Re: how can harmful recessive alleles be maintained in a population?

Hi Kristie,

I think the answer to this question depends somewhat on what you mean by 'harmful'. In talking about genetics and disease, is important to distinguish between the genotype, which is the set of genes that an organism has, and the phenotype, which is basically what an organism looks like as a result of its genotype. As you probably know, a person with one copy of a recessive allele and a person with no copies of that same recessive allele can have the same phenotype. Only the person with two copies of the recessive allele will have the 'harmful' phenotype. In this example, there are three different genotypes, but only two possible phenotypes. The people with two copies of the same allele (two copies of a recessive allele, or two copies of a dominant allele) are known as homozygotes, while people with one copy of each allele are known as heterozygotes.

So, right here, you can see the beginning of an answer to your question. If only homozygotes for a recessive allele display a harmful phenotype, then heterozygous people can pass that allele on to their offspring, and that allele will remain in the population. However, this answer is actually even more complex than that; the harmful phenotype has to affect your ability to have offspring in order for there to be any effect on the frequency of the recessive allele in the population. In the most extreme example, recessive homozgotes die before they reach puberty. This means that only heterozygotes will be able to pass the recessive allele to the next generation. But if recessive homozygotes survive long enough to reproduce, then their recessive alleles will be passed to the next generation too.

In addition, there are some cases where each genotype (homozygous for the recessive allele, heterozygous, and homozygous for the dominant allele) has a distinct phenotype, and where the heterozygotes have an advantage over either homozygote (this is known as heterozygote advantage). Some examples of this include, Sickle-cell Anemia and Malaria, and probably also Cystic Fibrosis and Cholera.

In these cases, being heterozygous protects you from a pathogen, so the 'harmful' effect of being homozygous for a recessive allele is counterbalanced by the benefits of being heterozygous. This is thought to be the reason why the alleles that result in Sickle-cell anemia and CF are at such high frequencies in specific regions of the world (e.g., Africa and Europe). But you can see here that this effect will be restricted to regions of the world with a particular pathogen.

Finally, remember that heterozygotes for a given recessive allele can have the same phenotype as homozygotes for the 'dominant' allele. Most 'recessive' alleles are non-functional versions of functional alleles that arose via mutations. Such a mutations won't necessarily result in a new phenotype in the first person to inherit it, which means that these sort of recessive alleles are continually being generated at a low rate. In fact, most of us have somewhere around 5-10 non-functional 'recessive' alleles in our genomes (which contain 20,000-30,000 genes). Most of these alleles are very rare, so the chances of us having children with someone who has a recessive allele in the same gene is very low, and therefore the chance of being homozygous for them is very low.

So, to summarize, I suggested four reasons why 'harmful' recessive alleles can be maintained in a population. (1) Heterozygotes for those alleles probably won't have a phenotype, so that the alleles can be passed from heterozygotes to the next generation. (2) The ability of homozygotes for recessive alleles to reproduce (aka their fitness) may not be reduced by their phenotype (even if it is 'harmful'), so that the alleles can be passed by homozygotes to the next generation. (3) Natural selection, in the form of heterozygote advantage, can favor heterozygotes (for example by conferring resistance to a pathogen), resulting in an increase in the frequency of the recessive allele. (4) Mutation continually generates new recessive alleles at a very low frequency, so that there will always be some 'harmful' recessive alleles in a population.

Thanks for asking an interesting question!