Is the laboratory strain of Heligmosomoides polygyrus a separate species, H. bakeri?
Origin of the lab model – from deer mice in California to lab mice across the world
The laboratory model nematode Heligmosomoides polygyrus, was redesignated from its earlier name, Nematospiroides dubius, in 1991 (Behnke et al., 1991). This parasite has been maintained in laboratory mice (Mus musculus) for many decades although its exact provenance is somewhat clouded. In the US, two separate primary isolates were obtained from Mus musculus in 1939 (Spurlock 1943) and Peromyscus deer mice in 1950 (Ehrenford 1957) both from a location in Davis, California. In the UK, the parasite was first maintained from 1956 at the Wellcome Laboratories; Quinnell et al (1991) stated that the laboratory line maintained at Wellcome is derived from the 1950 Davis isolate, although Behnke 2009 cast some doubt with the comment that this remained “uncertain in the mists of time”.
Durette-Desset et al (1972) suggested two routes by which the parasite would have reached the Americas, in paleolithic times through the then conjoined Behring Strait, or with Mus musculus on transatlantic ships in the last millenium. If the latter is correct, the timeframe is exceptionally short for a new species to emerge. Indeed, these authors refer only to two subspecies, the European H polygyrus bakeri and the American H polygyrus americanus.
Renaming H. polygyrus
In 2006 Cable, Behnke and colleagues proposed reclassifying the laboratory parasite as Heligmosomoides bakeri, with H. polygyrus reserved for parasites in wild European populations of the wood mouse Apodemus sylvaticus. Rick Maizels, James Hewitson and William Gause argued in their 2011 paper that such a renaming was poorly supported and, at best, premature, suggesting that the distinction could more appropriately be made at a subspecies level as H. polygyrus bakeri (laboratory strain) and H. polygyrus polygyrus (wild isolates), corresponding to taxa originally proposed by Durette-Desset. Since then, the majority of authors and publications have used H.polygyrus or H. polygyrus bakeri when describing laboratory studies (the latter often neatly abbreviated to Hpb).
What do the genomes tell us?
More recently, the complete genomes of the laboratory strain (as maintained at the University of Edinburgh) and a wild isolate have been compared (Stevens et al 2023); 3 individuals of the same lab isolate and 2 individuals from wild Apodemus were sequenced to a near-chromosome level (~100 scaffolds for 6 chromosomes), showing a relatively high level of nucleotide divergence (although far less divergent than another species, H. mixtum). Importantly, worms of all sources showed hyper-divergent gene sequences, nearly 50% of which were shared polymorphisms indicating either recent gene flow or remarkable selective pressure within different host species to maintain the same multi-allelic systems over the 1-6 million year timespan since their last common ancestor postulated by the authors.
What’s in a Species?
A key criterion of separating species is that there is no gene flow between them in the wild, either because they are geographically isolated or there are incompatibilities that prevent fertile offspring. It is not sufficient for the organisms in question (here Heligmosomoides) to be found in different host species, as there are abundant examples of parasites with broad host specificity (e.g. Toxoplasma gondii). In one report from South Korea, “H. polygyrus” was found in 42% of Apodemus and 31% of Mus musculus in the same location, offering ample opportunity for hybridization.
Quinnell et al (1991) explored whether the lab and wild-caught isolates were equally infective to lab Mus musculus and wild-caught Apodemus sylvaticus. The results were asymmetric, in that the lab parasites could infect Apodemus (albeit more briefly) suggesting that the two “strains” would be able to cross-fertilise in the wild.
Is the lab strain one from deer mice now adapted to Mus musculus? Very probably !
Studies on the 1950 Peromyscus-derived isolate, maintained in the laboratory for 16 years, found that it had lost infectivity for its original host species, having become adapted to Mus musculus (Forrester 1971). Indeed nematodes of related species show rapid adaptation that is likely to be epigenetic as well as any contribution of genetic selection (Forrester 1971, Dobson 1977, Ferguson 2023).
Why changing the name is not such a great idea
One problem with designating the lab-maintained strain as H. bakeri is creating a species that only exists in the laboratory : no wild member of this “species” has been isolated. Associated with this, it is not known how rapidly the parasite undergoes genetic drift or specialisation in laboratory cultivation, the report of deer mouse-isolated parasites adapting to the lab mouse is indicative of quite rapid change. In the absence of any data from wild-caught “H.bakeri” its designation as a new separate species is unsafe.
There is also the social side of the argument; taxonomic designation has an inevitable subjective component and re-designation (renaming) can quickly fracture the field and the literature. In this very case, few references are made to the older literature of Nematospiroides dubius! Renaming creates a barrier to newcomers and nonspecialists, and a loss of recognition by policy makers and the public, as has been argued when proposals for renaming Anopheles mosquitos were rebuffed, (Harbach 2018) and the replacement name for the dengue/yellow fever mosquito Aedes aegypti was rejected by the community (Polaszek 2006).
References
Behnke, J.M., Keymer, A.E. and Lewis, J.W. (1991). Heligmosomoides polygyrus or Nematospiroides dubius ? Parasitology Today 7: 177-179.
Behnke, J.M., Menge, D.M. and Noyes, H. (2009). Heligmosomoides bakeri: a model for exploring the biology and genetics of resistance to chronic gastrointestinal nematode infections. Parasitology 136: 1565-1580.
Cable, J., Harris, P.D., Lewis, J.W. and Behnke, J.M. (2006). Molecular evidence that Heligmosomoides polygyrus from laboratory mice and wood mice are separate species. Parasitology 133(Pt 1): 111-122.
Dobson, C. and Owen, M.E. (1977). Influence of serial passage on the infectivity and immunogenicity of Nematospiroides dubius in mice. Int J Parasitol 7(6): 463-466. http://www.ncbi.nlm.nih.gov/pubmed/598964
Durette-Desset, M.C., Kinsella, J.M. and Forrester, D.J. (1972). Arguments en faveur de la double origine des Nématodes néarctiques du genre Heligmosomoides Hall, 1916. Ann Parasitol Hum Comp 47(3): 365-382.
Ehrenford, F.A. (1954). The life cycle of Nematospiroides dubius Baylis (Nematoda: Heligmosomidae. J Parasitol 40: 481-482.
Forrester, D.J. (1971). Heligmosomoides polygyrus (=Nematospiroides dubius) from wild rodents of northern California: natural infections, host specificity, and strain characteristics. J Parasitol 57(3): 498-503. https://www.ncbi.nlm.nih.gov/pubmed/5090957
Harbach, R.E. (2018). An Anopheles by Any Other Name …? J Med Entomol 55(5): 1069-1070.
Kim, D.G., Park, J.H., Kim, J.L., Jung, B.K., Jeon, S.J., Lim, H., Lee, M.Y., Shin, E.H., Klein, T.A., Kim, H.C., Chong, S.T., Song, J.W., Baek, L.J. and Chai, J.Y. (2015). Intestinal nematodes from small mammals captured near the demilitarized zone, Gyeonggi province, Republic of Korea. Korean J Parasitol 53(1): 135-139.
Maizels, R.M., Hewitson, J.P. and Gause, W.C. (2011). Heligmosomoides polygyrus: one species still. Trends Parasitol 27(3): 100-101. S1471-4922(10)00233-3 [pii]
Quinnell, R.J., Behnke, J.M. and Keymer, A.E. (1991). Host specificity of and cross-immunity between two strains of Heligmosomoides polygyrus. Parasitology 102 Pt 3: 419-427.
Spurlock, G.M. (1943). Observations on host-parasite relations between laboratory mice and Nematospiroides dubius Baylis. J Parasitol 29: 303-311. https://www.jstor.org/stable/3272606
Stevens, L., Martinez-Ugalde, I., King, E., Wagah, M., Absolon, D., Bancroft, R., Gonzalez de la Rosa, P., Hall, J.L., Kieninger, M., Kloch, A., Pelan, S., Robertson, E., Pedersen, A.B., Abreu-Goodger, C., Buck, A.H. and Blaxter, M. (2023). Ancient diversity in host-parasite interaction genes in a model parasitic nematode. Nat Commun 14(1): 7776.. https://www.ncbi.nlm.nih.gov/pubmed/38012132