From Doodle Dogs to COVID: On the Meaning of Wild Type

Zeke, shown here retrieving a stick from the surf at Lambert’s Cove, Martha’s Vineyard, is an aussiedoodle – a cross between an Australian shepherd and a poodle. I did an informal survey there over the course of a week, and estimated that approximately 70 percent of the dogs on the beach harbored poodle genes.

Diverse doodles share the trademark tight curly fur, but vary in size, color, head shape, and behavioral and other traits. Several websites list 50+ variations on the poodle hybrid theme, including the bassetoodle, bernedoodle, chipoo, doxiepoo, Irish doodle, poochon, rottle, and shihpoo.

Why poodles? The breed evokes such effusive descriptions as “confident yet affectionate, but also active and deceivingly athletic. What’s not to like about the dignified and elegant Poodle?” The mixes are deemed highly intelligent, although I can’t imagine any of my cats chasing a stick, let alone retrieving it.

Perhaps I was witnessing a biased sampling, and the doodles simply have a combination of gene variants that somehow makes them love running in the sand. I watched, transfixed, as a goldendoodle followed a seabird far out into the surf, upsetting the human observers and revealing a superior avian intelligence.

Still, seeing the apparent influx of poodle genes into canine genomes on the beach brought me back to my graduate school days. That was just before the very first doodles appeared – the labradoodle, bred in Australia in the early 1980s. My observations inspired me to start thinking about the classic genetic term wild type.

Evolving Meanings of Wild Type

In my days as a geneticist, I came to know the traits of fruit flies quite well. “Wild type” back then referred to the most common phenotype – trait – in a population.

Wild type fruit flies have characteristic brick-red eyes. Variations weren’t recognized until a lone white-eyed fly turned up In 1910 in the famed lab of Thomas Hunt Morgan at Columbia University. Discovery of white-eyed flies led to discovery of sex chromosomes. The trait of eye color is carried on the X chromosome (a male fly has one X and no Y; a female has two X’s).

Soon other eye color variants were discovered. The multi-faceted fruit fly eyes also may be sepia, vermilion, cinnabar, garnet, scarlet, or other hues that sound like mixes of paint colors at a hardware store.

Somehow, wild type came to be considered not only the most common phenotype, but because of that prevalence, synonymous with “normal.” I think that is more a tendency of humans to classify organisms, including ourselves, by superficial traits; “normal” is a subjective term.

The opposite of normal is mutant. As far as I know flies do not mind being called a mutant, but a human with an unusual trait – an extra finger, a unibrow, a rare blood type – might. So “variant” is a less judgmental, more acceptable term.

Now COVID has changed the meaning of wild type.

I’ve heard politicians and physicians, some presented as experts, equate wild type to “natural.” I suspect some biology teachers and biologists cringed a little, as I did. Back at the beginning of the pandemic, the equivalency of “wild type” and “natural” might have referred to the idea that SARS-CoV-2 escaped from a lab in China, which would presumably have been an unnatural event.

(ASIDE: “Gain-of-function” is another term borrowed from genetics, to support the pandemic origin scenario of a laboratory escapee. The classical definition is that removing a gain-of-function mutation doesn’t alter the phenotype, whereas removing a loss-of-function mutation does. But the most egregious and persistent borrowing and changing of scientific terminology is “organic.” It means “carbon-containing.”)

Some definitions of wild type combine “natural” and “normal.” The National Cancer Institute, for example, defines wild type as “a gene when it is found in its natural, non-mutated (unchanged) form.”

I like the Merriam-Webster dictionary definition, which combines ideas old and new: “a phenotype, genotype, or gene that predominates in a natural population of organisms or strain of organisms in contrast to that of natural or laboratory mutant forms.”

The National Institutes of Health definition drills down to the viral viewpoint,“The naturally occurring, non-mutated strain of a virus,” while the free medical dictionary calls a wild type virus a “street virus.”

Google’s definition is the most granular (another term borrowed from biology; granulocytes): “a strain, gene, or characteristic, which prevails among individuals in natural conditions, as distinct from an atypical mutant type.” That explanation reveals the fluidity of the term: the most common expression of a trait in a population can change.

Wikipedia’s definition is the best, leading back to the doodles on the beach:

“most or all gene loci exist in a variety of allelic forms, which vary in frequency throughout the geographic range of a species, and that a uniform wild type does not exist. In general, however, the most prevalent allele – i.e., the one with the highest gene frequency – is the one deemed wild type.”

With poodle genes infiltrating the genomes of dozens of other breeds, it seems that poodles in some form are on the way towards becoming wild type. In contrast, wild type for SARS-CoV-2, the virus behind COVID, has become a series of waves, the newest genotype (including dozens of mutations) overtaking the forerunner in a matter of weeks, sweeping the globe in unending undulations.

The Changeling SARS-CoV-2

The novel coronavirus began to relentlessly reinvent itself in March 2020 with the tiny but powerful D614G mutation that accelerated spread. Single-base mutations continued to appear and accrue into ever more complex variants, which begat subvariants and variants of the subvariants. So much change has happened that “wild type” seems to be an ephemeral state, perhaps even an obsolete term, unable to capture the changeling virus, an entity so simple that it isn’t even considered alive.

And so “wild type” in the COVID world no longer refers to “normal” or “natural,” but simply, and relatively, to which variant prevails at any given moment. That’s what we see weekly as the genetic changes in the virus pop up, accrue, and recombine.

Evolution of the virus elegantly displays the trio of forces that define microevolutionary change: mutation, natural selection, and recombination.

Mutations arise, like typos, as genetic material (DNA or RNA) copies itself. Selection enables some genetic variants to persist as others wane. Recombination of existing traits of a species leads to new mixes, like the doodles.

SARS-CoV-2 does all three: it changes, persists or not, and recombines, swapping swaths of mutations. That’s why we helpless hosts can’t keep up.

CODA

What I love about genetics is that the rules apply to all species, from adorable doodles to villainous viruses. What I also love about science in general, and genetics in particular, is that the terms are flexible, their meanings changing as our understanding of the natural world grows.

And so the definition of wild type has gone from “most common” to “normal” to “natural” and back full circle to “most common.” The changing descriptors are perhaps a metaphor for science itself, for science isn’t a static list of rules, it isn’t the final word, and there’s no such thing as scientific “proof.” We’re always learning more, asking new questions about the natural world, and amending what we thought we knew.