How rare are mutations?

And how much do they influence geographic variation in populations?

Mutations and mutation rates: basic info

A mutation occurs when DNA is not replicated correctly during meiosis when gametes are produced.   At least one base-pair of DNA changes or is deleted or inserted.   The rate of mutation is the proportion of offspring that inherit a particular change each generation.   For instance, a mutation rate of 10-5 means that one in 100,000 offspring inherit a particular mutation from one of its wild-type parents.

Rates of mutation differ from place to place in the genome of any species, but measurements of mutation rates usually fall in the following ranges (the following figures are widely available, for instance on wikipedia):

10-4 - 10-6 / locus / generation
(one phenotype-changing mutation at any one locus every 10,000 to 1,000,000 generations)

10-8 / base-pair / generation
(one mutation at any one base-pair every 100,000,000 generations)

  • Remember that a locus (also called a gene) is the sequence of base-pairs coding for a protein (or often several proteins as a result of alternative splicing).   Also remember that two copies of a locus (gene) that differ in one or more base-pairs are called alleles.

  • The mutation rate per locus is higher than the mutation rate per base-pair because changes at many different base-pairs can make a phenotype-changing difference in any one locus.

    So mutation is a very rare event ... in any one gene ... in any one individual.

    But each individual has a lot of genes ... so what is the chance that any one individual has a mutation somewhere in its genome?

    And a population can contain a lot of individuals ... so what is the chance that a population has a mutation in any one gene in at least one individual?

    How many mutations does an individual have somewhere in its genome?

    Humans (and probably many other vertebrates) have some 3 x 109 base-pairs in each set of homologous chromosomes (or twice that number in the entire genome).   About 1.5% of these base-pairs constitute all the coding sequences (genes) -- about 45 x 106 base-pairs.   These coding sequences comprise about 20,000 genes.

    Because every individual has two copies of these 20,000 genes, a mutation rate of 10-4 would mean that each individual is likely to inherit about 4 phenotype-changing mutations somewhere in its genome.

    Even with a mutation rate of 10-6, one in 25 people are likely to have a phenotype-changing mutation somewhere in their collective genomes.

    How many mutations occur in the US each generation?

    The current population of the United States is about 300,000,000 people -- or 600,000,000 sets of homologous chromosomes (haploid genomes).   So at every protein-encoding locus in the human genome there are likely to be between 600 and 60,000 phenotype-changing mutations every generation (depending whether the average mutation rate is 10-6 or 10-4).

    Across the entire genome (with its 20,000 genes), in the US population there are likely to be about 107 to 109 phenotype-changing mutations each generation -- 10 million to a billion mutations in this one population.

    As mentioned above, there are about 45 x 106 base-pairs in all coding sequences (genes) combined, of which about 2/3 are not synonymous (so they result in changes in amino acids in proteins) -- some 30 x 106 non-synonymous base-pairs in genes.   So in every generation in the US population, every non-synonymous base-pair in coding sequences of the genome is likely to mutate 3 to 300 times (depending on the mutation rate).

    Mutations and geographic variation in populations

    We can thus conclude that in a very large population every possible phenotype-changing mutation could occur every generation!   Nevertheless, even in such large populations, the distribution of these mutations (the number and nature of mutations at each base-pair) will differ from population to population.

    In smaller populations (3000 or 30,000 or even 3,000,000 individuals) every possible phenotype-changing mutation is not likely to occur each generation.   Nevertheless, there will be a lot of mutations each generation at random places in the genome.   Because of the randomness of mutation, different ones will occur in different populations.