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Feedback archive → Feedback 2017

Mutations, and why you shouldn’t marry your cousin

Some of the most interesting questions our ministry receives deal with the subject of genetics. It is an exciting, relatively new field of science, and many people want to know how it impacts our understanding of creation. Today we feature two genetics questions with responses from Dr Robert Carter, CMI-US

Milla R. from Australia writes:

Hello. I read your interesting article about interracial marriage, and I read about how you mentioned that interracial couples’ kids are likely to have greater genetic variety, then kids of couples of the same ethnic groups. Does this mean that it’s wrong for two people of the same ethnic group to marry?

Thanks and God bless.
iStockphoto family

Dr Robert Carter responds:

Milla,

An excellent question!

The answer is, “No.”

Here’s the explanation: Let’s say a recessive mutation exists in one out of every thousand people in a population (this is an extreme example, most mutations are not nearly that common). If two random people marry, we can factor in the chance that they both carry the mutation and the chance that they will both pass the mutation to the child:

1/1,000 x 1/1,000 x 1/4

Thus, the probability of a child being born with that mutation = 0.00000025, or 0.25 children out of every million. That number is approximately zero.

multation 
Figure 1: The probability of appearance for a recessive mutation with a frequency of 0.001 (1 out of 1,000 people are carriers) per million babies. Different degrees of relatedness are calculated. The probability of a child being born with two copies of a recessive mutation falls rapidly toward the background level (“unrelated”) as the degree of relatedness goes down. This is an extreme example because most mutations are not nearly this common.

We can calculate these probabilities for any degree of relatedness. For example, if an uncle marries his niece (or an aunt her nephew), there is a 25% probability (1/4) that any mutation carried by one is also carried by the other. Thus, 1/1,000 x 1/4 x 1/4 = 0.0000625, or 6.25 out of every 100,000. The risk is 250 times greater than if two unrelated people marry. Of course, we’re still only talking about 0.00625% of babies from uncle/niece marriages would be affected, even with this extreme example.

For any particular mutation, the risk of an inbred child carrying it is relatively low. But there are many thousands of deleterious mutations circulating within every population. Thus, the true inbreeding risk is significantly greater than the risk for a single mutation.

If two people from very different racial backgrounds marry, the chance that both carry the same recessive mutation is much lower, so the probability of a child carrying two copies of a deleterious recessive mutation is extremely low. Yet, so was the probability from two random people in the same population marrying.

Take home point: just don't marry your cousin.

Thanks for the enjoyable mathematical exercise. I hope it made sense to you.


Bill H. from the United States writes:

Dear Dr. Sanford. My wife and I are reading your new book and we are enjoying it immensely. I am also debating a biologist who disagrees with your mutation rate calculations and cites the following article as his reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276617/

I'm not a biologist but a retired engineer. Any help you can give me regarding this would be most appreciated.

God's Blessings

Dr Robert Carter responds:

Bill,

I am answering for Dr. Sanford since he is not employed by CMI.

Ah yes, Peter Keightley.1 I follow his work and have learned lots from him. Here, however, I think he is applying too much wishful thinking to his studies. First, the true mutation rate is still unknown. Older estimates were higher than some of the more recent ones. Some of the lower values come from studies performed on the Icelandic population. That country decided to jump feet-first into the world of genomics and we thus have a LOT of data for Icelanders. Problem is, this is a small, inbred country and it is not at all clear that their results can be generalized to the entire world. It is doubly unclear if they can be generalized though all of human history. But there are other sources of low mutation rates he could be using.2 Personally, I have been very frustrated by the information being provided by sequencing programs. Take the 1000 Genomes Project. They sequenced more than 2000 people, but the genomes are “low coverage”, in other words “high error rate”. One cannot use their data to measure the real mutation rate because the error rate approximates the expected mutation rate. This is something that I very much want to know and the fact that he assumes he has an accurate estimate is more than a little annoying. There is more “art” than “substance” here.

Second, he says the rate from these studies is lower than the one estimated by evolutionary assumptions. This is very convenient for him. Everything in the past was suggesting that the real, measurable rate was much higher than evolutionary rates. Also, they have pushed back the human-chimpanzee split from 3 million years ago (when I was in graduate school just over a decade ago) to more than 6 million years ago, and some are arguing for more than that. This directly affects the evolutionary “rates”. So they cite the lower mutation rates while failing to mention the many caveats associated with the estimates. The real rate is an unresolved issue, and the fact that they want it as low as possible should make us suspicious.

Third, notice how he bases his estimates on “a method proposed by Kondrashov and Crow”, which we might construe as an ‘appeal to authority’. They, in turn, are making assumptions about the “mean selective constraint per site”. This is a hugely controversial issue. Sanford has taken great pains to measure the selection coefficient. I am not familiar enough with Kondrashov and Crow’s method to compare the two, but I am certain they are making assumptions in favor of evolution.

He then admits that his final, downward-skewed rate is 2.2 deleterious mutations per generation. This is 20 times higher than Haldane’s worst case estimate that would guarantee human extinction, and Haldane’s estimate is woefully low.3 To solve this, Keightley appeals to unknowns, specifically different models of selection (which have be studied with Mendel’s Accountant) or synergistic epistasis (which the link will show does not do what he thinks it does). I know this was not the focus of his paper, but he still has not conquered the ultimate bugaboo: the increase of beneficial mutations required by evolution.

In summary, while Keightley is a well-known scientist and does decent work in many areas, in this case he is clearly attempting to wish away the problems he knows exist. He knows the mutation rate is too high and appeals to unknowns to solve the problem.

What do you tell your friend?

  • 1. The estimate is based on many, many assumptions.
  • 2. The estimate is still too high.
  • 3. Appealing to unknown processes is wishful thinking. Worse, those unknown processes are not actually unknown. They have been studied, and quantified, and they fail to solve the problem. Worse, the real problem of how to make people better over time is not even being discussed here.

Dr John Sanford responded further:

The Keightley paper says that the point mutation rate (designated “u”) is 70 point mutations per person per generation. This is in the ball park of what I have been saying all along. But he also calculates the rate of deleterious (non-neutral) mutations (designated “U”). He comes up with 2.2 deleterious mutations per person per generation. This is simply because he is assuming most mutations are neutral, in other words he believes most mutations arise in the “junk DNA” portion of our genome. The recent ENCODE findings show that most of the genome is functional, but Dr. Keightley is in denial of this new understanding, and so assumes only a few percent of the genome is functional.

For various reasons, I think 70 is still on the low end. There are numerous papers now saying 100, including Lynch’s newest paper.4 But even if the mutation rate was 2.2, my arguments hold.

Related Articles

Further Reading

References and notes

  1. Keightley, P.D., Rates and fitness consequences of new mutations in humans, Genetics 190:295-304, 2012. Return to text.
  2. He cites a value of 1.1x10-8 mutations/bp/generation. Multiplying by the approximately 3 billion nucleotides in the genome, then accounting for the fact that each cell has 2 copies of the genome yields 1.1x10-8 x 3x109 x 2 ≈ 70 (66, actually). Return to text.
  3. Rupe, C.L., and Sanford, J.C., Using numerical simulation to better understand fixation rates, and establishment of a new principle: Haldane’s Ratchet, Proceedings of the Seventh International Conference on Creationism. Pittsburgh, PA: Creation Science Fellowship, 2013. Return to text.
  4. Lynch, M., Mutation and human exceptionalism: our future genetic load, Genetics 202:869–875, 2016. Return to text.

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