What Is a Mutation?
There are basically three ways to estimate the mutation rate in the human lineage. I refer to them as the Biochemical Method, the Phylogenetic Method, and the Direct Method.
The biochemical method relies on the well-known fact that the vast majority of mutations are due to errors in DNA replication. Since we know a great deal about the replication complex and the biochemistry of the reactions, we can calculate a mutation rate per DNA replication based on this knowledge. The details are explained in a previous post [Mutation Rates]. I'll give a brief summary here.
The overall error rate of DNA polymerase in the replisome is 10-8 errors per base pair. Repair enzymes fix 99% of these lesions for an overall error rate of 10-10 per bp. That means one mutation in every 10 billion base pairs that are replicated.
The human haploid genome is 3.2 × 109 bp. [How Big Is the Human Genome?] [How Much of Our Genome Is Sequenced? ]. That means that on average there are 0.32 mutations introduced every time the genome is replicated. In the male, there are approximately 400 cell divisions between zygote and the production of a sperm cell.1 This gives a total of about 128 new mutations in every sperm cell. In the female, there are about 30 cell divisions between zygote and the production of egg cells. That's about 10 new mutations in every egg cell.
Adding these together gives us about 138 new mutations in every zygote. Let's round this down to 130. Thus the estimate from the Biochemical Method is ..
130 mutations per generation
[Image Credit: Wikipedia: Creative Commons Attribution 2.0 Generic license]
1. This depends on the age of the man when he has children. The value used here is approximately the average for a 30 year old man.