Comments on Sanford and Carter respond to PS participants

[glipsnort (Steve Schaffner)]

@thoughtful

I meant they might be understanding GE wrong, in regards to selection. It’s new to everyone.

No, GE is not new to everyone. Here are excerpts from an email I sent to Sanford in 2009. (I don’t have the full, original email, just the parts he quoted in responding to me). I have known about Sanford’s model for a long time, and I think the email contents show that I did not dismiss it without thinking about it at some length,

Viewed from a high level, populations crash in your model because of
several features in the model. First, it has a high rate of very
slightly deleterious mutations, ones that have too weak an effect to
be weeded out by selection. Second, the accumulation of these
mutations reduces the absolute fitness of the entire
population. Third, beneficial mutations (and in particular
compensating mutations) are rare enough (and remain rare enough even
as the fitness declines) and of weak enough effect that they do not
counteract the deleterious mutations. As far as I can tell, any model
of evolution that has these features will lead to eventual extinction
– the details of the simulation shouldn’t matter at this
level. (Indeed, Kondrashov pointed out this general problem in 1995; I
wouldn’t be surprised if others have made the same point earlier.)

So there is no question that if these premises of the model are
correct, organisms with modest population sizes (including all
mammals, for example) are doomed, and Darwinian evolution fails as an
explanation for the diversity of life. If one wishes to conclude that
evolution does fail, however, it is necessary to show that all of the
premises are true – not merely that they are possible, but they
reflect the real processes occurring in natural populations. From my
perspective, that means you need to provide empirical evidence to
support each of them, and I don’t think you have done so.

[The following expands on point 2 above. ‘Soft selection’ is selection that affects only relative fitness, not absolute fitness.]

Turning specifcially to issue of soft selection: it matters here
becuase it severs the connection between relative fitness and absolute
population fitness. The essence of soft selection is that the absolute
fitness of the population does not change, regardless of the relative
fitness effects of individual mutations that accumulate in the
population. As Kimura put it, “Therefore, under soft selection, the
average fitness of the population remains the same even if the genetic
constitution of the population changes drastically. This type of
selection does not apply to recessive lethals that unconditionally
kill homozygotes. However, if we consider the fact that weak
competitors could still survive if strong competitors are absent, soft
selection may not be uncommon in nature.” (p. 126, The Neutral Theory
of Evolution).

(An unimportant point: my understnading from reading Wallace is that
he introduced the term “soft selection” in the context of accumulating
deleterious mutations (especially concerns about them raised by Jim
Crow), not in connection with Haldane’s dilemma or the rate of
beneficial substitution. If you have a citation that provides evidence
otherwise, I would be interested in seeing it. The basic model of soft
selection actually goes back at least to Levene in 1953 (predating
Haldane’s work by a few years), when he was considering the
maintenance of varied alleles in a mixed environment. So this is not
a new idea, and it is (contra your suggestion) is a well-defined
concept, and one that is in fact often considered in the context of
deleterious mutations and genetic load. Are there any recent published
discussions of genetic load that do not consider soft selection as a
possibility?)

Regardless of the direct effect on fertility, the use of an
additive model of fitness means that deleterious selection in your
program ultimately ceases to be soft, since accumulating additive
fitness always ends up or below zero, at which point the relative
fitness values no longer matter. In a model of soft selection, the
magnitude of the populations’s fitness makes no difference at all;
only the relative values of individuals have an effect. In your
program, that is not the case. So in practice, your program does not
seem to model long-term soft selection.

(As an aside, I’m afraid I don’t understand your comments about having
tested a multiplicative model of fitness. You say that in such a
model, as the mean fitness falls, you see increasing numbers of
individuals inherit a set of mutations that give a fitness less than
or equal to zero. Under a multiplicative model, the fitness is given
by f = (1-s1) * (1-s2) * (1-s3) *…, where s1, s2, s3… are the
selection coefficients for the different mutations. If the various s
values are less than 1.0 (as they must be if the mutations have been
inherited), then f must always be greater than 0. I don’t see how you
can have a multiplicative model with the reported behavior. Perhaps
you have a noise term that is still additive?)

The real question is whether or not soft selection is actually
important and needs to be modeled. As you say, soft selection is a
mental construct – but so is hard selection. You dismiss it as a real
phenonenon, but do you have any evidence to support your point here?
Your populations crash because of very slightly deleterious mutations,
and as far as I know, virtually nothing is known about what kind of
fitness effects these mutations have. In general, there has been very
little empirical work distinguishing soft from hard selection (or
equivalently, quantifying the difference between absolute and relative
fitness). The only recent study I know of to attempt it looked only at
plant defense traits in A. thaliana (Kelley et al, Evolutionary
Ecology Research, 2005, 7: 287–302), and they found soft selection
effects to be more powerful than hard effects. So I do not see
good empirical grounds for rejecting an important role for soft
selection.

This isn’t to suggest that all selection is soft, or that many
mutations don’t have real effects on the population fitness – but
there are good theoretical and empirical reasons to think that the net
effect of many deleterious mutations is smaller when they are fixed in
the population than their relative fitness would suggest. (Not that we
actually know what the distribution of relative fitnesses looks like,
either. You can pick a functional form for that distribution for the
purpose of doing a simulation, but it based on no real experimental
evidence. Are deleterious mutations really so highly weighted toward
very slight effects? There are just no data available to decide.

If much selection actualy is soft, then humans (and other mammals)
could have in their genome millions of deleterious mutations already,
the result of hundreds of millions of years of evolution; this is the
standard evolutionary model.

These mutations would have accumulated as
population sizes shrank slowly (relaxing selection) and functional
genome sizes grew (increasing the deleterious mutation rate). Indeed,
many functional parts of the genome may never have been optimized at
all: the deleterious “mutations” were there from the start. The
results of this process are organisms that are imperfect compared to a
platonic ideal version of the species, but perfectly functional in
their own right. In your response, you cite systems biology’s
assessment that many organisms are highly optimized to counter this
possibility. I do not find this persuasive, partly because systems
biologists can also cite many features that are suboptimal, but mostly
because no branch of biology has the ability to quantify the overall
optimization of an organism, or to detect tiny individual
imperfections in fitness.

Alternatively, beneficial mutations may be more common and of larger
effect than in your default model. I pointed to one recent example of
a beneficial mutation with a much larger selective advantage than your
model would allow (lactase persistence in human adults). In turn you
suggest that such large effects occur only in response to fatal
environmental conditions, but the example I gave does not fall in that
class. Do you have any empirical evidence that the selective advantage
is restricted to such small values?

Michael Whitlock has a nice discussion of this kind of model in a
paper from 2000 (“Fixation of new alleles and the extinction of small
populations: drift load, beneficial alleles, and sexual selection.”
(Evolution, 54(6), 2000, pp. 1855–1861.)) His model tries to answer
very similar questions to yours. With the choice of parameters that he
thinks is reasonable, he finds that only a few hundred individuals are
needed to prevent genetic decline.

He also discusses many of the same issues that we’re discussing
here. For example, on the subject of soft selection he writes, “We
also have insufficient information about the relationship between the
effects of alleles on relative fitness in segregating populations and
their effects on absolute fitness when fixed. Whitlock and Bourguet
(2000) have shown that for new mutations in Drosophila melanogaster,
there is a positive correlation across alleles between the effects of
alleles on productivity (a combined measure of the fecundity of adults
and the survivorship of offspring) and male mating success. This
productivity score should reflect effects of alleles on mean fitness,
but the effects of male mating success are relative. Without choice,
females will eventually mate with the males available, but given a
choice the males with deleterious alleles have a low probability of
mating. Other studies on the so-called good-genes hypothesis have
confirmed that male mating success correlates with offspring fitness
(e.g., Partridge 1980; Welch et al. 1998; see Andersson 1994).”

His conclusion about his own model strikes me as equally appropriate
to yours: “We should not have great confidence in the quantitative
values of the predictions made in this paper. In addition to the usual
concern that the theoretical model may not include enough relevant
properties of the system (e.g., this model neglects dominance and
interlocus interactions, the Hill-Robertson effect, the effects of
changing environments), the empirical measurements of many of the most
important genetic parameters range from merely controversial to nearly
nonexistent.”

Using this kind of model to explore what factors might be important in
evolution is fine, but I think using them to draw conclusions about
the viability of evolution as a theory is quite premature.