus quadrimaculatus (Breitenbecher, 

 '25). The normal females possess two black 

 spots bilaterally located on each elytrum, 

 but in a recessive mutant strain the females 

 have two black spots on one elytrum and 

 two red ones on the other. The asymmetry is 

 present in all individuals of the relevant 

 genotype but the two types "black spots at 

 right, red spots at left" and vice versa, are 

 not fixed — half of the females belong to one 

 and half to the other type regardless of the 

 phenotype of their ancestors. Breitenbecher 

 suggested that "probably some delicately ad- 

 justing mechanism shifts this asymmetry 



right or left according to chance." Dahlberg 

 ('43 and earlier) has elaborated a hypothesis 

 according to which in the cells of the em- 

 bryo "a particular gene may promote un- 

 equal distribution of cytoplasmatic material 

 without deciding the orientation of the dis- 

 tribution in a specified relation to particular 

 morphological axes. . . . The result is to dif- 

 ferentiate one cell lineage with an excess 

 from a second with a deficiency of the in- 

 clusion." If an excess inclusion or its de- 

 ficiency is decisive in determining the 

 manifestation of a phenotypic trait, as for 

 instance, position of pigmentation in Bruchus, 

 an explanation of its always asymmetrical 

 presence is provided. Dahlberg suggests that 

 his hypothesis should even be applied to the 

 interpretation of asymmetries expressed by 

 traits which often occur also symmetrically. 

 Such an extension of the scheme seems un- 

 necessary at present. 



A unique situation of genetically caused 

 asymmetry is given by the position of the ex- 

 ternal male genitalia in D. melanogaster. 

 Several mutants have been found which cause 

 a rotation of the genitalia. "Rotated-penis," 

 for instance, consists of a counterclockwise 

 rotation, to a variable degree. This externally 

 appearing asymmetry in a typically sym- 

 metrically arranged system of parts is in 

 reality evidence of an approach to internal 

 symmetry which is absent in nonmutant 

 males. In a normal nonmutant male the ex- 

 ternal genitalia may be described as rotated 

 clockwise through 360 degrees as compared 

 with the position of the genitalia in the fe- 

 male. The rotation is not apparent externally 

 but is evidenced internally by a spiral coun- 

 terclockwise looping of the sperm duct about 

 the intestine. In the males of the mutant the 

 internal rotation is partly undone by coun- 

 ter-rotation of the external genitalia which 

 now appear in an abnormal, asymmetrical 

 side wise position, or upside-down (Bridges, 

 in Morgan, Sturtevant and Bridges, '29). 



The genetic determination of direction of 

 coiling in snails has been mentioned earlier 

 (p. 156). It would be tempting to speculate 

 on the causes of the two types of coiling in 

 terms of asymmetrical arrangements at the 

 molecular level! 



DIFFERENTIATION 



The most general problem related to ge- 

 netics and development is posed by the fact 

 of embryonic differentiation "in spite of" sup- 

 posedly equal genie endowment of the cells 

 of all differentiating parts of the embryo. A 



