Question

Price et al. I(1999). J. Bacteriol. 181:2358-2362] conducted a genetic study of the toxin transport protein (PA) of Bacillus anthra. cis, the bacterium that causes anthrax in humans. Within the 2294-nucleotide gene in 26 strains they identified flve 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 hori- zontal transfer is absent from their data?

Short answer

Answer: The types of nucleotide changes that cause amino acid changes are called missense mutations. In the genetic study of the toxin transport protein (PA) of Bacillus anthracis, the authors observed a low number of missense mutations, leading them to conclude that there has been little or no horizontal transfer between different Bacillus anthracis strains.

Step-by-step solution

(a) Types of nucleotide changes causing amino acid changes

The nucleotide changes that cause amino acid changes are called missense mutations. They occur when a single nucleotide in the DNA sequence is altered, leading to a different amino acid being incorporated into the protein during translation. In contrast, synonymous mutations do not change the amino acid sequence, since the genetic code is degenerate or redundant for many amino acids, meaning that multiple codons can encode for the same amino acid.

(b) Definition of horizontal transfer

Horizontal transfer, also known as lateral gene transfer, is a process through which genetic material is transferred between different individuals of the same or different species. This is different from vertical transmission, where genetic material is passed down from parent to offspring through sexual or asexual reproduction. Horizontal transfer can occur through various mechanisms, such as transformation (uptake of free DNA), transduction (viral-mediated transfer), or conjugation (direct cell-to-cell contact).

(c) Authors' conclusion on the absence of horizontal transfer

The authors based their conclusion on the low number and types of mutations found among the analyzed Bacillus anthracis strains. They observed that there were only five point mutations (two missense and three synonymous) among the 26 strains and a total of six unique nucleotide changes in the 1979 outbreak analysis. The lack of genetic diversity, especially in the types of mutations (which mostly had no impact on the protein sequence), indicates that there has been little or no horizontal transfer between different Bacillus anthracis strains. If horizontal transfer were occurring frequently, one would expect to see greater genetic diversity and possibly more consequential mutations in the nucleotide sequence.

Key concepts

Missense Mutations

When studying the genetic makeup of Bacillus anthracis, scientists pay particular attention to changes in the DNA sequence that may affect the organism's characteristics. One type of such change is the missense mutation. This occurs when a single nucleotide change leads to the substitution of one amino acid for another in the resulting protein. For instance, if the codon that originally coded for the amino acid lysine changes to one that codes for asparagine, the protein's structure and function could be significantly altered.

Such modifications can impact the virulence or survivability of the bacteria. In the case of Bacillus anthracis, the authors of the study identified two missense mutations which suggest that these changes could potentially affect the toxin transport protein's function. These mutations are particularly noteworthy because they produce a tangible change in the organism which could lead to differences in disease manifestation or response to treatment.

Real-World Implications of Missense Mutations

In practical situations, missense mutations can lead to various outcomes. They can render a protein nonfunctional, potentially causing disease, or, in some cases, they may confer an evolutionary advantage, such as antibiotic resistance. Identifying these mutations helps researchers understand the genetic factors that may influence the severity or transmission of anthrax.

Synonymous Mutations

Synonymous mutations, also known as silent mutations, are a different type of nucleotide change that do not result in an altered amino acid sequence. This is because the genetic code is redundant; multiple three-nucleotide codons can specify the same amino acid. In the study of Bacillus anthracis, the researchers found three synonymous mutations within the toxin transport protein gene.

While these mutations do not change the protein's primary structure, they may still play a role in how efficiently the protein is produced. Factors like codon usage bias can affect translation speed and accuracy, potentially influencing bacterial growth and virulence. Synonymous mutations are crucial for understanding the subtle ways in which DNA variations can impact biological processes without altering protein sequences.

Impact on Genetic Studies

By studying synonymous mutations, scientists gain insight into evolutionary pressures and genetic drift. These mutations can serve as molecular clocks, providing clues about the timing of species divergence or the spread of certain traits without displaying immediate phenotypic effects.

Horizontal Gene Transfer

Unlike mutation, which is an alteration of the genetic material within a single organism, horizontal gene transfer is the movement of genetic information between different organisms or species. This process can be natural, like when bacteria acquire resistance genes from their environment, or it may be facilitated by human intervention, such as in genetic engineering.

In the context of Bacillus anthracis, horizontal gene transfer would mean that genetic material could pass between individual bacteria, potentially sharing advantageous traits like toxin production or antibiotic resistance. The absence of evidence for horizontal gene transfer in the Price et al. study suggests that the genetic differences observed were most likely due to mutations occurring over time within isolated strains rather than the exchange of genes with others.

Consequences and Concerns

Understanding horizontal gene transfer is vital, especially in pathogenic bacteria, since it contributes to the rapid spread of antibiotic resistance and the emergence of new virulent strains. It poses challenges in treating infectious diseases and necessitates continuous monitoring of bacterial genetic changes to prevent outbreaks.

Genetic Diversity

Genetic diversity is the cornerstone of survival and evolution for all organisms, including bacteria like Bacillus anthracis. It refers to the total number of genetic characteristics in the genetic makeup of a species. High genetic diversity allows populations to adapt to changing environments and resist threats such as diseases or environmental changes.

The limited genetic diversity observed in the Bacillus anthracis study may suggest a reduced capacity for adaptation or could indicate a relatively recent common ancestor for the strains examined. This finding is significant when considering the evolutionary history of the bacteria and in developing strategies for managing anthrax outbreaks. The study of genetic diversity also has broader implications in conservation biology, agriculture, and medicine, offering insights into species’ health and their ability to adapt to changing conditions.

The Importance for Pathogenic Bacteria

In pathogenic bacteria, low genetic diversity can imply a uniform susceptibility to antibiotics, making it easier to control an outbreak. On the other hand, high genetic diversity might lead to the emergence of resistant strains, necessitating more complex and varied treatment approaches. Deciphering the genetic diversity within pathogen populations helps in predicting the course of diseases and in tailoring public health responses accordingly.