Russ Hodge1*, Pablo Mier Munoz2, and Miguel Andrade2
- Max Delbrück Center for Molecular Medicine of the Helmholtz Association, 13125 Berlin, Germany
- Faculty of Biology and Center for Computational Sciences in Mainz (CSM), Johannes Gutenberg University Mainz, 55128 Mainz, Germany
* Corresponding author: Russ Hodge, firstname.lastname@example.org
Conflict of interests: This project has received no funding from the pizza industry or its competitors, and there are no other conflicts of interest.
Pizza has long held a stigma in biological research that dates back to Linneaus, who was intimately familiar with its properties as an aphrodisiac but failed to recognize it as a living organism. As a result, species of pizza found no place within his elaborate system of classification, and have consequently been entirely omitted in the clade systems developed by evolutionary biologists. Add to this the nigh impossibility of maintaining pizza in laboratories, from which it tends to spontaneously disappear through mechanisms that are poorly understood, and the result is that pizza has been forgotten in the deep freeze as the life sciences have moved forward in great strides. The issue is complicated by the fact that from one point of view, a pizza resembles a single cell, with a crusty membrane and a diversity of clearly defined organelles, while from another perspective it shares properties of highly developed multicellular organisms, and from a third it seems to resemble an ecosphere containing a diverse range of symbiotic subspecies. Finally, the fact that pizzas never evolved a skeletal or exoskeletal system has led to a paucity of fossil remains which otherwise would surely have generated interest among the paleobiology community and provided insights into the descent of modern species.
The synthesis of Darwin’s theory of evolution with findings from genetics has led to modern, computational approaches based on comparisons of modern organisms, whose features permit a reconstruction of the characteristics of ancestral species. Here we apply the basic principle of “common descent” in a first attempt to construct an evolutionary tree of pizza. Modern varieties have clearly undergone human domestication and selection, and a small number of mutant strains have spontaneously appeared in recent years. While these factors confound the picture to some degree, the method does, in fact, permit a means of resolving questions about pizza biology that have long resisted analysis.
The resulting diagram introduces considerable clarity into the path by which current species of pizza arose from a single common ancestor, through stages that became the founders of major branches, and finally to modern forms. It permits us to hypothesize the existence of ancestral forms that have homologs in the varieties that exist today. Finally, it provides insights into fundamental biological processes that are unique to pizza, supporting a claim that these species represent a fourth domain of life which is distinct from archaea, bacteria, and eukarya, but which has clearly interacted with them in ways that have shaped its evolution.
We find evidence that pizza has managed to co-opt fundamental biological processes from the other domains of life and mix them in a way that hints at hitherto unexplored evolutionary mechanisms. Pizza appears to have snatched genes from various sources on its way to becoming an independent organism, then undergone a phase in which it became wholly dependent on human domestication, leading to a simplification of its biology. Our study suggests that the appearance of pizza in complex ecospheres containing other life forms influences them on several levels – from the neurological to the behavioral to the social, altering patterns of predation and other types of interspecies interactions.
METHODS AND RESULTS
We visited approximately 100 different Italian restaurants in a sample of no less than five European countries over a period of 4 years (extrapolated from social media statistics of the authors: FourSquareTM, GoogleTM Location History, etc.) to gather the names and ingredients present in a total of 58 different pizzas (Supp.File1). While we did not taste them all, we can attest that none are venomous and their organoleptic qualities can therefore be successfully transmitted mouth-to-mouth to the next generation of diners.
The ingredients were clustered in 9 groups according to their origin and use in cuisine (Table 1). Tomato sauce and mozzarella form their own groups, as they are not considered ingredients but inherent components of the pizza (Combet et al., 2014). The pineapple was set apart in a group by itself as an obvious aberration, due to the fact that it is universally recognized as a dysfunctional mutation that arises from a hybridization event (somewhat like the mule) and cannot produce viable offspring.
Table 1. Ingredients considered per group.
||Cream, truffle cream
||Gorgonzola, parmesan, ricotta cheese, fontina cheese, scamorza, stracchino, asiago
|Meat / eggs
||Beef, salami, raw ham, ham, bacon, sausage, bresaola, egg
|Fish / seafood
||Tuna, anchovies, seafood
|Condiments / herbs
||Pepper/green peppers, oregano, rosemary, parsley, genoese pesto, garlic, olive oil
||Artichoke, zucchini, asparagus, spinach, peas, eggplant, assorted vegetables, sliced tomato, courgette flower, onions, olives, mushrooms, rucola/rocket, potato, french fries, corn, polenta, radicchio
It is notable that not a single pizza contains more than three ingredients from the same group, which hints that this might lead to some sort of synthetic lethality, or a genetic event along the lines of the acquisition of excess chromosomes.
The pizzas were scored by counting the number of ingredients they contained per group. Exceptions are the tomato sauce and the mozzarella, which were counted as three ingredients each due to their importance in the general composition of the pizza. The data was analyzed using the R programming language and Rstudio, to cluster the pizzas based on their ingredients. The result was plotted in a clustered heatmap using the pheatmap R package (Kolde, 2015).
Tomato sauce and mozzarella are the key components in the pizza and serve as classifiers (Figure 1). Ingredients from the meat/eggs and/or vegetables groups are often used as the toppings to go together with the main components of the pizzas.
Here we present the first rigorous attempt to sort out major questions regarding the origins and evolution of pizza, a domain of life that has been shamefully neglected by science even as it has been shamelessly ingested by scientists. It is difficult to determine the reasons for this neglect. One cannot definitively rule out some sort of large-scale conspiracy on the part of lobbyists for the international grocery industry, possibly in cahoots with the Mafia. Recognizing pizza as a life form would require the development of an entire apparatus of regulatory measures with regard to society’s wholly utilitarian approach to its handling and use – not to mention a plethora of ethical issues it might raise. Pizza is treated as an inanimate object with no consideration at all for the fact that it might have some sort of limited awareness and experience feelings of distress or pain.
It is important to note that in modern times, pizza species have become entirely dependent on human cultivation, like many plants, domesticated animals, and model organisms in laboratories and are no longer competent for survival in the wild. The biology of pizzas has become simplified through this dependency; modern forms have lost genes that were originally crucial to its survival. Thus their evolutionary path resembles that of pathogens and viruses. Under normal processes of natural selection, organisms that are tastiest to their predators are eaten more and are subject to intense negative selection. This would also be the case for pizza, particularly since it has no means of escape from its human predators. But domestication has reversed this trend, positively selecting for the forms that are most likely to be eaten.
Our observations of pizza in situ suggest that its basic biology draws on unique features which are hard to reconcile with those of tired old traditional models that people have studied to death and are now thoroughly bored with. Pizza is a fixture of worldwide ecosystems and global food chains, nourishing species as diverse as college students, cops, bowling teams, other categories of humans, dogs, cats, hamsters, pigs, rats, cockroaches, crocodiles, fish, etc. Old crusts that have fallen down cracks in sofas provide a rich environment for microbial life, including bacteria such as legionella, Yersinia pestis and Mycobacterium leprae which might otherwise become extinct. This gives it a central role in global biodiversity; one might even regard it as the glue that holds everything together. But this is somewhat speculative.
Technical obstacles have made it difficult to maintain pizza in laboratory cultures, resulting in a dearth of knowledge – practically a black hole of knowledge – surrounding it. This is alarming in light of the numerous epidemiological studies tying pizza to serious health problems including obesity, addiction, attention deficit disorders, frostbite, burnt tongues, and deaths related to placing aluminum foil in microwave ovens. Excessive consumption retards human cognitive development, pushing adolescence far into the college years, which can only be reversed by adding vegetables to the diet. Pizza has led to a major reduction of human motility, allowing people to sit on the couch as it is delivered to their homes. Soon they may not even need to get up to answer the door, now that Amazon has begun to deliver food by drone: a step in the company’s plan to achieve world domination.
We applied well-established methods of phylogenetic analysis to the features of pizza (namely, the ingredients found in 58 extant species) to derive the first systematic evolutionary account of its descent from an ancestral form. The results point firmly to a last common ancestor, providing insights into fundamental aspects of its biochemistry, development, and the selective forces that have shaped its evolution into diverse types. A key observation is that the ancestral pizza exhibited very little elaboration of specialized structures. It consisted of only three tissues: dough, tomato sauce, and mozzarella. Each exhibits a high degree of molecular complexity, but very stable biophysical properties that are crucial to maintaining the integrity of the organism over time.
- The pizza lifecycle
The pizza lifecycle is marked by the three phases of embryogenesis, maturation, and decline. Entry into a phase is determined by environmental factors: embryogenesis takes place at room temperature; maturation begins when the temperature dramatically rises to about 220 degrees Celsius and usually lasts 10-12 minutes. Returning to normal room temperature introduces a brief period of homeostasis after which pizza enters the phase of decline.
Laboratory experiments have shown that pizzas which have completed embryogenesis can be preserved through cryopreservation, which induces a state of dormancy or hibernation. They can be maintained this way for a year or two without any apparent damage. The decline phase can be prolonged by a day or two through cooling, after which a brief exposure to heat is used to revive the pizza. This may cause it to repeat the last stages of maturation and then enters the decline phase, which is now accelerated.
- Tissue structure through the lifecycle
Dough begins as an elastic substance under room temperature, which is characteristic of the environment of embryogenesis; in the heating phase it becomes crisp and remains that way as it cools, matures, and approaches death. The sauce begins as a thick fluid which crystallizes somewhat at the pinnacle of the heating phase, remaining somewhat gummy through the first phases of cooling, then hardens until it is nearly all crystallized at the end of cooling. Mozzarella begins as a rubbery substance, melts into a liquid under heat, and only hardens after an extended period of cooling over time. These transformations of the three tissues do not alter the basic structural integrity of the whole, unless the pizza is subjected to unusual forces such as those it would encounter when flung through the air. An embryonic pizza would stretch and fly apart; the hardness of a mature pizza gives it the properties of a Frisbee.
The earliest stage of pizza’s embryonic development bears some similarities to Dictyostelium, an organism that lies at the borderline between unicellular and multicellular life. Dough assembles in an environment containing sufficient concentrations of the necessary chemical and biological ingredients: particles of wheat, water, sugar, and some form of oil. Such environments usually contain abundant populations of yeast cells, which get dragged along as the components are attracted to a central location, probably by sensing chemokine-like molecules that have been secreted by a cook’s hands.
Upon arrival the components merge in a sort of symbiotic collective that draws on the genes of the wheat and yeast to trigger a series of metabolic reactions that derive energy from the sugar and oil. The result is to fuse everything into a pliant, undifferentiated mass of dough. Originally this is a ball-shaped mass with stem-cell like properties that may yield a single pizza or be pinched off to form genetically identical twins.
The ball spreads across a surface to form a flat, circular basal membrane on which new layers will arise. The dough induces the formation of tomato sauce, rapidly followed by a layer of mozzarella. This three-layered structure is highly reminiscent of the tissues that arise in animal gastrulation, except that their cells retain the ball-like shape. This single difference, combined with the fact that embryonic pizza does not have a womb to protect it from dramatic changes in temperature, probably severely restricted the amount that ancient pizzas could vary from the original design. While eventually they developed specialized organelles such as salami and funghi, there was never much variation to serve as the basis for selection. So the type of evolutionary tinkering that occurred in animals and shaped the formation of highly sophisticated organs, such as the brain, never occurred in pizza. The Cambrian explosion went by virtually unnoticed.
Our investigation provides the first account of the evolutionary route by which modern species of pizza diverged from an ancient, ancestral form. We characterize the last common ancestor as sharing the three-layer structure of modern pizzas, which resembles the first stage of animal gastrulation; in contrast to animals, however, pizza got stuck there and never added additional developmental stages. It is interesting to speculate what might have happened if instead of flattening, dough had retained its original, ball-shaped form and built layers of sauce and cheese inside. (Pizza calzone, a modern species, has this structure, but its dough occurs as the final step in embryonic development.) Perhaps this branch of life would have followed an evolutionary path much more like our own, and pizza, rather than humans, would have become the preeminent form of intelligent life in the known universe.
From the point of view of thinkers such as Dawkins, the key value of intelligence is to promote the reproduction of a species’ genes. Pizza found an alternative by entering into a symbiotic or parasitic dependency on humans as a means of promoting its reproduction. That dependency increased over time, ultimately restricting the evolution of pizza to the path that produced the species we know to day.
Preliminary data suggest that it may be possible to push the ancestry of pizza back even farther, to a point at which the ancestral form diverged from other organisms such as crêpes, pancakes and burritos. We are currently pursuing this question in a large international consortium and will publish the results at a later date.
- Combet E., Jarlot A., Aidoo KE., Lean ME. Development of a nutritionally balanced pizza as a functional meal designed to meet published dietary guidelines. Public Health Nutr. 2014 Nov;17(11):2577-86. doi: 10.1017/S1368980013002814.
- Kolde R. (2015). pheatmap: Pretty Heatmaps. R package version 1.0.8. https://CRAN.R-project.org/package=pheatmap.
Supplementary files will be provided by the author upon request