Sickle-Cell Disease and Natural Selection

How could natural selection increase the number of children born with sickle-cell disease in certain regions when these individuals are unlikely to survive and produce offspring?


Normal red blood cells next to a sickle cell

Natural selection is at work on a species if three necessary and sufficient conditions are met: that there is a struggle for existence, and therefore some individuals die before successfully breeding; that there is variation in characteristics that can confer advantages or disadvantages in the struggle to survive and breed; and that these characteristics can be passed onto an individual’s offspring. ‘Fitness’, in an evolutionary sense, describes the ability of an individual to survive and reproduce, and for those offspring to successfully reproduce, relative to other members of the species, in an evolutionarily competitive environment. So how can we explain the apparent paradox that natural selection has, in West Africa, produced so many children with such a serious disease as sickle-cell anaemia, most or all of whom will fail the ‘fitness’ test of being able themselves to survive and reproduce?

 We know that the sickle-cell allele can be inherited, so the third of the necessary and sufficient conditions for natural selection is met. Let’s look at the other two conditions more closely. The first is that there is a struggle for existence: in poor, tropical regions like West Africa malaria is still a major killer. So here – to a greater degree than in rich industrialised countries – an evolutionary struggle for existence still applies. Many individuals here are dying before being able to have children, because of malaria.

Sickle-cell disease is inherited in the autosomal recessive pattern [Cburnett - Own work in Inkscape]
Sickle-cell disease is inherited in the autosomal recessive pattern [Cburnett – Own work in Inkscape]

Secondly, there must be a variation in characteristics that can confer evolutionary advantage and/or disadvantage. This is where the sickle-cell allele demonstrates a striking ‘trade-off’ between benefit and cost. Individuals who carry just one sickle-cell allele have significantly greater resistance to malaria than individuals without any sickle-cell allele – a major advantage where malaria is so lethal, giving them a greater chance to stay healthy long enough to have children. But individuals who happen to inherit two sickle-cell alleles suffer the crippling disadvantage of contracting the disease, and are very unlikely to survive to have children themselves. So this ‘trade-off’ applies, not to an individual, but rather to a genetic population – conferring a major advantage to individuals lucky enough to inherit just one sickle allele, but punishing the individuals unlucky enough to inherit two sickle alleles.

 So which side of this trade-off wins out overall – the advantage to the sickle-cell carriers, or the disadvantage to the sickle-cell disease sufferers? An important factor concerns the probability of offspring genotypes: if two sickle carriers (already the recipients of a malarial advantage over non-carriers) have a child, that child is twice as likely to have a heterozygous carrier genotype as a homozygous disease genotype – so it is statistically twice as likely to inherit a malarial advantage than a sickle disease disadvantage. This 2:1 ratio of overall advantage to disadvantage helps to explain the spread of the sickle allele throughout the malarial regions of Africa.

Modern day malaria distribution

The sickle-cell allele must have appeared as a spontaneous mutation once, or at most in a few independent cases. The fact that an allele that carries such a heavy evolutionary disadvantage as full-blown sickle-cell anaemia has spread to become so prevalent across a huge region, testifies strongly that, in terms of natural selection, to be a sickle carrier confers a fitness benefit relative to non-carriers, and relative to the counter-balancing disadvantage of full sickle disease. This resolves the paradox of this essay’s title – natural selection can indeed increase the numbers of individuals who carry a serious evolutionary burden (sickle anaemia sufferers), if in the population as a whole their disadvantage is outweighed – in this case in a population ratio of 2:1 – by the advantage held by their more fortunate siblings (sickle carriers).

Article for OU Module S104 Exploring Science © Andrew Murray 2012


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