Molecular and Genomic Epidemiology of Infections

Question 1

What types of mutations are there?

Answer 1

Silent : Mutations that are Intragenic (between genes)
or Synonymous (not altering coding)

Non-Synonymous: Substitutions causing coding to be altered

Corruptive: Deletions or Insertions (disrupting coding frame)
` Creation of STOP codons (truncation)
Corruption of STOP codons (elongation)
Corruption of CONTROL sequences (eg. promoters)

Question 2

What is drift? What is antigenic drift?

Answer 2

Gradual alteration in sequence is called DRIFT.

Some mutations have more influence on Ab
binding affinity than others
Herd immunity (after large vaccination program)
kills most but also selects for escape mutants that
maintain the drift

Antigenic drift is the same antigen changing its sequence base by base

Antigenic shift is a sudden replacement of an antigen by recombination with another viral type that has evolved separately (either in another animal or another
human population). New types will not be protected against by previous infection or vaccination - leading to new epidemics

Question 3

What factors can affect the speed of the ‘molecular clock’ in regards to mutation rate?

Answer 3

Bacterial replication rate:
A high division rate provides a higher mutation rate

DNA or RNA polymerase proof reading fidelity:
Some species (eg HIV) have low fidelity promoting high mutation rate

Selection pressure from the host or environment:
High selection pressure removes ‘weak’ mutants and emphasises clusters
Loss of selection pressure allows deletions

Degree of redundancy in the genome:
multiple copies of a single gene in the genome allow for
mutations in one copy without compromising overall functionality
Movement or recombination within genome may not effect phenotype

Transmission rate:
High transmission rates relative to the mutation rate
results in dissemination and single strain outbreaks
(Flu A = 2-3 bases per year and 1.5 transmissions per infection)

Question 4

Which genes change the most in mutations?

Answer 4

Hyper-variable genes change more rapidly than conserved genes
but
Conserved genes are more likely to be associated with phenotype and virulence
—————–
Not all changes are new
Some may revert BACK to an older profile (convergent evolution)
—————-
Large and rapid changes are rare
but often lead to escape from existing herd protection

Some genes could be replaced completely!
(Antigenic SHIFT)