Question

Price et al. (1999. J. Bacteriol. 181: 2358-2362) conducted a genetic study of the toxin transport protein (PA) of Bacillus anthracis, the bacterium that causes anthrax in humans. Within the 2294-nucleotide gene in 26 strains they identified five point mutations-two missense and three synonyms-among different isolates. Necropsy samples from an anthrax outbreak in 1979 revealed a novel missense mutation and five unique nucleotide changes among ten victims. The authors concluded that these data indicate little or no horizontal transfer between different \(B\). anthracis strains. (a) Which types of nucleotide changes (missense or synonyms) cause amino acid changes? (b) What is meant by horizontal transfer? (c) On what basis did the authors conclude that evidence of horizontal transfer is absent from their data?

Short answer

Answer: Missense mutations cause amino acid changes in proteins, whereas synonyms do not. The difference between these two types of mutations is that a missense mutation is a change in a single nucleotide that results in a different amino acid being incorporated into a protein, altering its function, while a synonym mutation is a change in a single nucleotide that does not affect the amino acid produced due to the flexibility of the genetic code allowing some amino acids to be encoded by more than one codon.

Step-by-step solution

(a) Types of Nucleotide Changes

(A nucleotide change can be either missense or synonym. A missense mutation is a change in a single nucleotide that results in a different amino acid being incorporated into a protein, thereby altering its function. In contrast, a synonym mutation is a change in a single nucleotide that does not affect the amino acid produced, because some amino acids can be encoded by more than one codon. Therefore, missense mutations cause amino acid changes, while synonyms do not.)

(b) Horizontal Transfer Definition

(Horizontal transfer, also known as lateral transfer, refers to the transfer of genetic material between organisms in a method that is not directly inherited from a parent or ancestor. This can occur through mechanisms such as conjugation, transformation, or transduction. It results in the acquisition of new traits or genes in an organism, which can lead to increased genetic variety and the possibility for adaptation in populations.)

(c) Absence of Evidence for Horizontal Transfer

(The authors concluded that there was little or no evidence of horizontal transfer in their data based on the low amount of genetic variation observed among the different strains of Bacillus anthracis. They identified only five point mutations (two missense and three synonyms) in the 2294-nucleotide gene across 26 strains, and a novel missense mutation along with five unique nucleotide changes among ten victims of an anthrax outbreak. This low level of genetic diversity suggests that the strains are not frequently exchanging genetic material through horizontal transfer mechanisms, as higher genetic diversity would be expected if horizontal transfer were common.)

Key concepts

Missense Mutation

A missense mutation is a type of point mutation where a single nucleotide change in the DNA sequence results in the substitution of one amino acid for another in the resulting protein. This occurs because genetic code sequences of amino acids are determined by codons, which are combinations of three nucleotides. When even one nucleotide in a codon is altered, it can change the corresponding amino acid in the protein chain. This change can significantly alter the protein's structure and function.
For example, if the original codon was GAG, which codes for the amino acid glutamine, and a mutation changes the last nucleotide to GAA, the new codon now codes for the amino acid glutamic acid instead. This type of mutation can have various effects:

• In some instances, it may alter the protein's function, potentially leading to diseases or conditions.
• In other cases, the mutation might not significantly affect the organism if the protein's function remains relatively stable despite the amino acid change.

Overall, the impact of a missense mutation on an organism largely depends on where in the protein the change occurs and how critical that particular amino acid is to the protein's overall role.

Synonymous Mutation

A synonymous mutation, also known as a silent mutation, is a change in the DNA sequence that does not alter the amino acid sequence of the protein. This occurs because multiple codons can code for the same amino acid, thanks to the redundancy of the genetic code.
For instance, the codons GGU, GGC, GGA, and GGG all code for the amino acid glycine. If a mutation changes GGU to GGA, the resulting amino acid would still be glycine. Thus, despite the change in the DNA sequence, the protein remains unchanged in its amino acid composition.
Synonymous mutations are typically seen as neutral with respect to protein function, but they can still have subtle effects:

• They could influence the efficiency of protein synthesis by affecting translation speeds.
• They might have impacts on the folding of mRNA, potentially altering how proteins are formed.

Even though these mutations do not alter the protein's primary structure, their effects on cellular processes can sometimes be significant and are an important consideration in genetic studies.

Horizontal Gene Transfer

Horizontal gene transfer (HGT), or lateral gene transfer, is a process by which organisms exchange genetic material with each other in a manner that does not involve direct inheritance from parent to offspring. This process is particularly common among bacteria and can occur through several mechanisms:

• Conjugation: This involves the direct transfer of DNA from one bacterium to another through direct contact.
• Transformation: Involves the uptake of free DNA fragments from the environment by a bacterial cell.
• Transduction: Occurs when a virus transfers genetic material between bacteria.

The significance of horizontal gene transfer lies in its ability to speed up genetic variation and evolution. It allows organisms to quickly acquire new traits, such as antibiotic resistance, enhancing their adaptability and survival in changing environments.
The absence of significant horizontal gene transfer can indicate a slow adaptation rate among populations, as seen in the genetic study of Bacillus anthracis. Limited genetic variation, as noted in the study, suggests that these bacteria strains did not commonly exchange genetic information through HGT, hence maintaining a stable genetic composition over time.