Natural selection works by weeding less fit variants out of a population. We would expect natural selection to remove alleles with negative effects from a population, and yet many populations include individuals carrying such alleles. Human populations, for example, generally carry some disease-causing alleles that affect reproduction. So why are these deleterious alleles still around anyway? What keeps natural selection from getting rid of them? There are several possible explanations:
They may be maintained by heterozygote advantage
When carrying two copies of an allele is disadvantageous, but carrying only one copy is advantageous, natural selection will not remove the allele from the population — the advantage conferred in its heterozygous state keeps the allele around. For example, the allele that causes sickle cell anemia is deleterious if you carry two copies of it. But if you only carry one copy of it and live in a place where malaria is common, the allele is advantageous because it confers resistance to malaria.
- They may be maintained by mutation
The mutation producing the deleterious allele may keep arising in the population, even as selection weeds it out. For example, neurofibromatosis is a genetic disease causing tumors of the nervous system. Natural selection cannot completely eliminate the gene that causes this disease because new mutations arise relatively frequently — in perhaps 1 in 4000 gametes.
- They may be maintained by gene flow
The allele may be common, and not deleterious, in a nearby habitat. If gene flow from the nearby population is common, we may observe the deleterious allele in the population of interest. For example, in places like the U.S., where malaria is not a problem, the gene that causes sickle cell anemia is strictly disadvantageous. However, in many parts of the world, the gene that causes sickle cell anemia is more common because a single copy of it confers resistance to malaria. Human migration causes this gene to be found in populations all over the world.
- Natural selection may not have had time to remove them yet
The direction of selection changes as the environment changes; what was advantageous or neutral ten generations ago may be deleterious today. It is possible that some of the deleterious alleles that we observe in natural populations are on their way out, but selection has not yet completely removed them. For example, although there is debate about the issue, some researchers have proposed that the relatively high frequency in European populations of the allele causing cystic fibrosis is a historical holdover from a time when cholera was more rampant in these populations. It is proposed that carrying the cystic fibrosis allele provided some resistance to cholera and so increased in frequency in earlier European populations. Now that these developed nations are no longer threatened by cholera and the selective environment has changed, natural selection may be slowly weeding the cystic fibrosis allele out of those populations.
- They may not really reduce fitness
Some genetic disorders only exert their effects late in life, after reproduction has taken place. For example, the allele that causes Huntington’s disease typically does not exert its devastating effects until after a person’s prime reproductive years. So although Huntington’s disease is certainly deleterious in terms of quality of life, it is not deleterious in terms of reproductive ability and is not selected against.
Learn more about sickle cell anemia or Huntington's disease.