Wednesday, March 20, 2013

Estimating the Human Mutation Rate: Phylogenetic Method

This is the third in a series of posts on human mutation rates and their implication(s). The first two were ...

What Is a Mutation?
Estimating the Human Mutation Rate: Biochemical Method

There are basically three ways to estimate the mutation rate in the human lineage. I refer to them as the Biochemical Method, the Phylogenetic Method, and the Direct Method1.

The phylogenetic method relies on a known phylogenetic tree to pick out close relatives and the approximate time to the last common ancestor. In the case of humans, we know that chimpanzees and bonobos are our closest cousins and we think that the homind line diverged from the chimp line about 5 million years ago.

If we count mutations in chimps and humans we can assume that these mutations have been accumulating since the time of the last common ancestor. This can be converted to a mutation rate if we know that the mutations are neutral. That's because, according to population genetics, the rate of fixation of neutral alleles by random genetic drift is equal to the mutation rate.

Many studies have been done to estimate the mutations rate in the hominid lineage. I'll just mention two to illustrate the principle.

Nachman and Crowell (2000) looked at silent mutations in eighteen pseudogenes common to chimps and humans. They found a total of 199 substitutions in 16,086 nucleotides. Converting this to a mutation rate requires several assumptions. If we assume that equal numbers of mutations occurred in each lineage (~100) then the mutation rate works out to ~2.5 × 10-8 mutations per nucleotide. This calculation depends on the time since divergence (~5 million years), the generation time (they assumed about 25 years), and to some extent the population size (about 10,000).

That mutation rate corresponds to 160 mutations per diploid genome per generation.
160 mutations per generation
This is more than the 130 mutations per generation estimated by the biochemical method.



-mutation types
-mutation rates
You can also calculate a mutation rate from the total differences in the (almost) complete sequences of the human and chimpanzee genomes. The human genome is a finished genome so it's quite reliable. The chimp genome is less reliable but good enough to gives us a ballpark estimate. The differences (substitutions and small deletions only) amount to 1.4% of the genomes or 44.8 million mutations.

Assuming that equal numbers of mutations occurred in each lineage this gives 22.4 million mutations that have become fixed in the human lineage since diverging from our common ancestor with chimpanzees.2 If the species diverged 5 million years ago and the generation time is 25 years then this gives a mutation rate of 112 mutations per generation.
112 mutations per generation
This is a bit less than the 130 mutations estimated by the biochemical method.

These mutation rates depend on the time since divergence or the time of the last common ancestor. In the case of chimps and humans, the estimate of 5 My is roughly compatible with the fossil record but the date is not well established by fossils. There's still some controversy. Many scientists think that the date should be older. If the two lineages diverged 6 My ago, then the mutation rate would be 93 mutations per generation.

The rate also depends on estimates of generation time. Human generation times are consistently underestimated compared to the actual data on modern humans. The data indicate an average generation time of 30 years and that's consistent with genealogical studies (Langergraber et al., 2012).3 Chimpanzee generation time in the wild averages 25 years (Langergraber et al., 2012).

The longer the generation time the higher the mutation rate. But differences in the generation time between chimp and human lineages means that more mutations are fixed in the chimpanzee lineage that the human lineage and this reduces the calculated mutation rate.

Using the phylogenetic method, we may not be able to calculate a precise mutation rate for humans but most of the values seem likely to be in the range of 100-150 mutations per generation and that's similar to the mutation rate calculated from our knowledge of biochemistry and molecular biology.

[Image Credits: The phylogenetic tree is from Locke et al. (2011)]. The chimp photo is from Wikipedia]

1. The traditional estimates were based on the analysis of the frequency of new disease loci in human populations. The classic paper by Haldane (1949) is now available online. The problem with those classic estimates if that most of the mutations were in hot spots—that's why they occur so frequently. Recently Kondrashov (2002) estimated the mutation rate from 20 disease loci that appear to arise from "normal" mutation rates. His estimate is 115 mutations per generation a value that's consistent with both the biochemical rate and the phylogenetic rate.

2. There are probably fewer mutations in the human lineage because the generation times were a bit longer. Not all of the differences are due to mutations that have become fixed in the chimp and human populations but this is probably a small fraction of the 44.8 million differences.

3. My wife and I share a common ancestor who was born about 1350. We are 18th cousins and that gives a generation time of about 31 years.

Haldane, J.B.S. (1949) The rate of mutation of human genes. Hereditas 35(S1):267-273. [doi: 10.1111/j.1601-5223.1949.tb03339.x]

Kondrashov, A.S. (2002) Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Human mutation 21:12-27. [doi: 10.1002/humu.10147

Langergraber, K.E., et al. (2012) Generation times in wild chimpanzees and gorillas suggest earlier divergence times in great ape and human evolution. Proc. Natl. Acad. Sci. (USA) 109:15716-15721. [doi: 10.1073/pnas.1211740109]

Locke, D.P., et al. (2011) Comparative and demographic analysis of orang-utan genomes. Nature 469:529-533.

Nachman, M.W. and Crowell S.L. (2000) Estimate of the mutation rate per nucleotide in humans. Genetics 156:297-304.


  1. These are very nice, common language summaries. Very well done.

    One small edit - under the box with "112 mutations per generation" change;

    This is a bit less than the 112 mutations estimated by the biochemical method.


    This is a bit less than the 130 mutations estimated by the biochemical method.

  2. Okay.
    So genetics here is being used to draw a relationship between man and ape.
    Mr MOran.
    this yEC creationist on behalf of interested creationists everywhere asks you what GENETIC scientific evidence do you have to back up your claims here of trees or lineage between us or any creatures withe other creatures that are different types.
    All I see here is you saying there is like genetics and thats the PROOF of like biological descent.
    I'ts just a line of reasoning.
    It would be that way if God created creatures just as said in Genesis.
    Anyways its about science and using evidence.
    This is a good point for YEC creationism

    1. Please feel free to offer up any other explanation that fits with known facts and is consistent with the data.

    2. I like the so-called evidence of the macro-nii-evolution of the Darwin Finches. While Larry is not sure if they are the "real proof"--he thinks they are 50% macro-nii-deloutionists. I say 99% of DEvilOLUSIONISTS are the believers... So, that means it is just as good as blind faith...

    3. @Robert Byers
      2 weeks ago prof. Moran suggested there may be more than one (1) LUCA. I'm not sure of the status of his blood alcohol concentration at the time...Sorry

    4. 1. If you're a poe I apologize and complement you on your incoherence.
      2. This is a scientific study which means evolution is taken as fact because evolution is a fact from a realistic and empirical perspective. It isn't trying to prove evolution because that has already been done.
      3. Please explain how exactly this is good point for YEC (or any form of Creationism).

    5. I believe the main issue on this blog and beyond is definition of what evolution really is. Most creationists I know, don't deny micro-evolution-this is a problem depending where you look. Some DEvoLUTIONISTS say or believe that micro-evolution leads to the development of totally new species overtime.

      Now creationists know and understand that changes within a kind are acceptable however, these changes do not lead to the formation of new species. That is the difference.

    6. John, shut up already, your ignorance displayed with that prideful "style" makes you look like a complete ass-hole.

    7. Witton: I believe the main issue on this blog and beyond is definition of what evolution really is.

      The main issue on this blog is this troll infestation. As in the present case: the host starts a highly interesting and informative series of posts, and the next minute internet vermin begin to pollute the discussion with their verbal crap.

    8. A piece of advice. If (like me) you have been reading Byers' posts for several months and continually find that they make no sense at all - in addition to having atrocious spelling/grammar - here is something to help: locate places where the phrase "a line of reasoning" is used. Simply replace these words with "the way the evidence points" or "the truth", or "pretty obvious, really" ... and a little fragment, a small island of meaning, will then appear, amidst the rest of the nonsense around it. Yawn.

  3. Nice to see the correspondence between the two sources of evidence.

    You forgot to point out that a large proportion of mutations in functional regions are under purifying selection, which should lead to an underestimate - so we should expect the 2nd estimate to be lower than the 1st (which is indeed what we see).

    1. 112/130 = 0.86

      ~14% of the genome under selection.



  4. Larry: Were you able to estimate the human mutation rates either leading to androgenic alopecia--pattern baldness also called pattern hairloss--or Darwin forbid, to the prevention of the disorder. I'm sure you have not omitted this very important part of the puzzle for us but not for you....

    1. What? So god did or didn't sport the "landing strip" hair style?

    2. Who said God? Not me??? We are talking science now not religion you moron.

    3. Hey witless, are you saying that being a creationist has nothing to do with believing in and promoting a "God" and "religion"?

    4. Just a reminder; I'm not a creationist. I'm just sceptical about your faith--biogenesis and macroevolution.
      That's not all, but these are the main reasons...

    5. Of course you are a creationist, and your denying it makes you a liar too.

      What is it your book of magic says about lying?
      Oh yeah, here it is, supposedly directly commanded by the almighty itself: EXODUS 20:16 Thou shalt not bear false witness against thy neighbor.

      And here you are, apparently so dishonest you deny belonging to the very faith you're here propagandizing on behalf of.

      I've seen dusins of creationists like you. Lying for Jesus to try and get a foot in the door, the method more transparent than intergalactic void is to neutrino-radiation.

      TheOtherJim is right, you're nothing but an ignorant troll and should just be ignored.

    6. So now you are going to decide who I am, and what I believe in??? What if I believe in panspermia? Does that make me a creationist? If yes, put me in and call me a creationist along with Richard Dawkins...

  5. Please folks - Just ignore the troll.

  6. William Bell
    i think you were addressing me.
    The claims here for genetic relationship indicating common descent is a good case for creationist criticism.
    What is being done is a great conclusion of common descent of men/apes from a primate common ancestor from observing that we have like DNA.
    Then they say this counts as scientific genetic investigation and to oppose it is to be in a state of opposition to science.
    YEC crys foul at this.
    We say its not scientific genetic investigation but only a line of reasoning.
    Therefore another line of reasoning cancels out the first one and so the end of evidence.
    Lines of reasoning are not facts from scientific investigation.
    There is no genetic scientific evidence for common descent.
    Even if true there still isn't.

    1. Robert,

      Look at the tree in the post (above). That tree is constructed from comparisons of DNA sequences. The analysis is quite simple and the facts aren't in question.

      The molecular tree fits quite well with the fossil data and with the relationships that we deduce from anatomical and embryological data. They all agree that chimps and humans cluster together and that orangutans are further away.

      This data is explained by evolution from common ancestors and the dates are consistent with everything we know about the facts of microevolution (population genetics) and the biochemistry of mutation.

      What's your explanation for all these facts? Do you have one that accounts for the data or are you just closing your eyes, putting your hands over your ears, and shouting gibberish at the top of your lungs?

    2. Hey, I thought it was bad to feed Byers. And in fact he'll only post something incoherent in reply, so there's no point.

  7. Mr Moran.
    To make a case on genetics being evidence for genetics teaching a biological descent with primates one MUST use genetics.
    Fossil evidence, anatomy, embryology , are not admissible evidence for genetic investigation.
    Creationist ideas on the facts are beside thpoint right now.

    These rates of genetic drift are speculative as they were not observed .
    My point is that any DNA connection between man/ape or anyone is only be drawn from a line of reasoning that because we have like DNA it demands we are from a common heritage.
    Yet another line of reasoning, say from a creator working on a common blueprint for biology, would also allow for like DNA with like looking creatures yet unrelated by descent issues.

    Evolutionism is not imagining another option and then insists its conclusion on ape/man is based on investigation of genetics.
    My stress here is that this thread shows conclusions of genetic relationships is being presumed.line of reasoning from the simple , already concluded, idea that man/apes are related because of DNA .
    Always they tell me look at my father/me DNA and so PROOF of connection to apes.
    In fact its proof of just a line of reasoning and a lack of scientific genetic evidence.

    Where is the scientific genetic evidence for biological descent etc with primates??
    Not other "evidences"!
    Not just extrapolation backwards because of human example.
    The tree is extrapolation itself.
    I really think I got a good creationist point on this genetic evidence claims.

  8. Robert,

    you are spewing nonsense, and are an embarrassment to the church, to believers who actually think and know how to reason, and to anyone who spends even a moment examining the truly overwhelming scientific evidence that is present in the genetic record. Christian fundamentalism lost all intellectual credibility when it was formed back in the mid-19th century. Do your homework and read up on the reasons for it forming (and read both sides). It was formed (invented from whole cloth is a better way to put it) to deal with the fact that they had lost the intellectual battle. Fundamentalism was formed because they realized their worldview was coming to a crashing end as a natural outcome of the Enlightenment, the Industrial Revolution and the Scientific Revolution. You should study these revolutions--the documentation is already there. There is good documentation as early as he late 1800s that utterly destroys not some, but all, young earth ideas. It wasn't just a guy named Darwin--it was the entirety of the combined sciences of astronomy, geology, biology, physics, and chemistry. None of the arguments you are hauling out of the dustbin are new--they are just new to you because you are not learned enough to have reviewed the literature that is abundantly on record already. Learn and free yourself from this foolishness. While you are at it, compare your cosmology (what you believe about the cosmos, stars, rotation of planets, galaxies, and such) to what the Bible teaches. You are no doubt way, way, way out of line. The bible teaches a flat (but round like a pancake) earth, water below the earth, water above the earth, domes of stars, and astrology galore... It doesn't even get as far as the earth being at the center. The sun crosses the sky and goes back to do it again the next day. Yup! Read it and see! That is the biblical view of the cosmos. Oh, and Heaven is "up there" too, since it clearly isn't down here. And take a look at your view on disease. Don't get me started on the Bible's view of disease and its causes. Demons, curses, sins, and ceremonial uncleanness. Remember that Biblical medication consists almost entirely of olive oil, mud and wine. Robert, deal with it. The Bible does not answer many questions and when you force it to, you lose, and badly.