The principles of Mendelian genetics led to the conclusion that the gene mutations affect the phenotypic expression in an individual. The mutation either leads to the manifestation of a phenotype undesirable to the human being or variations causing the evolutionary changes. Certain studies, later on, revealed the lethality of the mutant alleles and the alleles causing the death of an individual when present in a certain dosage.
A lethal allele easily causes the death of an organism. The essential genes cause a lethal phenotype on getting mutated. There are two types of lethal alleles such as dominant lethal allele and recessive lethal allele. Both the homozygotes and the heterozygotes exhibit a lethal phenotype due to the dominant lethal allele. In the case of the recessive lethal allele, only the homozygotes exhibit the phenotype.
An example of the recessive lethal allele involves the yellow body color of mice. Breeding of all yellow mice resulted in a phenotypic ratio of 3:1 (yellow: nonyellow). On repetition of the cross between yellow mice, the phenotypic ratio changed to 2:1 ratio. The yellow allele expressed itself as a dominant allele for the coat color. The same allele also acts as a recessive allele in case of lethality phenotype since only the homozygotes die at the embryo stage. The agouti locus consists of the yellow allele. In the homozygous state, the recessive allele causes lethality. The agouti yellow gets expressed in all the tissues in the developmental stages. The heterozygous lethal allele arises due to the deletion of a large segment between the agouti locus and a gene known as a raly gene. As a result of the deletion mutation, the raly promoter gene gets fused with the agouti gene. Due to this mutation, the raly promoter now controls the expression of the agouti gene. Mainly the regulatory signals present in the promoter region of the Raly control the expression of agouti yellow in all the tissues. Thus the lethality of yellow homozygotes results from the absence of raly gene activity.
Image: Effect of lethal alleles
Types of lethal alleles:
· Recessive lethal alleles:
They result in the death of an organism. The recessive lethal alleles involve an identical pair of alleles exhibiting recessiveness. Most of them occur in the homozygous state. Hence, they are fatal. These alleles not only code for the recessive traits but also code for the dominant traits. Diseased phenotype sometimes gets expressed in the heterozygote individuals. An example includes heterozygote individuals in Achondroplasia, a disorder related to dwarfism. If one lethal allele occurs, the individual still tolerates it. Hence, the heterozygotes having one lethal allele still manage to survive. However, if the lethal allele occurs in a double dose, it becomes lethal. The condition is known as a homozygous condition. Lethality gets often associated with the death of the individual or the organism. In homozygous Achondroplasia individuals, death occurs before birth or in the perinatal stage. Consider another example of recessive lethal alleles in cystic fibrosis. It is an autosomal recessive disorder affecting 1in 2500 people. The mutations in the CFTR gene reduce the intracellular sodium chloride levels. The CFTR gene mutation thereby induces the secretion of thick mucus. The cystic fibrosis carriers do not show the mutant phenotype even though they have one recessive lethal allele. However, if the two heterozygote carriers marry and plan to have children, 25% of them experience lethality. Hence, such individuals die due to the presence of two recessive lethal alleles obtained from each of the carrier parents.
Dominant lethal alleles:
These alleles manifest the phenotype even when they occur in a single copy. In short, one dominant lethal allele is enough for the expression of the trait. Such type of lethal alleles causes the death of an organism. If these individuals survive till their age of reproduction, the dominant lethal alleles persist in the population. Otherwise, they become rare. The dominant lethal alleles involve a classic example of Huntington's disease. It affects the movements of an individual and occurs as an autosomal dominant disorder. The mutated gene consists of an abnormally large CAG nucleotide repeat. The disease leads to the premature death of the individual. Those carrying a single copy of the dominant lethal gene reproduce, they easily pass on the gene to the next generation. Hence we say that the dominant lethal alleles kill the heterozygotes as well as the homozygotes.
Conditionally lethal genes:
These lethal alleles exhibit their lethality only under certain environmental conditions. Hence, they are known as conditionally lethal alleles. An example of conditionally lethal genes involves a condition known as favism. It is a hereditary disorder involving fava bean allergy. These individuals suffer from the hemolytic anemia upon the consumption of the beans. It involves a sex-linked inheritance. It occurs due to the deficiency of the glucose-6-phosphate dehydrogenase enzyme. The defective allele encoding this enzyme causes lethality or death only under certain conditions. Hence, it is a conditionally lethal allele.
Essential genes:
Essential genes help the organism for completing the developmental processes and survival. Essential genes also play a role in human disease. Mutations in these genes involve lethality. Hence, their functions get altered based on the type of the mutation. Hence, they contribute to human disease. These genes also participate in protein-protein interactions. Consider an example of essential genes. The leaf color in a snapdragon plant is an important example of essential genes. This plant has a leaf color ratio of 2 yellowish: 1 green. The homozygous yellowish embryos die due to the presence of lethal genes. A disease in humans involves a CNS impairment called as Tay-Sachs disease. The HEXA gene encodes an important enzyme known as hexosaminidase A. These individuals suffer from the deterioration of the central nervous system, mental retardation, and vision impairment.
Certain genes known as conditionally essential genes do not work all the time. Hence, they are conditionally essential. Suppose a cell receives an adequate supply of lactose sugar. The genes encoding the lactose sugar remain inactive. They get activated only when there is a deficiency of lactose in the cells. Hence, these genes are known as conditionally essential genes.
References:
[1] Biology: A Functional Approach, M. B. V. Roberts
[2] Genetics, 9th Edition (Multicolour Edition), Verma P.S. & Agarwal V.K.
[3] IGenetics, Peter Russell, second edition
References:
[1] Biology: A Functional Approach, M. B. V. Roberts
[2] Genetics, 9th Edition (Multicolour Edition), Verma P.S. & Agarwal V.K.
[3] IGenetics, Peter Russell, second edition
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