Are recessive, deleterious alleles less common on the X chromosome than the autosomes in humans?

Question

As there is a potential for them to be more readily purged in hemizygous males (and in cell lineages in females with the deleterious-allele-bearing chromosome activated), I would expect the frequency of deleterious alleles to be lower on this chromosome than in autosomes. Is this information known?

Answer 1

Good question! Yes, this is correct: recessive, deleterious alleles are less common on the X chromosome than the autosomes in humans. Why is this?

We have 23 pairs of chromosomes. We get one chromosome from each biological parent (ex: we have one chromosome 5 from biological mother and one chromosome 5 from biological father). Males and females have two copies of every gene on the autosomes (chromosome pairs 1-22). The 23rd pair of chromosomes are called the sex chromosomes. Females typically have XX chromosomes, and males typically have XY chromosomes. Why does this matter? Let's first talk about recessive conditions, then talk about how chromosomes matter:

When someone is affected with a recessive condition on an autosome, both copies of the gene are mutated and not working correctly. However, when someone is a carrier of a recessive condition on an autosome, one copy of the gene is mutated and the other is functioning correctly. This carrier typically will not exhibit symptoms of the condition because they have a working back-up copy of the gene. This back-up copy is essential. If the back-up copy didn't exist, the mutation would have more deleterious effects. Thus, fewer people would carry the condition because most likely, it would shorten one's lifespan.

The number of gene copies is why recessive alleles are more common on autosomes than X chromosomes. While females have two X chromosomes, males only have one. That means that a male with a deleterious mutation on an X chromosome has no working backup copy. Thus, they experience the recessive disease with a much higher frequency than a female would. Males don't have a back-up copy like females do.

So, if half the population (males) experience a shorter lifespan due to an X chromosome mutation, we would expect those males to reproduce at a lower frequency. Thus, these deleterious mutations are less common on the X chromosome than the autosomes in humans.