Question

Why does the mutation rate differ between autosomes and X-chromosomes?

Answer 1

In humans, each cell normally contains 23 pairs of chromosomes. Only one of these pairs - the sex chromosomes - differs in men and women. If you are biologically a woman, you inherited one X chromosome from your father and one from your mother. If you are biologically a man, you inherited one from your mother and a Y chromosome from your father.

Like all other chromosomes, the X chromosome carries genes that are used to create proteins that go on to produce observable traits. This happens through the process of transcription, in which a single strand copy of the DNA is made, which is then decoded into a protein. When a gene is processed like this it is said to be 'expressed'. Essentially, gene expression interprets the genetic information stored in DNA, converting it into traits.

In the 1980s, a study predicted that the genes on X chromosomes should be prone to evolve to be switched on in only one of the two sexes, making them different. This could explain certain biological differences between women and men. And when new mutations happen on X chromosomes their effects in women are subject to selection twice as often as their effects in men. So a mutation that is beneficial in women but harmful in men could nonetheless persist.

Unlike all other chromosomes, one of the two X chromosomes in women is inactivated in nearly all cells. It also has an extremely low mutation rate and (most perplexingly) the genes that are found on it are active in relatively few of our tissues.

The mammalian X chromosome could make an excessive contribution to the yield of deleterious mutations because of monosomy in males. Hence, McVean and Hurst (1997) proposed that selection would favor a lower mutation rate on the X chromosome and presented supporting data from mouse- and rat-sequence divergence.

Intuitively, the rate of mutations per genome seems likely to be determined by a trade-off between the benefits of reducing the deleterious mutation rate and the cost of increasing fidelity.The X chromosome spends only one-third of its time in males, versus half for the autosomes. Therefore, the overall mutation rate of the X chromosome should be lower than that of the autosomes, when the male:female ratio of mutation rates is >1.