Pleiotropy

Definition. The genotypes considered so far have а specific effect on а specific trait. This, however, is not true for all the genes. Probably most genes influence not only the traits generally associated with them but also many other traits. The multiple effect of а gene is called pleiotropy, and а gene having multiple phenotypic effects is called а pleiotropic gene.

Pleiotropic genes may not have equal influence on all the traits they control. А pleiotropic gene may cause а very evident expression of its specific trait (major effect) and а less evident expression of its other traits (secondary effect).

Examples. The genes that control the flower colour in sweet peas also control the colour of the seed coats and red spots in axils of the leaves. Another example of pleiotropy is the human disease called sickle-cell anaemia. The genes which cause this disease alter the type of haemoglobin and also change the form of red corpuscles.

Sickle-Cell Anaemia. Sickle cell anaemia is а hereditary disease found widely in tropical Africa and also in American blacks whose ancestors came from that part of Africa. It is characterized by sickle-shaped red blood corpuscles formed under low oxygen conditions. Change in the shape of red blood corpuscles is due to the presence in them of а defective type of haemoglobin called sickle cell haemoglobin or haemoglobin S. This is the major effect of the pleiotropic gene and formation of sickle-shaped corpuscles by haemoglobin S is one of the secondary effects. The molecule of haemoglobin S has а different shape from that of the normal haemoglobin (called haemoglobin А) molecule. When the red blood cells containing haemoglobin face O₂ shortage, their haemoglobin molecules aggregate and form stiff fibres. These fibres distort the cells into odd shapes such as sickles. Because оf their inflexibility, the sickle-shaped corpuscles cannot easily squeeze through narrow capillaries unlike the normal flexible corpuscles which change their shape 1о pass through narrow capillaries. The sickled cells get stuck in the small capillaries and reduce circulation to the regions supplied by these vessels. The sickled cells also break down easily, decreasing the number of red blood corpuscles leading to anaemia. Poor circulation and anaemia are other secondary effects of the pleiotropic genes. These effects deprive the tissues of oxygen. This also produces а variety of other symptoms such as tiredness, headache, fever, muscle cramps, poor growth, jaundice, low resistance to infection, and possibly failure of heart and kidneys.

The gene involved in sickle cell anaemia codes for the beta polypeptide chain of haemoglobin — the oxygen-carrying protein present in the red blood corpuscles, imparting them their red colour. Sickle cell anaemia develops in the individuals who have а sickle allele formed by а change in just one nucleotide pair in its DNA. This alteration results in the substitution of one amino acid — valine for glutamic acid — which is the sixth amino acid in the beta polypeptide chain of haemoglobin. This small change turns the haemoglobin А into haemoglobin S. The disease is manifested only in homozygous recessive state, i.e., when an individual has both the alleles for sickle- cell haemoglobin (HbS, HbS). The individuals homozygous for sick1e cell anaemia are called affected individuals. About half of the affected individuals die by the age of 20. Moreover, affected women have fewer babies than the heterozygous or homozygous normal women have. Natural selection keeps the lethal sickle allele at а low frequency in the population because many affected persons die without producing offspring. Yet 20 — 40% of people in tropical Africa have the sickle allele in heterozygous condition. This shows that the heterozygotes have some selective advantage. Presence of а single sickle allele lowers the heterozygotes chances of developing malaria. The red blood corpuscle having abnormal haemoglobin sickle more readily when they are infected with malarial parasites. The parasites of sickled cells die. The remaining parasites are then destroyed by the body's defenses before malaria develops. Thus, the sickle allele in heterozygous condition protects the person against malaria.