Mutations: from viruses to humans

influenza virus particles

 

 

 In this entry, I’ll go over some basic concepts about mutations that might be surprising to most lay persons.  I’ll use viruses, bacteria, and animals as examples.

 

Mutations happen all the time and they could be either for the good or bad of the organism.  Mutations don’t happen directionally, in response to a challenge.  They just appear and then the individual that possesses them either prospers or fails (or is unaffected).  An early experiment illustrates this.  Luria and Delbruck, founders of molecular biology, started with a single clone of E. coli bacteria.  From this, they passaged the bacteria from broth to broth.  They then introduced a selective factor – a deadly bacterial virus (phage).  After this “challenge” they transferred the bacterial cultures (they had done many replicate cultures) to plates to see how many survivors appeared.  The results were quite varied:  some cultures had many survivors and some very few.  Thus, the mutation which allowed resistance to the virus must have arisen early and propagated for some cultures and arose late and was poorly represented for other cultures.  This showed that mutations arise randomly in a population and, when selection comes, those with the appropriate mutation are the “lucky” ones and predominate.

 

Mutation rates are very different between viruses and multicellular organisms like humans.  Humans try to conserve their genomic integrity, so they have elaborate “proofreading” and “mismatch repair” mechanisms to ensure the fewest number of mutations possible (roughly one mutation in the replication of the entire genome (3 billion bases)).  By contrast, HIV makes about one mistake per 1,000 bases.  Most other viruses make less than this, but it is still very high.  It is to the virus’s advantage to make errors, in order to speed its evolution.  The virus is trying to change as fast as it can to keep pace or move beyond the changes in the host’s defense.  Every time new antibodies and T-cells are produced, the virus needs to mutate so that it is no longer recognized by these.  But if it mutates too quickly, it runs the risk of scrambling its own genome! 

 

We keep our genome divided into chromosomes and have developed an elaborate method for shuffling our genes within the population:  sex.  We create haploid versions of ourselves (gametes) and combine these with the gametes of another individual.  In the process of creating the gametes, we shuffle the pieces of each chromosome among each homologous pair.  A homologous pair for, for example, chromosome 4, would be the chromosome 4 you got from your mother and the chromosome 4 you got from your father.  These are shuffled to create a new chromosome 4 you give to your child.  So your genetic system is totally into diversity.

 

 

Some viruses divide their already tiny genome into gene-sized units.  These also can be shuffled if two virus strains happen to infect a single cell.  For influenza virus, avian flu strains and human strains can both multiply in pigs.  Then, humans can become infected with shuffled strains from the pigs.  Birds are clearly the reservoir for the greatest diversity of flu strains, and, lately, some strains have been ported straight over from birds to humans.  The greatest single year epidemic occurred in 1918 when 30 million people died from influenza.  This is why there is such nervousness concerning avian flu.   

 

So mutations are critical for evolution up and down the hierarchy of life.  It is a well-documented phenomenon.

 

[Image from from Linda Stannard, of the Department of Medical Microbiology, University of Cape Town]