Why would lethal genes evolve?

Question

I've been reading through 'The Selfish Gene' by Dawkins. At a few places in the book he states that incest is damaging because it would give a very high chance of lethal recessive genes becoming active due to the high probability of both children having the gene compared to one child and one stranger from the same species.

However, this leaves me with the question why lethal genes would evolve in the first place. The only reason I can think of is that these genes have some secondary purpose and survive natural selection because of that.

Is this simply the entire story or are there things that I'm missing? It seems to me that the having possibility of getting healthy offspring from incest is beneficial to a species, if only because finding a mate would be easier, so those secondary effects would have to be pretty good.

Also I'd be curious if any research has been done which has found examples of side effects of these lethal genes that would make them preferable.

Answer 1

Lethal genes evolve simply because of random deleterious mutations and absence of strong selection.

Recessive lethal genes

Random mutations can make a gene product non-functional or reduce its activity. However, in diploid organisms the other fully-functional copy of the gene can compensate for the non-functional allele.

Sometimes both the alleles can carry different mutations which can lead to complementation; this would not affect the gene activity. Also see: Explain allelic complementation at molecular level. Let's not consider this case here.

So, the fitness of the heterozygotes would not be affected and they will continue to propagate. However, if both the alleles are affected then it would lead to lethality (or lets say reduced fitness). This can happen if two heterozygotes (with the same deleterious mutation) mate and give rise to a homozygote (with both the alleles affected). Since siblings (or other close kins) are genetically related, there is a good likelihood that both of them may be carrying a copy of a non-functional allele and homozygous offspring born out of such a mating may have reduced fitness.

Dominant lethal genes

There are some cases of dominant lethal alleles. Examples include the mutated genes responsible for Huntington's disease (or similar poly-Q disorders). Other examples include a mutant allele of a proto-oncogene that leads to its hyperactivity (and therefore cancer).

Dominant lethal alleles persist in the population primarily because of their late onset. In such cases an individual with such an allele would have already mated and produced offspring before the disease kills them.

Other reasons for the persistence of lethal genes

Another possibility (applicable to the case of cancer) is that the mutations are not in the germ cells and were acquired by somatic cells because of some external agent. These mutations would not be transmitted to the next generation.

Sometimes, the deleterious nature of the allele can exert its effect only under certain conditions. Let's say someone has a mutation that causes reduced immunity. Such a person would survive well if they remain in a sterile environment. In general, we can say that there is no strong selective pressure against the mutation.

Sometimes the reduced fitness because of a mutation under a certain condition can be overwhelmed by an increased fitness caused by it under some other condition. A very well known example is that of the haemoglobin allele that causes sickle-cell anaemia. However, the RBCs in the individuals affected by this disease are resistant to infection by the malarial parasite. The mortality due to malaria is much higher than that due to sickle cell anaemia. Therefore, in regions where malaria has high incidence (like Africa) this allele is positively selected.

Answer 2

This is just loose terminology. By ‘lethal gene’ Dawkins means an essential gene with a mutation that renders it inactive. With a recessive gene, the one ‘good’ copy in the heterozygote provides enough gene-product to allow survival, in contrast to the situation in the homozygote where the total absence of gene-product is lethal.

With a rare mutation, the chances of two unrelated individuals being heterozygotes is small. However within a family, the chances are much higher. One sees this, for example, in inbred animals such as thoroughbred dogs.

Such recessive genes normally stay rare, and do not ‘evolve’ — there is no selective pressure to maintain them and they are lethal in the homozygote. Only in cases where there is some advantage to carrying only one copy of the gene is the heterozygote selected for. Examples of this are sickle-cell anaemia and beta-thalesaemia where the protection against malaria is provided in the heterozygote. (But I don’t think Dawkins mentions this.)

Answer 3

It would be beneficial to a population for a lethal gene to evolve in incestuous situations because genetic diversity is then promoted through natural selection. Genetic diversity is necessary for a species to evolve which would improve the chance of survival.

Answer 4

They occur because there is no reason for them to be selected against. Except for a 25% chance of offspring not surviving, in the rare event that the other parent also has the mutation.

That recessive, lethal genes can persist in the population is surprisingly one of the reasons that diploid organisms that sexually reproduce are so successful and diverse. Diploidy means there are two copies of each gene, and that a mutation in one gene that doesn't immediately increase fitness won't necessarily be removed from the population. Even if it would be down right fatal if it occurred in both genes. Because its function can often be covered by the other, normal gene.

It might appear that a carrier of this mutated gene might be less fit to produce healthy offspring. But most organisms create many more offspring than can actually thrive. And what first appears to be a 'weak gene' can later go on to be the basis for a better mutation, often through recombination during meiosis of parts of the lethal gene with its normal counterpart.

In general this is one of the reasons that eukaryotes are so diverse. Because they have many mechanisms like this that don't only protect from mistakes in DNA, they often enable them to be beneficial.

Another such mechanism is that eukaryotes have a lot of introns in their DNA that are removed from their messenger RNA before it is translated into protein. This means that any random chunk of DNA integrating into their genome (a reasonably frequent event, evolutionarily speaking) is less likely to cause gene inactivation and more likely to simply be incorporated. Into an existing gene or even actually added as an extra gene. This encourages a very modular organisation of genes, gene regulation and proteins by enabling the evolution of functional motifs that are reused over and over again.