Is mutation random?
Is mutation random?Mutations in DNA are clearly probabilistic, but they aren't random. Many factors determine the rate of accumulation of mutations. The simplest is polymerase error rate (chemistry). An average of more that a few errors per generation will be fatal to an organism. Surprisingly, mutant polymerases with reduced error rates are selected against. This implies that a basal error rate is essential for evolution (long term survival) or that decreased error comes at the expense of slow replication.
DNA Polymerase error rates are not uniform. They depend on context of the DNA sequence. Presumably organisms have some flexibility to adjust DNA sequences to reduce error rate, but this comes at the expense of reducing the flexibility of the sequence to perform other functions.
There are many other types of "errors" in addition to simple "missense" errors. These include insertions, deletions and rearrangements. These range from single nucleotides in scale to chromosome rearrangements which can be observed by classical microscopy. On the one hand such changes can be fatal, on the other, they can be essential to survival (as in the adaptive immune system.)
DNA damage from chemicals and radiation also affects mutation rate. Cells have repair mechanisms. Efficiency and accuracy of repair mechanisms likewise affect mutation rate. Repair mechanisms can differ in different parts of the genome. Highly conserved genes will be in regions of efficient repair. Genes (e.g. immunoglobulin genes) for which variation is advantageous will be in regions of error prone repair. Natural selection favors genes "settling" in regions of appropriate error rate.