Claim № 4.01  · Pillar 4 · Case file

“Random mutation plus natural selection produces new genetic information.”

Disciplines: Genetics · Biochemistry · Information theory
Status: draft · pending expert review
UnderExaminationTwo claims · two grades

§1 The claim, as taught

Mutations are the original source of all genetic variation. Gene duplication followed by mutation can give rise to genes with new functions. Over vast spans of time, the accumulation of such changes, filtered by natural selection, accounts for the diversity of life.Representative summary of introductory-text treatments (e.g. Campbell Biology, chapters on mutation and genome evolution). PLACEHOLDER: to be replaced with exact quotations and page numbers.

§2 The strongest evidence offered

These are the examples most often cited. We present each one fairly and say what it actually shows.

Observed

Lenski's E. coli: citrate use

In the Long-Term Evolution Experiment, running since 1988, one population gained the ability to use citrate in the presence of oxygen after about 31,500 generations. The key step was a duplication that placed the existing citT transporter gene under a promoter active with oxygen.
Blount et al., PNAS 105 (2008); Blount et al., Nature 489 (2012)
Observed

Nylon-digesting bacteria

Bacteria were found digesting byproducts of nylon manufacture, a substance that only appeared in the 20th century. Structural work showed that the enzyme (NylB) shares the fold of an existing enzyme family, and that a few substitutions raised its activity.
Negoro et al., J. Biol. Chem. 280 (2005); cf. Ohno, PNAS 81 (1984)
Inferred

Gene families from duplication

Genomes contain families of similar genes, such as the globins and opsins. Researchers infer that these arose by duplication followed by divergence. The pattern is observed. The history is reconstructed.
Ohno, Evolution by Gene Duplication (Springer, 1970)
Inferred

Function in random sequences

An ATP-binding activity was found at a frequency of roughly 1 in 1011 in a library of random protein sequences. This is cited to show that functional sequences may be less rare than critics claim.
Keefe & Szostak, Nature 410 (2001)

§3 The grade: two claims hiding in one

The textbook statement combines a modest claim with a sweeping one. Graded separately, they look very different. Hover or tap a rung to see why it got its score. How the grading works →

Mutations modify, tune or break existing genes

BStrongly supported
Observation
///
Directly sequenced in lab populations (LTEE, yeast, viruses).
Hypothesis
///
Precise and testable: a specific mutation leads to a specific effect.
Prediction
//
Resistance and adaptation are routinely predicted and then seen.
Experiment
///
Controlled experiments with frozen ancestors to compare against.
Replication
///
Reproduced across many labs and organisms.
Falsifiability
//
Alternatives such as pre-existing variation are tested and often ruled out.
Method score 16/18

Mutations originate new protein folds and multi-part systems

DExtrapolation
Observation
/
No new fold has been observed arising de novo. Gene families are inferred.
Hypothesis
/
Usually stated as a general possibility, not as a specific pathway.
Prediction
/
Few risky predictions. Failures tend to be absorbed by adding time.
Experiment
/
Lab work shows modification, not new folds (cf. Axe 2004; Keefe & Szostak 2001).
Replication
/
There is nothing positive to replicate yet.
Falsifiability
—
It is unclear what result would count against it. Design is excluded by assumption.
Method score 5/18
ADemonstratedBStrongly supportedCPlausible inferenceDExtrapolationEAssumption

§4 What it would take

Here is what would move the claim up a grade. These are not impossible demands. They are the observations the claim itself implies.

  • A new fold, observedShow a protein fold with no detectable similarity to existing folds arising by undirected mutation in a laboratory population.
  • A multi-part system, observedShow a new function that needs several new, cooperating parts appearing step by step, where each step is selected for.
  • A rate that fits the clockShow that measured mutation rates, population sizes and waiting times can produce the required innovations in the time available.

§5 Another reading of the same data

Across decades of experimental evolution, most adaptive mutations damage or remove an existing function, or adjust its regulation. Michael Behe surveyed the experimental literature and called this “the first rule of adaptive evolution”: break or blunt any gene whose loss would increase the number of offspring. The citrate result fits the pattern. A transporter the cell already had was switched on under new conditions.

Douglas Axe's mutagenesis experiments estimated that about 1 in 1077 sequences forms a working enzyme domain of around 150 residues. That figure is disputed, and other estimates are far more generous (see Claim № 4.03). But if it is anywhere close, a random search cannot find new folds in the time and population sizes available.

Read through a design lens, living things look as if they were built with a rich initial store of information and the capacity to adapt: to adjust, switch on, or give up existing functions as conditions change. The observations fit that reading at least as well as they fit the textbook one.

§6 Reasoning check

The grade weighs the evidence. This check looks at the reasoning: the step from the evidence to the conclusion. The same tests are applied to both readings. How the reasoning check works →

In the claim as taught
  • Clear case

    “New genetic information” covers two things: a new use for an existing gene, which has been observed (citrate), and new genes and folds, which have not. Evidence for the first is counted as evidence for the second.

  • Clear case

    “Over vast spans of time … accounts for the diversity of life” extends observed tuning and breaking of genes to the origin of every biological novelty, without showing that the process scales.

  • Possible
    In the evidence: Lenski's E. coli: citrate use

    Often reported as “a new function evolved.” What was observed was an existing transporter expressed under new conditions. Both descriptions are accurate; only the second says what kind of novelty it was.

In the other reading
  • Possible

    Behe's “first rule” generalises from laboratory and short-term studies, which favour quick gains by losing function. Whether the rule holds over longer times and larger populations is an open question, and should be tested rather than assumed.

§7 Questions to ponder

  • Is gaining a new use for an existing gene the same as gaining a new gene?
  • If the citrate trait took about 31,500 generations in a population of trillions, what does that suggest about the rate of more complex innovations?
  • The 1 in 1011 and 1 in 1077 estimates measured different things. What would a fair comparison require?

§8 Sources

Supporting the mainstream claim
  1. Blount ZD, Borland CZ, Lenski RE. “Historical contingency and the evolution of a key innovation in an experimental population of Escherichia coli.” PNAS 105:7899–7906 (2008).B
  2. Blount ZD, Barrick JE, Davidson CJ, Lenski RE. “Genomic analysis of a key innovation in an experimental Escherichia coli population.” Nature 489:513–518 (2012).B
  3. Keefe AD, Szostak JW. “Functional proteins from a random-sequence library.” Nature 410:715–718 (2001).C
  4. Negoro S, et al. “X-ray crystallographic analysis of 6-aminohexanoate-dimer hydrolase.” J. Biol. Chem. 280:39644–39652 (2005).B
  5. Ohno S. Evolution by Gene Duplication. Springer (1970).C
Critical & alternative perspectives
  1. Behe MJ. “Experimental evolution, loss-of-function mutations, and ‘the first rule of adaptive evolution’.” Quarterly Review of Biology 85:419–445 (2010).B
  2. Axe DD. “Estimating the prevalence of protein sequences adopting functional enzyme folds.” J. Mol. Biol. 341:1295–1315 (2004).C
  3. Behe MJ. Darwin Devolves. HarperOne (2019).C
  4. Sanford JC. Genetic Entropy. FMS Publications, 4th ed. (2014).C

Source grades are provisional. In production each links to a full published evaluation that readers can challenge.

§9 Your notes

Fig. 4.01  Interactive · Mutation Lab

Mutate a working “gene”

A sentence stands in for a gene, with words as its functional parts. Each mutation changes one random letter. Turn on selection to keep only mutations that leave every word readable. See whether selection preserves meaning or builds new meaning.

GOD MADE EACH KIND TO FILL THE EARTH AND THE SEA
Lab ledger
Mutations attempted0
Words broken0
Removed by selection0
New real words formed0

This is an analogy, and analogies have limits. Real genes have some redundancy, and real selection acts on whole organisms. Even so, the lab shows a real distinction: keeping function is different from creating it. For real codons and amino acids, try the DNA explorer in the Probability Lab.