SELECTIVE NEUTRALITY OF 6PGD ALLOZYMES IN E. COLI AND THE EFFECTS OF GENETIC BACKGROUND

Abstract

We have used gluconate-limited chemostats to study selective differences between isogenic strains of Escherichia coli K12 into which four naturally occurring alleles coding for allozymes of 6-phosphogluconate dehydrogenase (6PGD) had been transferred. The limit of detectability of selection with our procedures is a selection coefficient of 0.5%. In the normal E. coli K12 genetic background, all alleles are selectively neutral or nearly neutral. The absence of detectable selection does, however, depend on genetic background and on such environmental factors as cell density. In a genetic background containing a mutation that cuts off the alternative metabolic route for 6-phosphogluconate, selection between allozymes can be detected, and the selection is in the direction expected from the measured apparent Km values of the allozymes. Even when the alternative metabolic route is not blocked by mutation, one of the 6PGD allozymes has a detrimental, but density-dependent, interaction with a mutation conferring resistance to bacteriophage T5. In all cases, the observed selection is due to the allozymes themselves (or to associated regulatory elements), as the selection disappears when the chemostats are limited by a different carbon source (ribose plus succinate). Nevertheless, the four alleles do seem to be selectively neutral or nearly neutral in the normal E. coli K12 genetic background. Moreover, the distribution of allele frequencies in natural populations of E. coli is in accord with the expectations of selective neutrality. I am inclined to suspect that we see, at least in some [cases], variations which are of no service to the species, and which consequently have not been seized on and rendered definite by natural selection…. Variations neither useful nor injurious would not be affected by natural selection, and would be left either a fluctuating element, as perhaps we see in certain polymorphic species, or would ultimately become fixed…. We may easily err in attributing importance to characters, and in believing that they have been developed through natural selection;… many structures are now of no direct use to their possessors, and may never have been of any use to their progenitors…. [On the other hand,] we are much too ignorant in regard to the whole economy of any organic being to say what slight modifications would be of importance or not.