|MadSci Network: Genetics|
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 email@example.com
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