This Week's Citation Classic: Human Natural Selection

R.A. Fisher, Julian Huxley, and E.B Ford were members of a small clique British and American scholars who were the driving forces behind the "New Synthesis", the refinement and spread of Darwin's theory of evolution during the 1930's and 40's.

They can together also be counted as publishing the first ever test of the effects of natural selection on humans.

This week's citation classic is FISHER, R. A., E. B. FORD and J. HUXLEY, 1939 Taste-testing the anthropoid apes. Nature 144: 750.

You probably remember phenylthiocarbamide or PTC from Intro Biology or Genetics class. Those little strips of paper which, depending on your genotype, was either bitter or tasteless. Bitter for me.

PTC's unique attributes was first discovered by Arthur Fox in 1932 when he was pouring some of the powder and it flew into the air (aahh the days before the Lab Safety Officers). His co-worker C.A. Noller complained that the powder was bitter, yet Fox could taste nothing. Fox set about testing a large group of people and found that indeed they could be divided into tasters and non-tasters.

Fisher, Ford and Huxley realized that this could be a great opportunity to test theories regarding the origins of balanced polymorphisms and whether natural selection has acted upon human genes.

Fisher et al. wrote "in the course of discussions on the possibility that the blood-group frequencies found in man were determined by a balance of selective influences, it occurred to one of the authors that evidence on the parallel possibility for taste could be obtained by testing the anthropoid apes."

In what must have been an almost comic series of experiments, the three tested whether apes could taste PTC. One of the apes took a strong dislike to Fisher and "and spat at him and even tried to grab him". But the trio succeeded in measuring PTC sensitivity for all apes, "excepting one chimpanzee, which was too shy".

The results were remarkable. Mendelian expectation for dominant and recessive genes suggests tasters should represent 3/4ths of the population and nontasters 1/4th. Of the 27 individuals tested, 20 were tasters and 7 were nontasters, implying allele frequencies of 49 and 51% for the taster and nontaster alleles, almost precisely as expected.

Fisher et al. write "Without the conditions of stable equilibrium it is scarcely conceivable that the gene - ratio should have remained the same over the million or more generations which have elapsed since the separation of the anthropoid and hominid stocks. The remarkable inference follows that over this period the heterozygotes for this apparently valueless character have enjoyed a selective advantage over both the homozygotes, and this, both in the lineage of the evolving chimpanzees and in that of evolving man. Wherein the selective advantages lie, it would at present be useless to conjecture, but of the existence of a stably balanced and enduring dimorphism determined by this gene there can be no room for doubt."

Fig. Hypotheses for the origin of PTC taster and nontaster alleles. (Left) FISHER et al.'s (1939) "Single Origin" hypothesis. Under this hypothesis, the taster (T) and nontaster (t) alleles diverged prior to the human–chimpanzee species divergence. Then both alleles were maintained separately in each species up to the present time. The maintenance of both alleles for such an extended period [FISHER (1939b) thought that it must be 1 million generations, or 20–30 million years] is unlikely if balancing selection has not been active because one allele or the other would be expected to go to fixation. (Right) WOODING et al.'s (2006) "Separate Origin" hypothesis. Under this hypothesis, nontaster alleles were derived from taster alleles twice—once in each species—after the human–chimpanzee species divergence. Arrows indicate divergence events.

The biological significance of the polymorphism was not clear to Fisher et al. nor was it identified until quite recently. Long story short is that the non-taster allele is not non-functional. On the contrary it appears to provide the non-PTC taster with the ability to taste other compounds that the PTC taster cannot taste.

Evidence that the TAS2R38 nontaster allele is functional suggests an immediate mechanism through which heterozygote advantage might arise at this locus. If the taster allele confers sensitivity to PTC and its chemical relatives, and the nontaster allele confers sensitivity to some other set of compounds, then heterozygotes should be able to taste both sets of compounds. Thus, they might garner a fitness advantage by being able to regulate the intake of a greater diversity of bitter compounds than can homozygotes. Wooding 2006.

A final point is that the parsimonious hypothesis that the PTC allele arose once has been refuted.

Taken together, the findings of WOODING et al. (2006) support FISHER et al.'s (1939) finding that both humans and chimpanzees harbor taster and nontaster alleles and that these alleles are found at similar frequencies in each species; however, they reject the hypothesis that these alleles were derived once, prior to the human–chimpanzee divergence. Rather, the nontaster alleles, which confer their phenotypic effects through entirely different molecular mechanisms, appear to have twice evolved independently. The details of the selective pressures underlying this more complex process remain a matter of conjecture. Wooding 2006.

This post was largely derived from Wooding 2006.

Photo: (Left to right) R. A. Fisher, E. B. Ford, and Julian Huxley. Portraits are from YATES and MATHER (1963), CLARKE (1995), and BAKER (1976).