The unique challenges associated with living on an island often result in organisms displaying a specific suite of traits commonly referred to as “island syndrome” (Adler and Levins, 1994; Burns, 2019; Baeckens and Van Damme, 2020). Large phenotypic shifts such as changes in size (e.g. shifts to gigantism or dwarfism, Lomolino, 2005) or coloration (Doutrelant et al., 2016) abound in the literature. However, less obvious phenotypes may also play a key role in adaptation to islands.

One such trait, reduced immune function, has important implications for the future of island populations in the face of anthropogenic-induced changes. Due to lower parasite pressure caused by a less diverse and less virulent parasite population, island hosts may show a decrease in immune defenses (Beadell et al., 2006; Pérez‐Rodríguez et al., 2013). However, this hypothesis has been challenged, as many studies have found ambiguous or conflicting results (Matson, 2006; Illera et al., 2015).

While most previous work has examined various immunological parameters (e.g., antibody concentrations), here, Barthe et al. (2022) take the novel approach of examining molecular signatures of immune genes. Using comparative genomic data from 34 different species of birds the authors examine the ratio of synonymous substitutions (i.e., not changing an amino acid) to non-synonymous substitutions (i.e., changing an amino acid) in innate and acquired immune genes (Pn/Ps ratio). Because population sizes on islands are lower which will affect molecular evolution, they compare these results to data from 97 control genes.  Assuming relaxed selection on islands predicts that the difference between the Pn/Ps ratio of immune genes and of control genes (ΔPn/Ps) is greater in island species compared to mainland ones.

As with previous work the authors found that the results differ depending on the category of immune genes. Both forms of innate defense: beta-defensins and Toll-like receptors did not show higher ΔPn/Ps for island populations. As these genes still have a higher Pn/Ps than control genes, the authors argue these results are in line with these genes being under purifying selection but lacking an “island effect”. Instead, the authors argue that demographic effects (i.e., reductions in Ne) may lead to the decreased immunity documented in other studies. In contrast, there was a reduction in Pn/Ps in MHC II genes, known to be under balancing selection. This reduction was stronger in island species and thus the authors argue that this is the only class of genes where a role for relaxed selection can be invoked. 

Together these results demonstrate that the changes in immunity experienced by island species are complex and that different categories of immune genes can experience different selective pressures. By including control genes in their study, they particularly highlight the importance of accounting for shifts in Ne when examining patterns of island species evolution. Hopefully, this kind of framework will be applied to other taxa to determine if these results are widespread or more specific to birds. 

References

Adler GH, Levins R (1994) The Island Syndrome in Rodent Populations. The Quarterly Review of Biology, 69, 473–490. https://doi.org/10.1086/418744

Baeckens S, Van Damme R (2020) The island syndrome. Current Biology, 30, R338–R339. https://doi.org/10.1016/j.cub.2020.03.029

Barthe M, Doutrelant C, Covas R, Melo M, Illera JC, Tilak M-K, Colombier C, Leroy T, Loiseau C, Nabholz B (2022) Evolution of immune genes in island birds: reduction in population sizes can explain island syndrome. bioRxiv, 2021.11.21.469450, ver. 4 peer-reviewed and recommended by Peer Community in Evolutionary Biology. https://doi.org/10.1101/2021.11.21.469450

Beadell JS, Ishtiaq F, Covas R, Melo M, Warren BH, Atkinson CT, Bensch S, Graves GR, Jhala YV, Peirce MA, Rahmani AR, Fonseca DM, Fleischer RC (2006) Global phylogeographic limits of Hawaii’s avian malaria. Proceedings of the Royal Society B: Biological Sciences, 273, 2935–2944. https://doi.org/10.1098/rspb.2006.3671

Burns KC (2019) Evolution in Isolation: The Search for an Island Syndrome in Plants. Cambridge University Press, Cambridge. https://doi.org/10.1017/9781108379953

Doutrelant C, Paquet M, Renoult JP, Grégoire A, Crochet P-A, Covas R (2016) Worldwide patterns of bird colouration on islands. Ecology Letters, 19, 537–545. https://doi.org/10.1111/ele.12588

Illera JC, Fernández-Álvarez Á, Hernández-Flores CN, Foronda P (2015) Unforeseen biogeographical patterns in a multiple parasite system in Macaronesia. Journal of Biogeography, 42, 1858–1870. https://doi.org/10.1111/jbi.12548

Lomolino MV (2005) Body size evolution in insular vertebrates: generality of the island rule. Journal of Biogeography, 32, 1683–1699. https://doi.org/10.1111/j.1365-2699.2005.01314.x

Matson KD (2006) Are there differences in immune function between continental and insular birds? Proceedings of the Royal Society B: Biological Sciences, 273, 2267–2274. https://doi.org/10.1098/rspb.2006.3590

Pérez-Rodríguez A, Ramírez Á, Richardson DS, Pérez-Tris J (2013) Evolution of parasite island syndromes without long-term host population isolation: parasite dynamics in Macaronesian blackcaps Sylvia atricapilla. Global Ecology and Biogeography, 22, 1272–1281. https://doi.org/10.1111/geb.12084

As plants cannot run from their enemies, natural selection has favoured the evolution of diverse chemical compounds (phytochemicals) to protect them against herbivores and pathogens. This provides an opportunity for plant feeders to exploit these compounds to combat their own enemies. Indeed, it is widely known that herbivores use such compounds as protection against predators [1]. Recently, this reasoning has been extended to pathogens, and elegant studies have shown that some herbivores feed on phytochemical-containing plants reducing both parasite abundance within hosts [2] and their virulence [3].
Suffering less from parasites is clearly beneficial for infected herbivores. Why then, is this behaviour not fixed in nature? There are, at least, two possible explanations. First, feeding on ‘medicinal’, often toxic, plants may impose costs upon uninfected individuals. Second, parasites may evolve resistance to such chemicals. Whereas the first possibility has been explored, and is taken as evidence for ‘self-medication’ [3], the second hypothesis requires investigation. A recent study by Palmer-Young et al. [4] fills this gap. This article reports evolution of resistance to two different phytochemicals, alone and in combination, in the trypanosome Crithidia bombi, a bumble bee (Bombus impatiens) parasite. To show this, the authors experimentally evolved a strain of C. bombi in the presence of thymol, eugenol or both simultaneously. These phytochemicals are commonly found in the nectar of several plant species, in particular those of the Lamiaceae, a family containing several aromatic herbs. Prior to selection both phytochemicals reduced C. bombi growth by about 50%. However, C. bombi rapidly evolved resistance in both single and the double phytochemical treatments. Moreover, no cost of resistance was detected when evolved parasites were placed in the ancestral, phytochemical-free environment. Therefore, resistance to phytochemicals would be expected to spread rapidly in natural populations of C. bombi. Clearly, thus, the herbivore strategy of sequestering plant secondary chemical compounds as a defence against their pathogens should fail. The question then is ‘why do they still do it’? Can self-medication work in the longer-term for bumblebees?
Well, yes. The very fact that resistance evolved shows that resistance is not fixed in natural C. bombi populations. This is surprising considering that resistance is not costly. This might be due to a number of reasons. Firstly, there may be costs of resistance that were not detected in this experiment. Second, it may not be possible to evolve universal resistance to the heterogeneity present in the phytochemical environment. Indeed, phytochemical environments are highly varied in time and space and bumblebees will visit different plants presenting different phytochemical cocktails throughout the season. Furthermore, migration of bees from populations exposed to different phytochemicals may prevent the fixation of one resistance type.
Or, it may be self-medication behaviour itself that prevents the evolution of resistance? Indeed, in the same way that infected bees seek cooler temperatures to slow growth of a parasitoid fly [5], they may also seek a more varied diet with diverse phytochemicals to which the parasite cannot evolve, but which reduces parasite growth. Further understanding of arthropod self-medication may thus be instrumental to prevent the observed worldwide decline of pollinators [6]. Furthermore, it may inform on mechanisms that prevent rapid evolution of drug resistance in other systems.

References

[1] Duffey SS. 1980. Sequestration of plant natural products by insects. Annual Review of Entomology 25: 447-477. doi: 10.1146/annurev.en.25.010180.002311

[2] Richardson LL et al. 2015. Secondary metabolites in floral nectar reduce parasite infections in bumblebees. Proceedings of the Royal Society of London B 282: 20142471. doi: 10.1098/rspb.2014.2471

[3] Lefèvre T et al. 2010. Evidence for trans-generational medication in nature. Ecology Letters 13: 1485-93. doi: 10.1111/j.1461-0248.2010.01537.x

[4] Palmer-Young EC, Sadd BM, Adler LS. 2017. Evolution of resistance to single and combined floral phytochemicals by a bumble bee parasite. Journal of Evolutionary Biology 30: 300-312. doi: 10.1111/jeb.13002

[5] Müller CB, Schmid-Hempel P. 1993. Exploitation of cold temperature as defence against parasitoids in bumblebees. Nature 363: 65-67. doi: 10.1038/363065a0

[6] Potts SG et al. 2010. Global pollinator declines: trends, impacts and drivers. Trends in Ecology and Evolution 25: 345-353. doi: 10.1016/j.tree.2010.01.007

This manuscript [1] investigates the evolutionary history of the DAN gene family—a group of genes important for embryonic development of limbs, kidneys, and left-right axis speciation. This gene family has also been implicated in a number of diseases, including cancer and nephropathies. DAN genes have been associated with the inhibition of the bone morphogenetic protein (BMP) signaling pathway. Despite this detailed biochemical and functional knowledge and clear importance for development and disease, evolution of this gene family has remained understudied. The diversification of this gene family was investigated in all major groups of vertebrates. The monophyly of the gene members belonging to this gene family was confirmed. A total of five clades were delineated, and two novel lineages were discovered. The first lineage was only retained in cephalochordates (amphioxus), whereas the second one (GREM3) was retained by cartilaginous fish, holostean fish, and coelanth. Moreover, the patterns of chromosomal synteny in the chromosomal regions harboring DAN genes were investigated. Additionally, the authors reconstructed the ancestral gene repertoires and studied the differential retention/loss of individual gene members across the phylogeny. They concluded that the ancestor of gnathostome vertebrates possessed eight DAN genes that underwent differential retention during the evolutionary history of this group. During radiation of vertebrates, GREM1, GREM2, SOST, SOSTDC1, and NBL1 were retained in all major vertebrate groups. At the same time, GREM3, CER1, and DAND5 were differentially lost in some vertebrate lineages. At least two DAN genes were present in the common ancestor of vertebrates, and at least three DAN genes were present in the common ancestor of chordates. Therefore the patterns of retention and diversification in this gene family appear to be complex. Evolutionary slowdown for the DAN gene family was observed in mammals, suggesting selective constraints. Overall, this article puts the biomedical importance of the DAN family in the evolutionary perspective.

References

[1] Opazo JC, Hoffmann FG, Zavala K, Edwards SV (2020) Evolution of the DAN gene family in vertebrates. bioRxiv, 794404, ver. 3 peer-reviewed and recommended by PCI Evolutionary Biology. doi: 10.1101/794404

Monnin et al. [1] here studied how Drosophila populations are affected when exposed to a high virulent endosymbiotic wMelPop Wolbachia strain and why virulent vertically transmitting endosymbionts persist in nature. This virulent wMelPop strain has been described to be a blocker of dengue and other arboviral infections in arthropod vector species, such as Aedes aegypti. Whereas it can thus function as a mutualistic symbiont, it here acts as an antagonist along the mutualism-antagonism continuum symbionts operate. The wMelPop strain is not a natural occurring strain in Drosophila melanogaster and thus the start of this experiment can be seen as a novel host-pathogen association. Through experimental evolution of 17 generations, the authors studied how high temperature affects wMelPop Wolbachia virulence and Drosophila melanogaster survival. The authors used Drosophila strains that were selected for late reproduction, given that this should favor evolution to a lower virulence. Assumptions for this hypothesis are not given in the manuscript here, but it can indeed be assumed that energy that is assimilated to symbiont tolerance instead of reproduction may lead to reduced virulence evolution. This has equally been suggested by Reyserhove et al. [2] in a dynamics energy budget model tailored to Daphnia magna virulence evolution upon a viral infection causing White fat Cell disease, reconstructing changing environments through time.
Contrary to their expectations for vertically transmitting symbionts, the authors did not find a reduction in wMelPop Wolbachia virulence during the course of the experimental evolution experiment under high temperature. Important is what this learns for virulence evolution, also for currently horizontal transmitting disease epidemics (such as COVID-19). It mainly reflects that evolution of virulence for new host-pathogen associations is difficult to predict and that it may take multiple generations before optimal levels of virulence are reached [3,4]. These optimal levels of virulence will depend on trade-offs with other life history traits of the symbiont, but also on host demography, host heterogeneity, amongst others [5,6]. Multiple microbial interactions may affect the outcome of virulence evolution [7]. Given that no germ-free individuals were used, it can be expected that other components of the Drosophila microbiome may have played a role in the virulence evolution. In most cases, microbiota have been described as defensive or protective for virulent symbionts [8], but they may also have stimulated the high levels of virulence. Especially, given that upon higher temperatures, Wolbachia growth may have been increased, host metabolic demands increased [9], host immune responses affected and microbial communities changed [10]. This may have resulted in increased competitive interactions to retrieve host resources, sustaining high virulence levels of the symbiont.
A nice asset of this study is that the phenotypic results obtained in the experimental evolution set-up were linked with wMelPop density measurement and octomom copy number quantifications. Octomom is a specific 8-n genes region of the Wolbachia genome responsible for wMelPop virulence, so there is a link between the phenotypic and molecular functions of the involved symbiont. The authors found that density, octomom copy number and virulence were correlated to each other. An important note the authors address in their discussion is that, to exclude the possibility that octomom copy number has an effect on density, and density on virulence, the effect of these variables should be assessed independently of temperature and age. The obtained results are a valuable contribution to the ongoing debate on the relationship between wMelPop octomom copy number, density and virulence.

References

[1] Monnin, D., Kremer, N., Michaud, C., Villa, M., Henri, H., Desouhant, E. and Vavre, F. (2020) Experimental evolution of virulence and associated traits in a Drosophila melanogaster – Wolbachia symbiosis. bioRxiv, 2020.04.26.062265, ver. 4 peer-reviewed and recommended by PCI Evol Biol. doi: https://doi.org/10.1101/2020.04.26.062265
[2] Reyserhove, L., Samaey, G., Muylaert, K., Coppé, V., Van Colen, W., and Decaestecker, E. (2017). A historical perspective of nutrient change impact on an infectious disease in Daphnia. Ecology, 98(11), 2784-2798. doi: https://doi.org/10.1002/ecy.1994
[3] Ebert, D., and Bull, J. J. (2003). Challenging the trade-off model for the evolution of virulence: is virulence management feasible?. Trends in microbiology, 11(1), 15-20. doi: https://doi.org/10.1016/S0966-842X(02)00003-3
[4] Houwenhuyse, S., Macke, E., Reyserhove, L., Bulteel, L., and Decaestecker, E. (2018). Back to the future in a petri dish: Origin and impact of resurrected microbes in natural populations. Evolutionary Applications, 11(1), 29-41. doi: https://doi.org/10.1111/eva.12538
[5] Day, T., and Gandon, S. (2007). Applying population‐genetic models in theoretical evolutionary epidemiology. Ecology Letters, 10(10), 876-888. doi: https://doi.org/10.1111/j.1461-0248.2007.01091.x
[6] Alizon, S., Hurford, A., Mideo, N., and Van Baalen, M. (2009). Virulence evolution and the trade‐off hypothesis: history, current state of affairs and the future. Journal of evolutionary biology, 22(2), 245-259. doi: https://doi.org/10.1111/j.1420-9101.2008.01658.x
[7] Alizon, S., de Roode, J. C., and Michalakis, Y. (2013). Multiple infections and the evolution of virulence. Ecology letters, 16(4), 556-567. doi: https://doi.org/10.1111/ele.12076
[8] Decaestecker, E., and King, K. (2019). Red queen dynamics. Reference module in earth systems and environmental sciences, 3, 185-192. doi: https://doi.org/10.1016/B978-0-12-409548-9.10550-0
[9] Kirk, D., Jones, N., Peacock, S., Phillips, J., Molnár, P. K., Krkošek, M., and Luijckx, P. (2018). Empirical evidence that metabolic theory describes the temperature dependency of within-host parasite dynamics. PLoS biology, 16(2), e2004608. doi: https://doi.org/10.1371/journal.pbio.2004608
[10] Frankel-Bricker, J., Song, M. J., Benner, M. J., and Schaack, S. (2019). Variation in the microbiota associated with Daphnia magna across genotypes, populations, and temperature. Microbial ecology, 1-12. doi: https://doi.org/10.1007/s00248-019-01412-9

Why is there such variation across species and populations in the rate at which individuals show wear and tear as they get older? Several compelling theoretical explanations have been developed on the conditions under which selection allows for or prevents senescence; a notable one being that proposed by George C Williams in 1957 based on the idea of antagonistic pleiotropy (Williams, 1957). One of the testable predictions of this theory is that, in populations where adults experience higher mortality, senescence is expected to be faster. This is one of the most influential predictions of the paper, being intuitive (when individuals are less likely to survive to later age classes, we expect weakened selection on traits that would avoid senescence in these classes), and fitting with ‘live fast, die young’ life history framing. As such, it has been widely incorporated into how we think about the evolution of senescence and has received considerable support in comparative studies across species and populations.  

However, it would be misleading to sit back at this point and think we have ‘solved’ the problem of understanding variation in senescence, and how this is linked with mortality. It turns out that the Williams 1957 paper is hotly contested by theoreticians: for the past 30 years – with increasing focus in the last 4 years – a growing body of models and opinion pieces have proposed flaws in the paper itself and in how it has been interpreted (Abrams, 1993; André and Rousset, 2020; Day and Abrams, 2020; Moorad et al., 2019). Central to several of these critiques is that explicit consideration of density dependence (not considered in Williams’ original paper) changes the conditions under which his predictions hold. A new preprint by de Vries, Gallipaud and Kokko brings further clarity to such critiques of the original paper (Vries et al., 2023). 

Beyond just continuing the tradition of critiquing Williams’ prediction, however, de Vries et al. provide a clear guide that is accessible to non-theoreticians about the issues with William’s prediction, and the way in which density dependence and how it operates can change when we expect senescence to occur. Rather than reiterate their points here, we suggest a close reading of the paper itself, along with an excellent overview of the paper in a recent blog by Daniel Nettle (Nettle, 2022). In brief, the paper starts by synthesizing earlier theoretical and empirical studies on the topic and presenting a very simple model to highlight how – in the absence of density dependence – Williams’ prediction does not hold because of the unregulated population growth, which is necessarily higher when there is low mortality. As a result, for a lineage with low mortality, any fitness advantage of placing offspring into the lineage later (i.e. selection for reduced senescence) is exactly cancelled out by the fact that earlier-produced offspring have higher fitness returns. 

They then present a more complex framework, which incorporates realistic mortality distributions, trade-offs between survival and reproduction, and use a series of 10 scenarios of density dependence (and whether this acts on survival or fecundity, and also whether it depends on a threshold or stochastic, or exerts continuing pressure on the trait) to explore selection on fitness-associated traits with age depending on extrinsic mortality. This then generates a range of results for when the Williams prediction holds, when there is no link between mortality and senescence, and when there is an ‘anti-Williams’ result – i.e., where senescence is slower when there is a high mortality. As has been shown in earlier studies, density dependence and how it operates matters, and Williams’ prediction holds most when density dependence affects juvenile age classes (in their model, when adults are less likely to produce them – i.e. there is density dependence on fecundity; or when there is less recruitment into the adult population due to, for example, competition among juveniles). 

So, perhaps we are now at a point where we can lay to rest the debate on the issues specifically with Williams’ original paper, and instead consider more broadly the key factors to measure when predicting patterns of senescence, and what is tangible for empiricists to quantify in their studies. Here, de Vries et al. provide some helpful insights both into the limitations of their approach and what modelling should be done moving forward, and into how we can link existing studies (for example comparing senescence among populations with varying predation pressure) to the theoretical predictions. At the heart of the latter is understanding the mechanism of density-dependent regulation – does it affect survival or fecundity, which age classes are most sensitive, and how do key traits depend on density? – and this is often difficult to measure in field studies.

And from all this we can learn that even very intuitive and extensively discussed concepts in biology do not always have as firm theoretical underpinnings as assumed, and – as should not be surprising – biology is complex and rather than one clear pattern being predicted, this can depend on a multitude of factors. 

REFERENCES

Abrams PA (1993) Does increased mortality favor the evolution of more rapid senescence? Evolution, 47, 877–887. https://doi.org/10.1111/j.1558-5646.1993.tb01241.x

André J-B, Rousset F (2020) Does extrinsic mortality accelerate the pace of life? A bare-bones approach. Evolution and Human Behavior, 41, 486–492. https://doi.org/10.1016/j.evolhumbehav.2020.03.002

Day T, Abrams PA (2020) Density Dependence, Senescence, and Williams’ Hypothesis. Trends in Ecology & Evolution, 35, 300–302. https://doi.org/10.1016/j.tree.2019.11.005

Moorad J, Promislow D, Silvertown J (2019) Evolutionary Ecology of Senescence and a Reassessment of Williams’ ‘Extrinsic Mortality’ Hypothesis. Trends in Ecology & Evolution, 34, 519–530. https://doi.org/10.1016/j.tree.2019.02.006

Nettle AD (2022) Live fast and die young (maybe). https://www.danielnettle.org.uk/2022/02/18/live-fast-and-die-young-maybe/ (accessed 2.27.23).

de Vries C, Galipaud M, Kokko H (2023) Extrinsic mortality and senescence: a guide for the perplexed. bioRxiv, 2022.01.27.478060, ver. 5 peer-reviewed and recommended by Peer Community in Evolutionary Biology. https://doi.org/10.1101/2022.01.27.478060

Williams GC (1957) Pleiotropy, natural selection, and the evolution of senescence. Evolution, 11, 398–411. https://doi.org/10.1111/j.1558-5646.1957.tb02911.x