In defence of the Milquetoast phenotype
Authors: Robert Beech
Journal: The Lancet (1999)

Hugh Montgomery and colleagues (Feb 13, p 541)1Montgomery H Clarkson P Barnard M et al.Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training.Lancet. 1999; 353: 541-544Summary Full Text Full Text PDF PubMed Scopus (200) Google Scholar describe a polymorphism in the angiotensinconverting enzyme gene, one allele of which (the insertion [I] allele) is associated with incroeased response to physical training. Individuals with the II genotype (homozygous for the I allele) had a greater anabolic response to physical conditioning and the I genotype was associated with the elite physical performance under hypoxic conditions.2Montgomery H Marshall R Hemingway H Myerson S Human gene for physical performance.Nature. 1998; 393: 221-222Crossref PubMed Scopus (464) Google ScholarThese findings raise an obvious evolutionary question, why does not everyone have this gene? After all, a gene that gives you bigger, stronger muscles for the same amount of work seems to be an obvious selective advantage. You can run away from predators, run after prey, and when it comes to reproductive fitness, a generously endowed set of biceps might render the results of the poetry competition moot.One possibility is that the deletion (D) allele, is an evolutionary newcomer, a disadvantageous mutation that is in the process of being selected out of the human genome. However, Montgomery and colleagues2Montgomery H Marshall R Hemingway H Myerson S Human gene for physical performance.Nature. 1998; 393: 221-222Crossref PubMed Scopus (464) Google Scholar state that “both groups [mountain climbers and controls] were in Hardy-Weinberg equilibrium”. This suggests that both alleles had been present in the population long enough to reach a stable equilibrium. If the D allele were a new deleterious mutation, there is no reason why it should increase in the population and thus reach a steady state. Alternatively, the I allele may be a new advantageous allele, which is gradually replacing the D allele, but then the two alleles should not be in Hardy-Weinberg equilibrium. The data thus seems to indicate that the presence of I versus D alleles is selectively neutral. This neutrality could be true either if the two alleles had no effect on fitness (from an evolutionary point of view), or if there were opposing effects from two different selective forces each of which acted to maintain a particular allele in the population. The classic example is the haemoglobin gene, in which HbS allele confers protection against malaria in the heterozygous state, but confers reduced lifespan and fertility in the homozygous state.With these seemingly obvious advantages of the I allele, what selective forces might act to maintain the D allele in the human population? One possibility is limited food availability. Although increased muscle mass (or more precisely, increased anabolic response to physical training) has clear advantages under several circumstances, it also requires a high energy intake to maintain that muscle mass. Faced with the situation of limited food supply there are at least two evolutionary strategies an organism can use. The first is to increase efforts to obtain food. The II genotype would seem to offer some advantages here, and when the going gets tough, the II bulk up and get tougher. An alternative strategy is to reduce muscle mass and thereby decrease the amount of food that needs to be gathered. When the going gets tough, the DD hunker down and hope for better times.Which strategy is better? Since the two alleles are in equilibrium, there must be selective pressures acting to maintain both alleles. Although we tend to think of evolution acting to enhance performance, this is not necessarily true. Evolution perpetuates strategies that work, for whatever reason. Hugh Montgomery and colleagues (Feb 13, p 541)1Montgomery H Clarkson P Barnard M et al.Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training.Lancet. 1999; 353: 541-544Summary Full Text Full Text PDF PubMed Scopus (200) Google Scholar describe a polymorphism in the angiotensinconverting enzyme gene, one allele of which (the insertion [I] allele) is associated with incroeased response to physical training. Individuals with the II genotype (homozygous for the I allele) had a greater anabolic response to physical conditioning and the I genotype was associated with the elite physical performance under hypoxic conditions.2Montgomery H Marshall R Hemingway H Myerson S Human gene for physical performance.Nature. 1998; 393: 221-222Crossref PubMed Scopus (464) Google Scholar These findings raise an obvious evolutionary question, why does not everyone have this gene? After all, a gene that gives you bigger, stronger muscles for the same amount of work seems to be an obvious selective advantage. You can run away from predators, run after prey, and when it comes to reproductive fitness, a generously endowed set of biceps might render the results of the poetry competition moot. One possibility is that the deletion (D) allele, is an evolutionary newcomer, a disadvantageous mutation that is in the process of being selected out of the human genome. However, Montgomery and colleagues2Montgomery H Marshall R Hemingway H Myerson S Human gene for physical performance.Nature. 1998; 393: 221-222Crossref PubMed Scopus (464) Google Scholar state that “both groups [mountain climbers and controls] were in Hardy-Weinberg equilibrium”. This suggests that both alleles had been present in the population long enough to reach a stable equilibrium. If the D allele were a new deleterious mutation, there is no reason why it should increase in the population and thus reach a steady state. Alternatively, the I allele may be a new advantageous allele, which is gradually replacing the D allele, but then the two alleles should not be in Hardy-Weinberg equilibrium. The data thus seems to indicate that the presence of I versus D alleles is selectively neutral. This neutrality could be true either if the two alleles had no effect on fitness (from an evolutionary point of view), or if there were opposing effects from two different selective forces each of which acted to maintain a particular allele in the population. The classic example is the haemoglobin gene, in which HbS allele confers protection against malaria in the heterozygous state, but confers reduced lifespan and fertility in the homozygous state. With these seemingly obvious advantages of the I allele, what selective forces might act to maintain the D allele in the human population? One possibility is limited food availability. Although increased muscle mass (or more precisely, increased anabolic response to physical training) has clear advantages under several circumstances, it also requires a high energy intake to maintain that muscle mass. Faced with the situation of limited food supply there are at least two evolutionary strategies an organism can use. The first is to increase efforts to obtain food. The II genotype would seem to offer some advantages here, and when the going gets tough, the II bulk up and get tougher. An alternative strategy is to reduce muscle mass and thereby decrease the amount of food that needs to be gathered. When the going gets tough, the DD hunker down and hope for better times. Which strategy is better? Since the two alleles are in equilibrium, there must be selective pressures acting to maintain both alleles. Although we tend to think of evolution acting to enhance performance, this is not necessarily true. Evolution perpetuates strategies that work, for whatever reason.