Re: On average,how many mutations take place every minute?

Good question, Yan.  The answer depends on several factors, so I will 
explain as I go.

A mutation is a change in the genetic material of a cell, known as DNA.  If 
this change occurs in a germ line cell (egg or sperm or one of the 
precursors to these cells) it is known as a germ line mutation, and can be 
transmitted to the next generation.  On the other hand, if it occurs in any 
other cell in the body, it will only affect the cells descended from that 
cell, and is known as a somatic mutation because it will not be transmitted 
to the next generation.  

There are many types of mutation which can occur in the 3 billion base 
pairs which make up the human genome.  The largest changes which can occur 
are chromosomal translocations and deletions affecting millions of base 
pairs, but these are fortunately very rare.  The most frequent type of 
mutation is a single nucleotide substitution, where at a particular 
position in the genome one of the nucleotides is replaced by one of the 
other three nucleotides.  In humans it has been determined that between 
generations approximately one out of one billion base pairs is substituted 
in this manner, for an average of three new germ line mutations carried by 
any given individual.  I will let you figure out what that averages out to 
in new germ line mutations per minute given a 25 year average generation 
time in humans, but I guarantee that it's a really small number.

However, the number of new mutations in the germline is only the number of 
new mutations in the lineage of the single germ line cell transmitted to 
the next generation.  What about all of the other cells making up the 
adult's body?  Given that the adult human body has somewhere between 
between 10 and 50 trillion (10^12) cells, there are approximately 43-45 
cell divisions between the fertilized egg and the adult human (2^43 is 
approximately 10 trillion).  Assuming 15 trillion cells, if each cell 
carried 3 independent mutations it would add up to a total of 45 trillion 
somatic mutations.

However, not all somatic mutations are independent.  Mutations which happen 
early in development are propagated to many progeny cells while mutations 
which occur late in development are shared by very few cells.  If there are 
only three mutations total per cell in the 45 cell divisions in the 
development of a human, the mutation rate is approximately one new mutation 
every 15 cell divisions.  It takes 30 trillion cell divisions to give rise 
to 15 trillion cells, so a total of (30/15) = 2 trillion independent 
mutation events would account for the three mutations seen per cell.  Given 
that there are only ~13 million minutes in 25 years, the average number of 
mutations per minute over a 25 year old's life is ~350,000, which seems 
like a lot until you average it out across trillions of cells.

It's important to note that I made a lot of assumptions in the preceding 
calculations, including straightforward ones such as 15 trillion cells per 
human.  The more important assumptions I made are that (1) all cells have 
the same mutation rate as the germ line, and (2) all cells have a similar 
number of cell divisions in their history.  Some cells have much higher 
mutation rates due to environmental factors, such as skin cells exposed 
to UV light.  Also, some cells are constantly replenished (like blood 
cells) and therefore experience more cell divisions than the germ line.  So 
350,000 somatic mutations per minute is really just a ballpark estimate, 
dependent on the assumptions above.

It's interesting to note that the human genome is only 3 billion base pairs 
in size, so if 2 trillion nucleotide substitutions occur then each and 
every nucleotide in the genome is likely to be mutated at least once.  
Fortunately, even germ line changes at most positions in the genome have no 
discernible effect, so somatic changes affecting only a few cells are even 
less important.

  Chris Carlson
  peterpan@mbt.washington.edu