THE HISTORY OF SICKLE- CELL ANEMIA AND MALARIA
THE HISTORY OF SICKLE- CELL ANEMIA AND MALARIA In the late 1950s, the American physical anthropologist Frank B. Livingstone (1928–2005) sought to strengthen the case for natural selection by historically linking sickle- cell anemia and malaria. Livingstone asked two important questions: Where and when did the sickle- cell allele first appear in equatorial Africa? and What conditions led to the allele’s being naturally selected? He hypothesized that the Bantu, a group of peoples who speak Bantu languages, carried the mutation with them when they migrated south- ward from the region of Cameroon and Nigeria (Figure 4.17). Prior to the Bantu’s arrival, the region was a largely unbroken forest. Bantu populations introduced agri- culture there, clearing large swaths of the forest for cultivation. The peoples’ iron- working technology made possible the creation of tools for cutting down large trees, clearing and plowing fields, and planting crops— mostly yams and cassava.
Even under the best conditions, tropical forests are fragile ecosystems. Once their trees have been cleared and their fields have been planted, their relatively poor soil, which normally soaks up rainwater, becomes thin or disappears. Geo- logical evidence shows a dramatic increase in soil erosion in the region after the arrival of Bantu populations, due in large part to anthropogenic deforestation and the overall environmental impact of humans on the landscape. As a result of these erosive processes, pools of water collect and become stagnant, providing ideal conditions for the breeding of parasite- carrying mosquitoes (Figure 4.18). This picture became clear to Livingstone as he developed his research: the newly created ecological circumstances fostered mosquito reproduction and the spread of malaria, and the growing host of humans made possible by agriculture- fueled population growth provided the food resources needed by the mosquitoes. The
(b)(a)
Greater than 14% 12–14% 10–11.9% 8–9.9% 6–7.9% 4–5.9% 2–3.9% 0–1.9%
Areas where malaria is present
FIGURE 4.15 Distributions of the Sickle- Cell Allele and Malaria In equatorial Africa, (a) the distribution of the sickle- cell allele coincides with (b) areas of high malarial parasite concentration.
balanced polymorphism Situation in which selection maintains two or more phenotypes for a specific gene in a population.
anthropogenic Refers to any effect caused by humans.
88 | CHAPTER 4 Genes and Their Evolution: Population Genetics
infectious disease gave those individuals with a very rare mutation— the sickle- cell allele— an adaptive advantage and the ability to survive and reproduce in these new environmental circumstances. Due to the advantage the heterozygous condition provides, the S allele was maintained and passed from generation to generation. For this reason, sickle- cell anemia predominantly affects those whose descendants came from the malarial environments in large parts of equatorial Africa. Outside of such malarial environments, the S allele never became advantageous.
OTHER HEMOGLOBIN AND ENZYME ABNORMALITIES Sickle- cell anemia turns out to be just one of a number of hemoglobinopathies and other genetic abnormalities in Africa, Asia, and Europe that provide a strong selective advantage in regions of endemic malaria (Figure 4.19). Heterozygous carriers of abnormal hemoglobins apparently make poor hosts for malarial parasites.
Thalassemia, a genetic anemia found in Europe (especially in Italy and Greece), Asia, and the Pacific, reduces or eliminates hemoglobin synthesis. In some homozygous forms of the mutation, hemoglobin becomes clumped inside the red blood cells. The spleen then destroys the red blood cells, resulting in severe anemia. In the areas around the Mediterranean where the genetic frequency is highest— as high as 80%—the presence of malaria makes a strong case for a selective advantage for heterozygous individuals, for whom the condition and malaria are not lethal.
An association has long been recognized between deficiency of the enzyme glucose- 6-phosphate dehydrogenase (G6PD) and malaria. A recessive hered- itary mutation leads more males than females to lack the gene that is coded to produce this enzyme (see Figure 4.11). Without the G6PD enzyme, a person who takes sulfa- based antibiotics or eats fava beans risks the destruction of red blood cells, severe anemia, and occasionally death. Because of the connection with fava beans, this severe hemolytic disease is called favism. Its 130 genetic variants occur in high frequencies in some populations, the highest being 70% among Kurdish Jews. Heterozygous carriers have a strong selective advantage because they pro- duce some of the enzyme but are protected from malaria (here again, the parasite cannot live in the abnormal red blood cells).
Analysis of genetic data by the anthropologist Sara Tishkoff indicates that the mutation for the disease arose between about 4,000 and 12,000 yBP, at the same time as the abnormal hemoglobins. Populations whose descendants did not encounter malaria do not have the G6pd mutation or abnormal hemoglobins.
Once inside the human, the sporozoites travel through the bloodstream to the liver. In the liver, the sporozoites create thousands of merozoites. A merozoite is a daughter cell that results from asexual reproduction.
The newly produced merozoites enter the bloodstream and infect the red blood cells. Within these cells, the merozoites continue to multiply, eventually causing the cells to rupture. The merozoites then invade other red blood cells in the bloodstream, and the cycle continues.
a Sporozoite: The goal of sporozoite vaccines is to block parasites from entering or growing within human liver cells.
b Merozoite: Vaccines based on merozoite antigens lessen malaria’s severity by hobbling the invasion of new generations of red blood cells or by reducing complications.
c Gametocyte: So-called altruistic gametocyte- based vaccines do not affect human disease but are designed to evoke human antibodies that derail parasite development within the mosquito.
Over time, some of the merozoites develop into male and female gametocytes, which may be transferred to another mosquito that bites the human host. Gametocytes are cells that can divide to produce gametes, or sex cells.
Within the mosquito, sexual reproduction occurs, as the male gamete fertilizes the female gamete. Oocysts, or zygotes, develop and even- tually release sporozoites. These newly formed sporozoites travel to the salivary glands of the mosquito, where they can be transmitted to the next human the mosquito bites.
Within the mosquito, sexual reproduction occurs, as the male gamete fertilizes the female gamete. Oocysts, or zygotes, develop and even- tually release sporozoites. These newly formed sporozoites travel to the salivary glands of the mosquito, where they can be transmitted to the next human the mosquito bites.
Merozoites
Host’s liver
Host’s red blood cell
INSIDE HUMAN
VACCINE TARGETS
INSIDE MOSQUITO
Female gametocyte
Female gamete
Male gamete
Oocyst
Male gametocyte
Fertilizationc
Sporozoites
A mosquito bites a human, passing sporozoites to the new host. A sporozoite is a motile form of the parasite.
a
b
1
5 2
4
3
FIGURE 4.16 The Spread of Malaria The life cycle of the malarial parasite, Plasmodium falciparum, takes place in two hosts: mosquito and human. Both hosts are needed if the parasite is to survive.
Natural Selection: Advantageous Characteristics, Survival, and Reproduction | 89
infectious disease gave those individuals with a very rare mutation— the sickle- cell allele— an adaptive advantage and the ability to survive and reproduce in these new environmental circumstances. Due to the advantage the heterozygous condition provides, the S allele was maintained and passed from generation to generation. For this reason, sickle- cell anemia predominantly affects those whose descendants came from the malarial environments in large parts of equatorial Africa. Outside of such malarial environments,
