Lethal Genes

Any gene that has an effect on the organism’s death at any stage of life. A gene that has a profoundly unfavourable effect on the phenotypic and causes the organism to exhibit numerous adverse features, which might eventually result in death. A deadly gene is one that results in an organism dying before reproduction is feasible or that prevents reproduction; for recessive genes, the homozygous or hemizygous condition is lethal.

Lucien Cuénot identified lethal alleles in 1905 while examining the inheritance of coat colour in mice. In mice, the agouti gene is mostly responsible for coat colour. The wild-type gene results in a mixture of yellow and black pigmentation in the mouse’s hair. This yellow and black colour combination is known as ‘agouti’. One of the agouti gene’s mutant variants leads to mice that are significantly lighter and yellowish in colour. When these yellow mice were bred with homozygous wild-type mice, they produced offspring with a 1:1 ratio of yellow to dark grey. This demonstrated that the yellow mutation is dominant, as all yellow parental mice were heterozygotes for the mutant allele.

Cuénot expected to witness a typical 1:2:1 Mendelian ratio of homozygous agouti to heterozygous yellow to homozygous yellow after mating two yellow mice. Rather than that, he consistently saw a 1:2 ratio of agoutis to yellow mice. He was unable to generate any homozygous mice for the yellow agouti allele.

1. E. Castle and C. C. Little validated Cuénot’s work in 1910, revealing that one-quarter of offspring died during embryonic development. This was the first instance of a recessive deadly allele being documented.

Types of lethal allele

Recessive lethals

The term recessive lethal alleles refer to a pair of identical alleles that are both present in an organism and ultimately result in the organism’s death. While recessive lethals can code for either dominant or recessive features, they are fatal only in the homozygous state. Heterozygotes may occasionally have a pathological phenotype, such as achondroplasia. While having one mutant deadly allele is tolerable, having two leads in death. When homozygous achondroplasia is present, death nearly often occurs prior to birth or during the perinatal period. Not all heterozygotes for recessive fatal alleles will manifest a mutant phenotype, as is the case with carriers of cystic fibrosis. If two carriers of cystic fibrosis have children, they have a 25% chance of creating offspring with two copies of the fatal allele, which will eventually result in the child’s death.

The Manx cat is another example of a recessive deadly allele. Manx cats are heterozygous for a mutation that results in a shortened or absent tail. Crossing two heterozygous Manx cats produces two-thirds of surviving offspring with the heterozygous shorter tail phenotype and one-third of surviving offspring with the normal tail length who are homozygous for the normal allele. Homozygous mutant progeny is unable to survive birth and are so absent from these crosses.

Dominant lethals

Alleles that are fatal if only one copy is present in an organism are referred to as dominant lethal alleles. These alleles are uncommon in populations because they usually cause an organism’s death before it can pass on its fatal allele to its descendants. Huntington’s disease, a rare neurological condition that eventually results in death, is an example of a dominant deadly allele in humans. However, because it manifests late (i.e., frequently after reproduction has occurred), it is able to persist in populations. Huntington’s disease occurs when a person carries a single copy of the repeat-expanded Huntington gene on chromosome 4.

Conditional lethals

Alleles that are lethal only in certain environmental conditions are referred to as conditional lethals. A conditional deadly condition is favism, a sex-linked genetic disorder that leads the carrier to develop hemolytic anaemia after eating fava beans.

At a high limiting temperature, infection of an E. coli host cell with a bacteriophage (phage) T4 temperature sensitive (ts) conditionally lethal mutant results in the absence of viable phage production. However, such mutants can grow at lower temperatures. These conditionally lethal mutants have been utilised to characterise and identify a large number of the phage’s genes. Thus, genes involved in DNA repair as well as genes involved in genetic recombination were identified using its mutants. For instance, cultivating a ts DNA repair mutant at an intermediate temperature will result in the production of some offspring phage. However, when that mutant is exposed to UV radiation, its survival is significantly reduced in comparison to that of irradiated wild-type phage T4. Additionally, cold sensitive conditional lethal mutants were discovered in phage T4 that were capable of growing at high temperatures but not at low temperatures. Additionally, these temperature-sensitive conditional lethal mutants defined a group of phage genes. Another type of conditional lethal phage T4 mutants known as amber mutants is capable of growing on some strains of E. coli but not on others. Additionally, these mutations were utilized to identify and characterise a large number of phage T4 genes, including those encoding proteins involved in DNA repair, genetic recombination, DNA replication, and molecular morphogenesis. Additionally, it was discovered that an amber mutation generates a “nonsense codon” within a gene, resulting in the end of polypeptide chains during translation. This discovery shed light on a critical part of the genetic code.

Conclusion

Lethals, also known as lethal genes or lethal alleles, are alleles that result in the death of the entity that carries them. Essentially, fatal genes are lethal to the creature that carries them, with lethal referring to (in this case) death. Typically, growth and development are necessary as a result of gene mutation. In 1905, while doing research on the inheritance of coat colour in mice, French geneticist Lucien Cuénot discovered the first Lethal genes. According to Cuenot, yellow was dominant over brown, ruled over by a single gene called “Y.” As a result, he discovered that mice could never be yellow under homozygous circumstances.

Lethal genes can be dominant, recessive, or even conditional in nature, depending on the genes involved. Death can occur at any point throughout an entity’s evolution, but it is most common during the early stages.