Reviewer 1: W. Ford Doolittle (Dalhousie University, Halifax, Canada)
This paper is both fun and serious. There is a need to develop new ways of conceptualizing gene and genome evolution, globally, and borrowing from economics is potentially fruitful. I also agree with the authors' characterization of the state of play, that as a community we are now "straddling the middle ground - there is a great Tree of Life (sensu Darwin, Lamarck, etc) but it has annotations and complications superimposed upon its great frame, caused by interspecies gene transfer."
As well, I'd agree that "the Tree of Life hypothesis is almost unique in having been modified so extensively from its original description, in order to avoid its rejection". But I do wonder at the third author's acceptance of such a malleable notion, in the context of the 2007 paper [38] in which he and I were rather more specific about what we called the "Tree of Life hypothesis". We described it there as the notion that the tree-like patterns of "groups subordinate to groups" already recognized as natural before 1859 could be explained by (were caused by) an underlying tree-like pattern of successive lineage branchings. This is a testable casual hypothesis not least because there are alternatives, as presented by Peter Gogarten and colleagues elsewhere in this issue. And, we claimed, it was a cornerstone of Darwin's theory.
The chameleon-like Tree of Life hypothesis that seems to be referred to here (as a foil to the authors' Public Goods Hypothesis) must be a weaker conjecture, maybe something so vague as "There is a Tree of Life", or so vacuous as "Application of tree-building algorithms will build a tree", or (best case scenario) "There is a Tree of Cell Divisions that we can know, even if it is way less predictive than we had hoped". It is perhaps something like this, more casual than causal, that most tree-builders do have in mind and is thus referred to in this paper.
Author's response: We have been more explicit about Tree of Life hypotheses and indeed we are not talking about the casual ToL nor are we talking about the Public Goods hypothesis as something casual - we describe it as the basic model for producing the variation in heritable features that we see in evolving entities. We have included clearer statements on the ToL hypothesis such as "To put it another way, all formulations of the Tree of Life hypothesis have at their core the basic tenet that the pattern of diversity that we see on the planet is caused by a tree-like evolutionary process and the differences in these formulations is to be found in how much they allow deviation from this central idea".
I would quibble with the authors' assertion that the existence of CRISPRs and restriction-modification systems "testifies to the evolutionary success of (and obvious need for) mechanisms that protect against the (passive or aggressive) acquisition of genes". CRISPRs do seem to have evolved as protection against phages and maybe burdensome plasmids but it seem most unlikely that there is serious selection against importation of foreign genes per se, and restriction-modification systems may be selfish in nature [83].
Author's response: We agree with the comment on R-M systems being selfish in nature, but our comment on CRISPRs and R-M systems is simply the observation that these are genes that have evolved to counter the dangers of parasite DNA being incorporated into the host genome or cell. They can successfully prevent this from happening. This is in contrast to being eaten by parasites (antibiotic genes, for instance, function to resist being engulfed or outcompeted). Therefore, our difference in opinion might come down to the interpretation of the word "serious" in the phrase "serious selection against importation of foreign genes".
I also think there is much more that can be done with such public goods thinking in terms of what's in it for the genes themselves. If a particular sort of function is dispensable (what Lawrence and Roth [78] called a weakly selected function), and if the function can be performed by many different genes (and maybe even many different families of genes), there will be competition among such genes. How might one win out over others? Possibilities would be to have fewer prior co-evolved attachments (as in the "complexity hypothesis" of Jain et al. [75]) Another would to be not to use too many generally rare codons or expensive amino acids. A third might be to be short. It may be that such selected properties of public goods genes determine some of the global properties of bacteria and their genomes that we currently think of us selected at the level of cells and genomes, for instance the lesser level of connectivity (number of protein-protein interactions) of prokaryotic as opposed to eukaryotic proteomes. Once we start thinking this way it is not easy to stop.
Author's response: We agree with all of this. "Goods thinking" will certainly provide a different perspective.
Reviewer 2: Eugene Koonin (NCBI, NLM, NIH, United States)
This is an interesting and entertaining essay on "horizontal genomics" and the inadequacy of the Tree of Life hypothesis. To me, the most appealing part of the article is Table 1 and the accompanying text where the authors introduce Samuelson's classification of goods and advocate its use in phylogenomics for an evolutionary classification of genes. This classification is interesting and useful, and might even stick although I think the authors could have been more explicit in discussing it, for instance, whether some genes can and should be viewed as 'common goods' as opposed to 'public goods'.
Author's response: We feel this is part of a multi-disciplinary programme of research and worthy of further publication at a later stage. For now, we wished to present the model.
Without any pejorative implications, it is my impression that beyond this fresh interdisciplinary perspective, there is little in this manuscript that is genuinely novel. In more conventional terms, the "public goods" concept looks familiar. To honk my own horn for once, here is a quote from the abstract of a 2008 review article on genomics of Bacteria and Archaea: "...comparative genomics also shows that horizontal gene transfer (HGT) is a dominant force of prokaryotic evolution, along with the loss of genetic material resulting in genome contraction. A crucial component of the prokaryotic world is the mobilome, the enormous collection of viruses, plasmids and other selfish elements, which are in constant exchange with more stable chromosomes and serve as HGT vehicles. Thus, the prokaryotic genome space is a tightly connected, although compartmentalized, network, a novel notion that undermines the 'Tree of Life' model of evolution and requires a new conceptual framework and tools for the study of prokaryotic evolution" [84]. I believe the "public goods" view is right there, even though the language is different.
Author's response: We have, of course, built on previous work and in particular, we have been very aware of the body of work that has emphasized the role of HGT, the problems with the ToL and the need for a 'new conceptual framework'. We feel we have cited many of the reviewers manuscripts and we naturally give as much credit as we can in the available space for others who have made these valuable contributions.
I should further note that the authors could have been more specific about their understanding of the "Tree of Life Hypothesis". What is that hypothesis that they consider to be refuted by comparative genomics? Clearly, this cannot be Tree of Life sensu Darwin because in the 19th century (and for much of the 20th century as well), the very idea of evolving genes and genomes did not exist, and so the Tree of Life hypothesis could not have been properly explicated (the authors of this article do make a note to that effect). Neither is it the modern "Statistical Tree of Life" hypothesis (see our article with Maureen O'Malley in this thematic series [85]) because to refute that hypothesis, actual statistical analysis is required that would prove false previous conclusions on the detectability of a central trend in the "Forest of Life" [31]. It seems to me that the hypothesis McInerney et al. are so adamant about refuting is a straw man of "fully coherent evolution of (nearly) all genes in all genomes", with the implication that a 16S RNA tree or a tree of a small number of highly conserved genes could be an adequate Tree of Life. Surely, that hypothesis is blatantly false and hopeless, but it hardly has been ever formulated in those explicit terms. The original publications by Woese (e.g.,[6]) simply assumed that the Tree of Life was embodied in the 16S RNA phylogeny, without much conceptual analysis of what this assumption entailed. Conversely, in the genomic era, it has become clear early on that the Tree of Life concept needed serious revamping if it were to survive (e.g.,[14]). I think that the image of the straw man can be only implied by some publications defending the traditional Tree of Life even in the face of extensive HGT (e.g.,[25, 86]). Certainly, these authors were well aware of the wide spread of HGT and simply have chosen to emphasize what they saw as the continued importance and heuristic power of trees of universal genes. That latter idea can be meaningfully debated even now but to that end, it would help to formulate more clearly the hypothesis for which a replacement is proposed.
Author's response: We have been clearer in this revised version concerning ToL hypotheses - from the causal Tree as envisioned by Darwin and which is, we feel, still at the very heart of ToL hypotheses, to the modern searches for Trees among forests, which are more weakly causal, but nonetheless still focus on some weak tree-likeness. We have also addressed these ToL hypotheses in terms of an axiomatic approach.
In terms of 'refuting' the ToL hypotheses, we refute the causal notion of a Tree of Life because clearly it is false. We replace it with the causal idea that acquiring genetic goods, either vertically or horizontally, leads to the patterns we see today in the data and that it is not a "just so" story that can be represented by drawing a network, rather it is a causal story that says that genes (or portions of genes or collections of genes) are acquired in the same way that goods are acquired in the world of economics. We reject the causal notions of a ToL, not from the perspective of being incorrect analyses, but from the perspective of being inadequate as the highest-level hypothesis. To this end we have clarified our ideas about the regionalization of ToL hypotheses.
Reviewer 3: John Dupré (University of Exeter, UK)
This paper nicely summarises the decline of the tree in microbiology, and provides for philosophers a rare but paradigmatic account of what Imre Lakatos [87] called a degenerating research programme. The "hard core"--the commitment to an underlying tree--is protected at all cost, despite ever-growing bodies of contrary evidence, by an ever more elaborate "protective belt". The next stage in the Lakatosian picture of scientific progress is the rise of an alternative and progressive research programme, and of course this is the project to which the present paper aims to contribute.
Somewhat tangentially to the question of the merits of theories old and new, I have quite frequently heard the suggestion that one of the most pressing needs in promoting some of the more radical ideas arising from contemporary biology is to find alternative metaphors as effective as those that have become so widely entrenched and disseminated, from the selfish gene and the struggle for existence, to the tree of life. The idea of (some) genes as public goods is an original and interesting contribution to this need. The interchange of concepts between biology and economics has been a productive one for two centuries, and this suggests an exciting new addition to this tradition.
Author's response: Just to clarify - we see the public goods hypothesis as providing not only a metaphor (clearly the Tree of Life provided a diagram/metaphor that could be used to describe evolving cellular life), but we see the Public Goods hypothesis as a description of the process of evolution - genes as goods that can be utilized, exchanged, protected, etc. So, while we would say that this is a metaphor, it is also a very real description of how genes are used by cells, viruses, plasmids etc. Goods thinking implies process as well as pattern.
Second Review by John Dupré
I did not mean to imply that metaphors were suspect tools in science; quite the opposite: they are crucial to scientific practice. In this regard, I agree with the authors about the importance of finding the appropriate concepts for evolutionary analysis.
First review by John Dupré
There are, of course, a few questions that will need to be pursued further before this metaphor becomes widely accepted. Most obviously, and fundamental to the whole debate from which the suggestion arises, is the extent to which genes are really non-excludable goods. I take it that all genes are non-rival, unless perhaps for some very special situations involving competition within a species. Tree aficionados, then, will take all genes to be club goods, excluded to all except for a club often containing no more than the members of a species. Although different clubs may, by reason of homology, have access to the same gene, there is no trading between clubs and eventually their products will presumably drift apart. It is worth noting that the clubs may be a lot bigger than has often been supposed. Contrary to a strict interpretation of McInerney et al.'s remark that 'animals... do not generally share their genes with animals of other species' it now appears that there is a great deal more hybridisation than was once supposed [88]. But while this may produce larger clubs and perhaps even clubs with fuzzy membership rules, this is a long way from a fully non-excludable public good.
Author's response: We call this hypothesis the "Public Goods" hypothesis to emphasise that genes, by virtue of using the same four (five) nucleotides, by using triplets of nucleotides in codons, by widespread use of the exact same genetic code and by virtue of known mechanisms of gene transfer, have the theoretical property of being public goods, but might find themselves in reality being part of a club (because of variant genetic code, function of the encoded protein, etc.). Goods are generally found somewhere on a gradient between one extreme of description and another, the categories are not discrete. However, there is indeed a programme of research in trying to understand the extent to which genes can be viewed, in reality, as public, private, club or common goods.
The important question to begin with, anyhow, is whether the public good concept is useful for understanding the evolution of prokaryotes, and the extent to which it remains so for various parts of the eukaryote, or perhaps just the sexual, world can wait. Two billion years of cellular evolution would make a good start. I take it that economists tend to think of a public good as something easily available to anyone. An interpretation of this for the evolutionary case might be, a public good gene is one such that any lineage for which it would be useful, i.e. that would be fitter with the addition of this genetic resource, will find it. I leave microbiologists to say how close reality comes to this, but I suppose that it would be unusual at best to achieve this fully. As McInerney et al. say, there is a good deal of variation in the ease with which different genes can be horizontally transferred, and there is also variation in the competence of different lineages to acquire genes. It might be in the end that a more literal-minded exploration of this metaphor would lead to a quite complex mapping of the various channels and obstacles to genetic trade.
Central to the variation just mentioned between degrees of excludability of genes, McInerney et al. suggest a dichotomy between informational and operational genes, and it is operational genes, due to the greater simplicity of their embedding in the functioning of the organism, that are liable to be public goods. Here the analogy with economics begins to limp. In the economic context information is a key example of a public good, perhaps in the age of the internet it has become the most important example of a potentially public good. It is the informational character of genes that underlies the non-rival character central to the possibility of their being public goods. Perhaps one way out of this rather confusing situation would be to replace the dichotomy just mentioned with one between information-processing genes as opposed to mere informational genes (i.e. operational genes). Alternatively, as a general sceptic about dichotomies, I am more tempted to suspect that this is more of a continuum of embeddedness and transferability, and as such might fit well enough into the mapping suggested at the end of the last paragraph.
Author's response: While this manuscript has been written, a very important manuscript [58]has emerged that has updated the complexity hypothesis and we have written about this in the revised version of the paper.
A final reflection on the public goods analogy is the following. Perhaps the most fundamental issue involving public goods in economics is the possibility of free riders to which it gives rise; and of course the possibility of free riding has figured in many evolutionary discussions. It would be a strong endorsement of the public goods metaphor if parallel issues could be discovered in prokaryote evolution. In some sense a cell or a cell lineage that avoids the cost of carrying a gene (say antibiotic resistance) that is not currently needed, safe in the 'knowledge' that some other lineages were keeping it readily available, might be said to free-ride. Is there a story to be told about the division of the costs of maintaining the stock of genetic resources in an otherwise free genetic commons? If so, the metaphor might show itself productive as well as expository.
Author's response: Indeed free riders do exist - plasmids that are non-conjugative can only transfer with the assistance of conjugative plasmids and so these are candidates for the category of 'free-riders', though this is only a suggestion. As we said previously, the current manuscript is designed to propose the Public Goods hypothesis and to propose "goods thinking" instead of "tree-thinking". Future work will be needed to evaluate free-riders, clubs, genetic commons, etc.
In summary, I am not yet convinced that the public goods hypothesis is a metaphor with the potential to do all the theoretical and public relations work formerly carried out by the Tree of Life. But it is at worst an intriguing way of raising a range of interesting questions, and may yet develop into a powerful and productive intellectual tool.
Reviewer 4: Gregory Morgan (College of Arts and Letters, Stevens Institute of Texhnology, United States)
Over the last two centuries, there have been many instances of the lateral exchange of ideas between biology and economics. Famously, Darwin was inspired by Malthus's work on reasons for declining living conditions in 18th century England [89, 90]. Social Darwinists like Herbert Spencer thought that biological concepts like "survival of the fittest" also applied in economic contexts [91]. More recently, game theory developed outside of biology has been used to analyze evolutionary stable strategies [92].
McInerney et al. propose another exchange: that biologists should co-opt the economic concept of public goods for biology and think of genes or sets of homologous genes as public goods. They cite the economist Paul Samuelson as the originator of the idea of public goods, although there are earlier versions of the concept going back as far as John Locke's discussion of property [41].
Author's response: We have now made this comment in the main body of the manuscript.
If the Public Goods Hypothesis is advanced as a metaphor, then it might supplement the tree of life. Presumably, McInerney et al. do not treat the Public Goods Hypothesis as a mere metaphor since they claim the Public Goods Hypothesis is an alternative to and indeed a replacement of the Tree of Life Hypothesis. What is literally true of (many) genes, they contend, is that they share with public goods the properties of being non-rival and non-excludible.
Author's response: This is correct, we do not see the Public Goods hypothesis as providing an alternative as a wooly metaphor, we feel that it is a sensible way of looking at how genes are treated by evolving entities - as goods that might or might not be used in different circumstances and as such, these genes have properties that are also recognized in things like cups of coffee and air.
What these concepts mean in a biological context is not made completely clear. By non-excludible, they say, "it is impossible or a least very difficult to exclude the good from being available to everybody." In the biological case, presumably one replaces "everybody" with "every genome" or perhaps "every genotype over a certain amount of time." Depending on what time scale we select, a gene might vary in its excludability. Perhaps McInerney et al. could quantify "very difficult" with a certain probability of horizontal exchange in a given unit of time to make what counts as a public good in biology more precise.
Author's response: We have cited the very important paper by Cohen et al. where they quantify the rates of HGT across a large sample of genes and show how it correlates with the connectivity of the encoded protein product. However, the rate of HGT and excludability may be two different things, though this needs further investigation. We still have outstanding questions such as whether or not all the gene sequences within, say, a particular ribosomal protein family are so well adapted to the ribosome in which they find themselves that they are effectively excluded from ever becoming involved in an HGT event. Given the limits of what can be done in any one manuscript, we feel that this is a significant question that warrants investigation, but is outside the scope of the current manuscript.
Unfortunately, a gene's probability of transfer will vary depending on the nature of the recipient genome in question. The concept of being "non-rival," too, needs further elaboration in the biological context. The idea is that a gene can be laterally transferred into a different organism without being "used up." But what does it mean to say that a copy of a gene on one organism precludes its use in another organism? One way to examine this question would be to look at what effect transfers of the gene has on the fitness of its instances. If an increase in copy number of a gene in a population decreases the fitness of any given instance of the gene, then there is a sense that its adaptive utility is being "used up" and the various copies are to some extent rivals with one another. On this suggestion, being a rival is a matter of degree. At one extreme when the utility of a gene is "all used up" because of prolific copying there is now selection against the gene in the donor genome in question. Perhaps there are other ways also to elaborate what it means for a gene to be "used up," but the authors do not pursue them. In any case, as one attempts to make the Public Goods Hypothesis more precise, the hypothesis becomes more complicated.
Author's response: Goods are generally viewed as being somewhere along the gradient from one extreme to the other extreme and the neat classification of goods is often not possible in reality. We gave the example of clean air, which is normally a public good, but for deep-sea divers with bottled air, it becomes a private good available only to the owner of the tank of air. In terms of rival genes, if a gene becomes too common in a particular environment it is likely that there is overuse of the environment and therefore, genes can become rival. Again, we feel that this is part of a progressive research programme to evaluate these kinds of genes.
One virtue of the Tree of Life Hypothesis is its simplicity, especially before the use of reticulation to account for lateral gene transfer. It was applied to all of life and any organism could in theory be placed at one and only one place in the tree. The Public Goods Hypothesis is not as simple. While many (McInerney et al. say "perhaps most") genes can be thought of as public goods, others cannot. Some should be thought of as being "club goods" i.e., they are excludible but non-rival. Furthermore, as McInerney et al. point out, what type of good a gene is classified under will depend on context. The tree of life offers powerful visual images that summarize patterns of relatedness. Is it possible for the public goods hypothesis also to offer an efficient and powerful means of visualizing patterns of relatedness? It is not clear.
Author's response: First of all, we would contend that the Tree of Life hypothesis was indeed applied to all of organismal life, but not to all evolving entities - it conspicuously left out plasmids, viruses, phage etc. Simpler ideas are appealing and indeed parsimonious reasoning is a powerful argument that is applied for many explanations in biology. However, evolution is dynamic and in our opinion a dynamic, pluralistic interpretation of the evolution of life on the planet is needed. The elegance, or otherwise, of the model is subjective.
On a positive note, if McInerney et al. are correct in claiming that the public goods hypothesis predicts local tree-like structure and global non-tree-like patterns, then this is a significant point in favor of the hypothesis. To make this point more strongly, a quantitative dynamic model of public goods that shows how patterns like their Figure 1 might be produced would be of interest.
Author's response: We agree with this, but feel that quantitative analysis is best left for another manuscript. In this current paper, we are explaining the model.
To make the public good hypothesis more plausible and move it beyond a speculative hypothesis, it would be useful to quantify the evidence in its favor. McInerney et al. claim that their hypothesis describes the genomic data better than the tree of life, and they may be right, but they do not offer any quantitative measures of degree of fit. In the longer run, proponents the Public Goods Hypothesis need testable novel predictions that cannot be explained, or at least explained only poorly, with a tree, sets of trees, or trees with reticulated branches. In sum, the Public Goods Hypothesis is a cute idea, but needs further quantitative development before it rises to the level of a genuine challenger to the Tree of Life Hypothesis.
Reviewer 5: Davide Vecchi (Universidad de Santiago de Chile, Chile)
The idea of the authors is to use concepts originally formulated in economics in order to offer a categorisation of genetic resources. This interdisciplinary ethos is to be welcomed, if only because contemporary science is too compartmentalised. The big question is whether the ensuing categorisation is effectively carving nature in an interesting and heuristically useful way.
Heuristic power
The authors contend that the analogy of genes to public goods and club goods is at odds with the Tree of Life (ToL) hypothesis. They also argue that the idea that genetic resources can be categorised using the concepts of rival and excludable goods makes sense of various observations (e.g. that it seems difficult for prokaryotes to prevent other prokaryotes from eventually exploiting a particular genetic resource). There is no doubt that using such new categorisation is in principle heuristically useful. In fact, it could highlight phenomena that possibly were previously considered of secondary interest. For instance, consider the existence of genetic clubs: the public goods (PG) hypothesis emphasises the theoretical significance of questions such as "why do such clubs exist?" and highlights the importance of studying the phenomenon of genetic retention within clubs. Using different theoretical tools and analogies - even drawn from distantly related sciences - with the aim of understanding in novel ways biological reality is highly commendable.
Nevertheless, even though the PG hypothesis could generate interesting insights, many questions remain concerning its theoretical status. One is whether the PG hypothesis is on a better epistemic footing than the ToL hypothesis, as argued by the authors. Another is whether it is general enough to be applicable to all genetic resources. A third is whether it is general enough to be applicable to all kinds of shared resources. I will comment on these issues in turn while also asking unashamedly speculative questions.
Saving the phenomena
The authors claim that the ToL hypothesis is almost unique in having been modified so extensively from its original proposal. This seems to me an overstatement. An interesting aspect of the history of geocentrism concerns the creativity of astronomers and the variety of solutions they devised in order to save the observed phenomena. This process lasted nearly twenty centuries. Is the ubiquitous practice of devising "epicycles" (aka ad-hoc hypotheses) justifiable? Many philosophers of science have argued that it is not. As a matter of fact, it looks more like a functional element of science: defending one's hypothesis is necessary for the dialectical process of theory change. This could also mean that there is no expiry date for the ToL hypothesis, even though all that is left of the original proposal is a rather unimpressive "tree of 1%".
Author's response: We 'toned down' this sentence about the ToL being 'unique'. We recognize that it is not unique in being stretched so far from its original proposal. We have also been careful to say that the ToL if it is properly interpreted (though there are so many interpretations it is difficult to keep track) can be considered a regionalized hypothesis within the public goods hypothesis.
The problem always concerns the quality of the alternative to the mainstream hypothesis. When the authors sustain that the PG is the best explanation of the evidence of lateral connections between lineages, critics are bound to be sceptical, mainly because the PG hypothesis is designed in order to accommodate these data. The critical question is whether the PG hypothesis can bring something new to the fore (e.g. unexpected and successful predictions concerning novel kinds of phenomena). Can it?
Author's response: When we formulated this hypothesis in 2010 we proposed, privately, that there are more mechanisms of gene transfer that have yet to be discovered and then in 2011 there has been the publication of nanotubes being observed ferrying genes fro one cell to another [43]. We feel that goods thinking has many predictions concerning gene transfer, defence against transfer and so on.
Second review by Davide Vecchi
The authors clarify in what sense the PG hypothesis is a radical alternative to the tree of life hypothesis. They say that the essence of tree thinking is that evolution is a process of continuous divergence. Tree thinking is inconsistent with the existence of HGT and of the mobilome. The alternative is that evolution is a continuous process of sampling of genes from the public goods pool. From this perspective the tree of life hypothesis is the incorrect starting phylogenetic assumption, the wrong null or default hypothesis, the reason being that the "primitive evolutionary state" is the public state. Seeing evolution as a process of continuous divergence and seeing evolution as a process of sampling from a public pool of goods are two radically different perspectives.
Author's response: This is indeed what we have been trying to achieve for this manuscript. We feel you have summarized it very nicely.
Davide Vecchi continues
The epistemic advantages of the PG hypothesis are many: it accommodates the evidence in favour of the existence of extensive HGT; it "makes unsurprising" (i.e. explains) the inevitable existence of the mobilome (given the nature of the ancestral evolutionary state); it makes sense of the existence of many evolving entities that do not belong to the cellular level of biological organisation. In addition to such accommodating roles, however, the PG hypothesis also fulfils other epistemic roles: it focuses its research on the discovery of new mechanisms of gene transfer [43] as well as on the discovery of barriers to HGT that have evolved in the history of life; it encourages testing of the extent to which coalitions of genes or club goods affect evolutionary dynamics; it provides the theoretical basis for new experimental results and new predictions (such as the role of genomic connectivity [58]) etc. In all these senses the PG hypothesis is clearly more than a metaphor.
Author's response: Yes, we have been trying to infer that it is more than a metaphor - it describes something causal.
Unification
The aim of the ToL hypothesis is to unify: the pattern of evolution is assumed to be the same for all organisms, multi-cellular eukaryotes and prokaryotes alike. Nonetheless, it turns out that the ToL creates a big divide: there is a fracture between normal organisms (those for which trees can be constructed) and "freaks" (for which we cannot). The PG hypothesis attempts to provide a picture of biological evolution that does not treat microbial phylogenetics as a special case, and that tries to finally re-unify microbial freaks and eukaryotes. But I wonder whether the PG hypothesis runs the risk of creating a converse divide, one where eukaryotes assume the new role of freaks of nature. The PG hypothesis rests on the implicit assumption that it will eventually be discovered that the same interactive and cooperative dynamics that affect the world of microbes also affect the world of macrobes. However, what are the theoretical reasons behind this implicit assumption? Why should we consider the PG hypothesis as general enough to encompass all genetic resources, both prokaryotic and eukaryotic, given the different systems of inheritance? Finally, in the eventuality that micro and macrocosms turn out to be governed by deeply different processes, what will be the consequences for the old idea of biology as a unified science of all life?
Author's response: Obviously, the use of the word 'freaks' entails a particular perspective that may not be held by all. Multicellular organisms engage in hybridization, we have seen Wolbachia genomes with perfect pieces of their hosts DNA integrated, we see transposons in multicellular organisms, so for sure nobody is completely excluded from accessing goods - vertical descent ensures that goods are available. Although the ocean might be considered to be a pubic good, we don't all have to go for a swim. There are many theories for why multicellular eukaryotes engage less in HGT than single cell prokaryotes, but labeling one or the other as freaks seems unnecessary.
Second review by Davide Vecchi
I think the new axiomatic approach of the paper is problematic. In the first place, the two axioms presented by the authors strike me as not being uncontroversial. The authors call them in turns "axioms", "conditions" and "desiderata", showing that there might be some confusion about their ontological status. Clearly, axiom 2 was a recent empirical discovery, while axiom 1 has even deeper problems because, as it is formulated, is eminently ambiguous: what are the "evolving entities"? Why should we take all of them into consideration? And what does "highest level evolutionary picture" mean?
These are difficult questions.
Author's response: We have endeavoured to clear up some of these issues by stating that we mean all nucleotides that are to be found in a replicating system. The fact that axiom 2 is a consequence of recent scientific findings and not older findings does not negate its usefulness as a self-evident fact now.
Davide Vecchi continues
That the axioms are not self-evident can be shown very simply. It is sufficient to take Mayr's position into consideration. In a famous exchange with Woese, Mayr [93] proposed the following argument: evolution is about phenotypes; prokaryotes show uninteresting phenotypes; hence evolution is about eukaryotic phenotypes. Here we have, clearly, a biased conception of prokaryotes as "freaks" as well as an equally biased (i.e. non pluralistic) interpretation of axiom 1. The point is that, according to Mayr, the only evolutionarily important entities are phenotypes. Additionally, clearly not all kinds of evolving entities can be taken into account in order to build an informative evolutionary picture. For these reasons my opinion is that Mayr would deny the legitimacy of axiom 1, as would many other taxonomists. More generally, axiom 1 does not propose a solution to the problem of establishing what the units of evolution are. It is subject to interpretation, and until the interpretation favoured by the authors is not universally accepted, there will be division between accounts of prokaryotic and eukaryotic evolution. And there will be freaks.
Author's response: Our interpretation of Mayr's ideas are somewhat different. Mayr said that "Evolution is an affair of phenotypes. It is phenotypes, not genes, that are the objects (targets) of selection" [93]. Mayr, in advocating that there were just two fundamental kinds of organisms simply said that the phenotypic similarities of eubacteria and archaebacteria logically placed them into one category and the phenotypic diversity of the eukaryotes identified them as a different category. In contrast to what is being asserted here, Mayr said in the same manuscript "[...] the possession of certain ancestral characters is often the most characteristic feature of a taxon." Therefore, we do not believe that Mayr found archaebacterial and eubacterial phenotypes uninteresting - in fact he found their relative lack of phenotypic diversity to be very interesting indeed. So, we will have to differ on this issue and re-state that we feel that both axioms are indeed uncontroversial.
Sharing resources
My last comment concerns the way in which communal goods are conceptualised by the authors. They only refer, understandably, to genetic goods, without considering the eventuality that a variety of gene products or other higher-level (e.g. phenotypic) resources could be exchange material in the microcosm. In fact, DNA resources are not the only types of resources that can be transmitted and shared. Contemporary theoretical biology also emphasises ecological inheritance, namely the inheritance of the set of environmental resources that are needed for the reconstruction of the phenotype. Can the PG hypothesis be enlarged as to encompass all kinds of resources (i.e. genetic, phenotypic, ecological and environmental)?
Author's response: We feel that the Public Goods hypothesis emphasizes ecology much more than tree-thinking does, however we are careful to say that this current manuscript really does focus on the genetic elements and not on proteins, which have long been viewed through the lens of goods-thinking.
I am asking this because I believe that even cultural change can be partially understood by means of the conceptual tools introduced in this paper. In fact, in cultural change cross-lineage borrowing mediated by mobile elements is very common and some cultural items are clearly public goods. However, the big difference is that in culture shared resources and mobile elements are not solely genetic.
Put another way, the primacy of genes as the sole resource of evolutionary interest is criticised in many parts of "eukaryotic biology" (e.g. developmental biology). The same idea requires profound extensions in order to make sense of cultural evolution. Nonetheless, genetic resources seem to be the sole focus in this paper, and possibly in microbiology. I wonder what the authors think about the prospects of unifying the study of evolutionary processes under a framework that takes into account all kinds of material resources exchanged and shared between organisms and lineages.
Author's response: We have tried in this most recent draft of the manuscript to emphasise that genes do not exist in isolation from their genetic code, the functions of the proteins they produce or the content of the rest of the genome in which they find themselves. We are not sure if there is a unifying theory of all goods thinking, but it is certainly an avenue worth pursuing.