Philosophers and definitions of evolution and allele

One of my Facebook friends posted a link to an article on genetic drift on the Stanford Encyclopedia of Philosophy website [Genetic Drift]. The author is Roberta Millstein and the article is a recent update to an older version that I questioned ten years ago [A philosopher's view of random genetic drift]. I noted on Facebook that this was "Another example of philosophers who don’t understand modern science." By this I meant that the article seemed to ignore the abundant molecular evidence of drift.

That prompted a response from defenders of philosophy and Roberta Millstein joined in. Here's the essence of her defense of philosophy.

The Stanford Encyclopedia of Philosophy is, as the name suggests, about philosophy. Thus, the entry surveys views about drift in philosophy -- starting with the history of drift because some philosophical views about drift, such as my own, take that as their starting point -- which include debates about what drift is and other philosophical topics.

Perhaps if biologists had been crystal clear and consistent about what drift is, there would have been less to write about, but there is good evidence for the claim I make in the entry and elsewhere, that in fact scientists use the term in different ways, some of which I think are unproductive (e.g., describing drift in terms of outcome rather than as causal process).

I'll post a separate article about her views on genetic drift but here I want to address the point that biologists aren't always "crystal clear." It turns out that Millstein doesn't agree with my definition of evolution or my definition of allele so when I try to make the case that fixation of neutral alleles is a clear example of random genetic drift this is challenged by evidence that not all biologists accept my definitions so genetic drift isn't as solidly established as I might think.

The point I'd like to discuss is whether philosophers should critically analyze statements by biologists to see if they make sense or whether they should just report a controversy without questioning the validity or reasonableness of certain statements and definitions.

Scientists don't usually write with the expectation that philosophers will parse their sentences and their meanings. In my opinion, that's not because they don't want to be accurate—it's more likely that they don't think that kind of rigorous accuracy is necessary. And that's because, unlike the laws and theories of physics, biology is inherently messy and for every definition there are exceptions and no model covers every known example.

Also, I think it's true, but unfortunate, that scientists (and philosophers?) often don't think through the implications of what they write and how their words might be interpreted by others. This is related to the interests of particular biologists. As we know, some biologists aren't interested in evolution at the molecular level so they use terms and definitions that don't take molecular data into account. Should philosophers consider this bias? Should philosophers allow for the possibility that biologists don't mean exactly what their words imply?

... it's important to appreciate that natural selection isn't the only process of evolutionary change. Most biologists define evolution as a change in the proportion of alleles (different form of a gene) in a population.

Jerry Coyne in Why Evolution Is True (page 122)Because Roberta Millstein and I don't seem to share the same definitions of 'evolution' and 'allele,' I want to discuss the definitions of each of those words to see if there's a reasonable consensus view.

Evolution

I think evolution is a process that results in heritable changes in a population spread over many generations. This is my attempt to be as precise as possible but it's much simpler to just say that evolution is a change in the frequency of alleles in a population. This is a simple definition that corresponds to the one used by Dan Graur in his book Molecular and Genome Evolution ...

Evolution according to this definition, is the process of change in the genetic makeup of populations, that is, a change in genotype and allele frequencies.

I side with Stephen Jay Gould on this point. Here's what he wrote in "Chance Riches," an important essay published in 1980 and reproduced in the anthology Hen's Teeth and Horse's Toes (p. 335).

Since "change of gene frequencies in populations" is the "official" definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change.

There are other definitions but it's important to emphasize that my preferred definition is a minimal definition that's suitable for describing slight changes at the molecular level. This is made clear in the definition by Douglas Futuyma in his textbook Evolution (2nd ed., p. 2, 2009).

Biological (or organic) evolution is change in the properties of populations of groups of organisms over the course of generations. The development, or ontogeny, of an individual organism is not considered evolution: individual organisms do not evolve. Groups of organisms, which we may call populations, undergo descent with modification ....

The changes in populations that are considered evolutionary are those that are passed via the genetic material from one generation to the next. Over the course of many generations, many changes may accumulate. Thus, biological evolution may be slight or substantial: it embraces everything from slight changes in the proportions of different forms of a gene within a population to the alterations that led from the earliest organisms to corals, grasshoppers, tomatoes, and humans.

Again, for the purposes of this essay, it's important to note that many leading experts agree that changes in gene or allele frequencies count as evolution. So my preferred definition of evolution is not out of line given that we are going to discuss molecular evolution.¹

It's true that many biologists prefer definitions such as "descent with modification" and others will promote definitions that specify natural selection. However, it's not clear whether most of these biologists have thought about molecular evolution and allele frequency changes and whether they have published specific refutations of the changes in allele frequency definition.

But some have. Ernst Mayr, for example, is very clear about his objections to evolution and bean-bag genetics. Here's what he wrote in 1980 in the preface to the Evolutionary Synthesis (p. 12).

It is simply not true that evolution can be explained as a change in gene frequencies. Falling victim to their own definition of evolution, the new geneticists failed to explain the very phenomenon that occupied the attention of the most active students of evolution, such as the multiplication of species, the origins of genetic novelties and higher taxa, and the occupation of new adaptive zones. Changes in gene frequency are a by-product of adaptation and of the origin of evolutionary diversity (induced by natural selection) and not the other way around. As necessary as the advances in the understanding of genetics were, they were not sufficient for the synthesis.

Roberta Millstein is correct, there are biologists who reject my preferred definition of evolution and some of these other definitions rule out a large part of molecular evolution. Millstein doesn't give us her preferred definition of evolution and she doesn't discuss whether some definitions are more reasonable than others.

Alleles

Right from the get-go we discover a problem with defining alleles. Note that Graur refers to alleles in his definition and so does Jerry Coyne (see box). Graur doesn't define allele but Coyne says that alleles are "different forms of a gene." Mayr refers to changes in "gene" frequencies. Futuyma doesn't even use the word allele but refers to "different forms of a gene."

We know that Futuyma isn't just being sloppy in his definition of evolution because on page 216 of his textbook he defines an allele as "a particular form of a gene, usually distinguished from other alleles by its effect on the phenotype." This, however, IS sloppy because it rules out the existence of alleles in regulatory sequences as well as alleles in other functional regions of the genome such as origins of replication and centromeres. It certainly rules out the existence of alleles in non-functional regions of the genome and that's a serious problem.

All evolutionary change initiates as a transient phase of genetic polymorphism, during which mutant alleles navigate the rough sea of random genetic drift.

Michael Lynch in Evolutionary Cell Biology (p. 91)Dan Graur has apparently thought about this problem because on page 35 in his book he defines an allele as "The chromosomal or genomic location of a gene or any other genetic element is called a locus (plural: loci), and alternative DNA sequences at a locus are called alleles." His definition is not confined to genes but it's not clear whether his use of "other genetic element" is restrictive or not.

My preferred definition of an allele is the one we worked out on Wikipedia [Allele].

An allele is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule.

This covers all variants at all loci and it includes things like single nucleotide polymorphisms (SNPs) in junk DNA. It's common in the scientific literature to refer to such variants as alleles even though many of the formal definitions of alleles are more restrictive. I've not seen very many biologists, including Futuyma, argue against calling these alleles even if their formal definition excludes them.

But you can always find somebody who does make such a claim. In this case, it's the cantankerous Ersnt Mayr who writes the following in One Long Argument (p. 152).

The neutralists are reductionists, and for them the gene—more precisely the base pair—is the target of selection. Hence, any fixation of a "neutral" base pair is a case of neutral evolution. For the Darwinian evolutionists, the individual as a whole is the target of selection, and evolution takes place only if the properties of the individual change. A replacement of neutral genes is considered merely evolutionary noise and irrelevant for phenotypic evolution.

Roberta Millstein objected to my definition of allele by pointing out that "Alleles are usually described with respect to functional sequences of DNA." If this is true, then there can't be allele frequency changes in junk DNA and that rules out most of what I think of as evolution in mammalian genomes. It explains why she doesn't think that the documented changes in non-functional DNA represent solid evidence for random genetic drift.

She doesn't give us her definition of allele in the article but it's clear that she isn't comfortable with the definition that I prefer. For example, in her brief discussion of molecular evolution she prefers the term "neutral mutants" rather than neutral alleles. This is another situation where a philosopher could make an important contribution to educating other philosophers by coming to grips with the definition of allele and taking a stance on which definitions were reasonable. That would require a discussion about whether biologists like Futuyma were just being sloppy in their definition or whether they really meant to rule out most of variants in mammalian genomes.

So, when biologists restrict their definition of evolution to changes in "gene" frequency rather than "allele" frequency, are they being rigorous or sloppy? Are they using the word "gene" in the Mendelian sense, as Dawkins does, or are they using the molecular definition of "gene"?

How should philosophers (and other scientists) interpret Futuyma when he says that evolution covers "slight changes in the proportions of different forms of a gene within a population." Roberta Millstein seems to have decided that there isn't much of a difference between changes in gene frequencies and changes in allele frequencies because in her 2007 paper with Robert Skipper she writes,

... population geneticists define "evolution" as change in gene frequencies, or more strictly, any change in the frequency of alleles within a population from one generation to the next.

What's the best way to define "allele"? It seems obvious to me that the word can be used to distinguish variants within a gene that cause phenotypic change. Everybody can agree to that. What about variants within a protein-coding gene that alter a codon but don't change an amino acid and have no detectable effect on the phenotype? Are they alleles?

What about variants in regulatory sequences lying outside of the molecular gene? Such variants can have profound phenotypic effects and they are often referred to as alleles.

What about variants at the origin of replication in the E. coli genome? Such variants can have phenotypic consequences, such as affecting the growth rate.

What about variants within the intron sequences of eukaryotic protein-coding genes? Most of them have no effect on the protein encoded by the gene and that's why we think that most intron sequences are junk. Do those variants always count as alleles? Some of those variants create alternate splice sites and some of those have serious phenotypic consequences as in genetic diseases. Are those variants alleles but not the neutral ones?

If the typical variants in junk DNA aren't alleles then we will have to refer to changes in variant frequency that just happen to correspond to the predictions of population genetics. Does that mean that this isn't evolution? [Evolution explains the differences between the human and chimpanzee genomes]

I don't think philosophers (or scientists) can ignore these questions and just rely on a sloppy definition of "allele" without thinking critically about what that sloppy definition really means. I don't excuse scientists for being sloppy about their definitions but this is clearly the baliwick of philosophers so they can't be excused as easily. If you are a philosopher and you are going to write about random genetic drift, then you better let us know which cases of allele frequency change count as drift and which ones don't even count as evolution.

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1. There are many biologists who aren't interested in evolution at the molecular level so they use other definitions. Since they aren't interested in molecular evolution, they don't feel the need to incorporate it into their definition of evolution; however, they usually don't rule out the minimal definition. On the other hand, there are some biologists, such as Richard Dawkins and Ernst Mayr, who are on record questioning whether all allele frequency changes really count as evolution. I'm ignoring them because that stance is not defensible.