The Genetics Behind the Survival of Sickle-Cell Disease
Alternative versions of a gene are alleles. Each gene resides at a specific chromosome locus. The DNA at that locus, however, can vary somewhat in sequence of nucleotides and information content. Alleles are these possible DNA variations.
Individuals who are homozygous for an allele have both alleles of the same sort, one on each pertinent locus of two homologous chromosomes. Individuals who are heterozygous for an allele have two different alleles, one on each of the homologous chromosomes.
Natural selection through differential reproductive success can cause allele frequencies in a population to change. Disasters or dramatic changes in the environment can also bring about a bottleneck effect whereby the small quantity of individuals remaining does not statistically represent the former population. Thus, the available gene pool has been altered dramatically.
Malaria is a tropical disease transmitted through the bite of a mosquito. The malarial protozoa infect the liver and reproduce, subsequently infecting the victim’s red blood cells and becoming available for transfer to other individuals via another mosquito.
People in Africa or of African descent often carry the sickle-cell anemia allele because heterozygotes for the allele can be protected from malaria while not exhibiting considerable symptoms of sickle-cell anemia. They can survive to reproductive age and transfer the allele to offspring, thus perpetuating the allele’s occurrence in the gene pool.
Natural selection can serve as a mechanism for the survival in heterozygotes of certain recessive alleles which pose great harm to recessive homozygotes. If the allele confers an advantage to a heterozygote that is lacked by the dominant homozygote (which in this case is vulnerable to malaria), this allele can be spread to future generations, since its carriers reach reproductive age with greater likelihood. In a different environment, however, where malaria does not occur frequently or at all, there will be little or no survival advantage from being a carrier of the sickle-cell allele. Although these individuals can still reproduce without great obstacles, they are no longer favored over the homozygous dominant genotype. Thus, in places such as the United States, the sickle-cell allele is not nearly as frequent as in the tropical regions of Africa. Nevertheless, it does occur in a very small percentage of the population of African descent, seeing as insufficient time has passed in order for the allele frequency to decline to negligible amounts.
One of the reasons why sickle-cell disease can still potentially exist in malaria-free environments is the fact that heterozygotes’ normal phenotypes “mask” the existence of the allele within their genotypes. Thus, they can mate with healthy heterozygote partners and produce diseased offspring. Perhaps technological advancement in the near future will enable individuals to learn of their own genotypes and the possibility of transferring such diseases to their children, thus enabling them to make more prudent decisions concerning reproduction. Heterozygotes may choose to marry dominant homozygotes in the United States, or clone themselves in Africa so as to ensure that malaria resistance will be passed to their children without the risk of them acquiring sickle-cell disease.
Yet natural selection does not always function in a perfect or desirable manner. In many experimental cases, introducing just one heterozygote into an area with high rates of malaria death failed to establish the sickle-cell allele. Many factors can account for this, including the possibility that the heterozygote did not transfer the recessive allele to his offspring, or that he died of a cause absolutely unrelated to malaria or sickle-cell anemia prior to transferring the allele to offspring.