Question

In human genomes, the per nucleotide mutation rate is estimated to be about 2.5 x 10^-8. Let us consider a recessive lethal genetic disease caused by a single point mutation. We will name the allele produced by this point mutation L, and the wild-type allele W. Let us further assume that the disease phenotype expressed by LL individuals always kills those who have it before they reproduce. What would you predict the equilibrium frequency of the allele L be in the population after many generations? (You may assume Hardy-Weinberg equilibrium except for mutation and selection, and you may assume as an approximations that back-mutations from L to wild-type are rare enough to be ignored).

Answer 1

Genotype	WW (wild type)	WL	LL (lethal)
Initial zygotic freqs.	p2	2pq	q2
Fitness	w11 = 1	w12 = 1	w22 = 1 - t

Solve with genral selection model : q =  

At first Selection against allele L will be very effecient, but progressively it becomes slower, because a larger proportion of the recessive allele (L) will be protected in heterozygoous form (WL) as the allele frequency decreases . Therefore, natural selection alone cannot entirely eliminate the recessive allele, even if it is lethal.