Why does inbreeding cause genetic defects, but cell division in one's own body does not?

Question

I was watching a DNA transcription video when I realized that cells basically create copies of DNA all the time in our body. There may be a few mutations/errors, but it works out fine. However, when the haploid DNA in sperm combines with the one in the egg, there's so much extra work to be done to avoid errors. It's like if I write some software in one project and try to combine it the code I've written in another project, it's easier for me to do it because my coding style is similar and I know the code. But if I have to merge somebody else's code into my code, there would be a heck of a lot of merge conflicts and errors. Sure, I may learn better programming from the other person's efficient code, but the amount of bugs, testing etc. will be much more cumbersome.

Some research says:

Malformations or harmful traits can stay within a population due to a high homozygosity rate, and this will cause a population to become fixed for certain traits, like having too many bones in an area, like the vertebral column of wolves on Isle Royale or having cranial abnormalities, such as in Northern elephant seals, where their cranial bone length in the lower mandibular tooth row has changed. Having a high homozygosity rate is problematic for a population because it will unmask recessive deleterious alleles generated by mutations, reduce heterozygote advantage, and it is detrimental to the survival of small, endangered animal populations. When deleterious recessive alleles are unmasked due to the increased homozygosity generated by inbreeding, this can cause inbreeding depression.

But bed bugs for instance, have managed with inbreeding without any problem (goddamned creatures!).

The question I'm asking is from the perspective of how the DNA combination and copying happens. Since the regions chosen during meiosis is random, shouldn't a similar DNA from sperm and egg resulted in a more stable genetic code since they are similar? I'm not looking for simplistic answers like "because Nature wanted diversity" or "because recessive alleles are unmasked".

I'm looking for a more fundamental explanation about the property of DNA, or the process of copying/merging these complex structures. Why does merging two similar things cause more problems than merging two dissimilar things?

Answer 1

I suspect your problem is grasping what is a deleterious recessive allele. Wikipedia and textbooks explain it much better but I will try to illustrate with respect to your question.

I have to merge somebody else's code into my code, there would be a heck of a lot of merge conflicts and errors.

Problem with this analogy is that when merging code both variants are written by people. People tend to write code that works on its own. This is not the case for DNA since mutations are usually random and more often than not result in gibberish. Better analogy would be maybe combining information from two coppies of the same data to overcome bit rot.

Since the regions chosen during meiosis is random, shouldn't a similar DNA from sperm and egg resulted in a more stable genetic code since they are similar?

Lets consider two made up genes A and B.

• A is a dominant functional version of A gene involved in development of hand. In very abstract (code-like) way it could be read as: "If at the end of hand initiate 5 fingers"
• a is a mutated nonfunctional version of A gene. In very abstract way it could be read as: "If at the end of hand initbzngers". It produces nonfunctional protein. In biological terms "a" is called deleterious recessive allele.
• B is a dominant functional version of B gene involved in development of brain. In very abstract way it could be read as: "If in neuron keep junctions together"
• b is a mutated nonfunctional version of B gene involved in development of brain. In very abstract way it could be read as: "If in geuron keep junctions together". It never produces the needed protein.

Now lets consider cross between two dissimilar individuals:

father AaBB X mother AABb

Following Mendel's laws they produce progeny:

• AABB - has at least one functional copy A and B gene and thus develops fine.
• aABB - has at least one functional copy A and B gene and thus develops fine.
• AABb - has at least one functional copy A and B gene and thus develops fine.
• aABb - has at least one functional copy A and B gene and thus develops fine.

now let's consider cross between two similar individuals:

father AaBB X mother AaBB

Following Mendel's laws they produce progeny:

• AABB - has at least one functional copy A and B gene and thus develops fine.
• AaBB - has at least one functional copy A and B gene and thus develops fine.
• aABB - has at least one functional copy A and B gene and thus develops fine.
• aaBB - fails to properly develop fingers.

cells basically create copies of DNA all the time in our body. ... Why does inbreeding cause genetic defects, but cell division in one's own body does not?

During normal cell division AaBB cells should produce only AaBB copies which have at least one functional copy A and B gene and thus are fine.

Big picture

In a real population imagine every individual has tens of thousands of genes and each of them can be made nonfunctional by random mutation. The nonfunctional copy often does not have effect since the individual has another functional copy. When two non-related individuals procreate, chances are mutations they carry are in different genes and their progeny are fine as illustrated above. When related individuals procreate chances are thay both have the same deterious mutation(s) and not all their progeny will be fine.

But bed bugs for instance, have managed with inbreeding without any problem (goddamned creatures!).

Species for which inbreeding is normal have much less recessive deleterious mutations prevalence in populations for simple reason. If new deleterious mutation appears the inbreeding leads in two generations to aa homozygots that die or fail to procreate and the "bad" mutations are selected out fairly fast. Inbreeding is normal state for some species. Today inbreeding-resistant species are descendants of individuals who have survived many generations of inbreeding.

Answer 2

You say

cells basically create copies of DNA all the time in our body. There may be a few mutations/errors, but it works out fine.

and

Why does merging two similar things cause more problems

Well, it doesn't, at least not in the way you seem to understand it. Cell division in the adult human leads to problems too. Every time a cell of yours divides, there is a chance that something goes wrong and the new cell receives an imperfect copy of the DNA. This is what is called a "somatic mutation" (the opposing term would be "germline mutation"). This is the reason people get cancer - when you are unlucky enough that a cell of yours gets all its anti-cancer mechanisms get mutated away, it can become the "granddaddy" of a tumor in your body. It (and its descendents) start multiplying exponentially. And of course, there is even more mutations in this large number of new divisions, which makes for subclonal tumors, complete with a perfidic kind of natural selection when exposed to some of the newer targeted therapies we have. So this kind of mutation happens frequently, and it does lead to quite large problems for individuals and for humanity as a whole.

The problems with inbreeding also exist, they are just a different kind of problem with a different cause and effect. Here, what you are afraid of is not a mutation. Rather, as explained in more depth in the other answers, if the father has one good and one malfunctioning copy of a gene, and the mother has one good and one malfunctioning copy of the same gene, you get very high chances of having a baby with two malfunctioning copies of that gene, without any transcription errors coming into play at all. And it is very rare for this to happen if you randomly select a mother and a father from the population, but if the two of them share a significant proportion of their genes (because they are related), it happens fairly frequently - enough for basically all human societies to have noticed it even in ancient times and to have created taboos around inbreeding.

A third thing can also happen, which is a de novo mutation in the very early stages of cell division of the zygote. It is not necessarily a result of merging the genomes of the mother and the father, but rather a cell division problem after this merging has happened. It is not necessarily more rare, per division event, than the somatic mutations (the first kind of problem). But it will affect all the cells emerging from that mutated cell, which will be a significant proportion of the baby's body. This is an event that is not very noticeable, since many of the problems at that stage will not result in a life birth - in fact the pregnancy/conception can end so early that the mother never realizes she conceived. It is also not as prominent in social norms, since it is not correlated to something obvious like inbreeding, so there are no traditional prohibitions for events that lead to it (actually, there are modern prohibitions, like warnings in situations which can cause mutations in a fetus or a zygote).

All three of these exist, and all of these lead to problems. So your wondering why one is a problem and the other isn't is based on a misunderstanding.

Answer 3

Why does inbreeding cause genetic defects, but cell division in one's own body does not?

Inbreeding does not cause genetic defects, it just makes already existing ones more likely to be problematic.

Why does merging two similar things cause more problems than merging two dissimilar things?

You have two copies of each gene, one from each parent. For many possible defects all that matters is that you have at least one working copy, which can compensate for the other not working. If you take two parents that each have a bad copy because they inherited from a common ancestor, there is a high likelihood that their children will receive two bad copies, and thus the previously hidden defect will be expressed.

I'm looking for a more fundamental explanation about the property of DNA, or the process of copying/merging these complex structures.

The fundamental part is just that you have two complete copies of your genome, one from each parent. If you didn't, inbreeding would be much less of a problem.