Papillomaviruses (PVs) infect almost all mammals and possibly amniotes and bony fishes. While most of them have no significant effects on the hosts, some induce physical lesions. Phylogeny of PVs consists of a few crown groups [1], among which AlphaPVs that infect primates including human have been well studied. They are associated to largely different clinical manifestations: non-oncogenic PVs causing anogenital warts, oncogenic and non-oncogenic PVs causing mucosal lesions, and non-oncogenic PVs causing cutaneous warts.
The PV genome consists of a double stranded circular DNA genome, roughly organized into three parts: an early region coding for six open reading frames (ORFs: E1, E2, E4, E5, E6 and E7) involved in multiple functions including viral replication and cell transformation; a late region coding for structural proteins (L1 and L2); and a non-coding regulatory region (URR) that contains the cis-elements necessary for replication and transcription of the viral genome.
The E5, E6, and E7 are known to act as oncogenes. The E6 protein binds to the cellular p53 protein [2]. The E7 protein binds to the retinoblastoma tumor suppressor gene product, pRB [3]. However, the E5 has been poorly studied, even though a high correlation between the type of E5 protein and the infection phenotype is observed. E5s, being present on the E2/L2 intergenic region in the genomes of a few polyphyletic PV lineages, are so diverged and can only be characterized by high hydrophobicity. No similar sequences have been found in the sequence database.
Willemsen et al. [4] provide valuable evidence on the origin and evolutionary history of E5 genes and their genomic environments. First, they tested common ancestry vs independent origins [5]. Because alignment can lead to biased testing toward the hypothesis of common ancestry [6], they took full account of alignment uncertainty [7] and conducted random permutation test [8]. Although the strong chemical similarity hampered decisive conclusion on the test, they could confirm that E5 may do code proteins, and have unique evolutionary history with far different topology from the neighboring genes.
Still, there is mysteries with the origin and evolution of E5 genes. One of the largest interest may be the evolution of hydrophobicity, because it may be the main cause of variable infection phenotype. The inference has some similarity in nature with the inference of evolutionary history of G+C contents in bacterial genomes [9]. The inference may take account of possible opportunity of convergent or parallel evolution by setting an anchor to the topologies of neighboring genes.

References

[1] Bravo, I. G., & Alonso, Á. (2004). Mucosal human papillomaviruses encode four different E5 proteins whose chemistry and phylogeny correlate with malignant or benign growth. Journal of virology, 78, 13613-13626. doi: 10.1128/JVI.78.24.13613-13626.2004
[2] Werness, B. A., Levine, A. J., & Howley, P. M. (1990). Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science, 248, 76-79. doi: 10.1126/science.2157286
[3] Dyson, N., Howley, P. M., Munger, K., & Harlow, E. D. (1989). The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science, 243, 934-937. doi: 10.1126/science.2537532
[4] Willemsen, A., Félez-Sánchez, M., & Bravo, I. G. (2019). Genome plasticity in Papillomaviruses and de novo emergence of E5 oncogenes. bioRxiv, 337477, ver. 3 peer-reviewed and recommended by PCI Evol Biol. doi: 10.1101/337477
[5] Theobald, D. L. (2010). A formal test of the theory of universal common ancestry. Nature, 465, 219–222. doi: 10.1038/nature09014
[6] Yonezawa, T., & Hasegawa, M. (2010). Was the universal common ancestry proved?. Nature, 468, E9. doi: 10.1038/nature09482
[7] Redelings, B. D., & Suchard, M. A. (2005). Joint Bayesian estimation of alignment and phylogeny. Systematic biology, 54(3), 401-418. doi: 10.1080/10635150590947041
[8] de Oliveira Martins, L., & Posada, D. (2014). Testing for universal common ancestry. Systematic biology, 63(5), 838-842. doi: 10.1093/sysbio/syu041
[9] Galtier, N., & Gouy, M. (1998). Inferring pattern and process: maximum-likelihood implementation of a nonhomogeneous model of DNA sequence evolution for phylogenetic analysis. Molecular biology and evolution, 15(7), 871-879. doi: 10.1093/oxfordjournals.molbev.a025991

An individual’s sexual phenotype is determined during development. Understanding which pathways are activated or repressed during the developmental stages leading to a sexually mature individual, for example by studying gene expression and how its level is biased between sexes, allows us to understand the functional aspects of dimorphic phenotypes between the sexes.

Several studies have quantified the differences in transcription between the sexes in mature individuals, showing the extent of this sex-bias and which functions are affected. There is, however, less data available on what occurs during the different phases of development leading to this phenotype, especially in species with specific developmental strategies, such as hemimetabolous insects. While many well-studied insects such as the honey bee, drosophila, and butterflies, exhibit an holometabolous development ("holo" meaning "complete" in reference to their drastic metamorphosis from the juvenile to the adult stage), hemimetabolous insects have juvenile stages that look similar to the adult stage (the hemi prefix meaning "half", referring to the more tissue-specific changes during development), as seen in crickets, cockroaches, and stick insects. Learning more about what happens during development in terms of the identity of genes that are sex-biased (are they the same genes at different developmental stages? What are their function? Do they exhibit specific sequence evolution rates? Is one sex over-represented in the sex-biased genes?) and their quantity over developmental time (gradual or abrupt increase in number, if any?) would allow us to better understand the evolution of sexual dimorphism at the gene expression level and how it relates to dimorphism at the organismic level.

Djordjevic et al (2021) studied the transcriptome during development in an hemimetabolous stick insect, to improve our knowledge of this type of development, where the organismic phenotype is already mostly present in the early life stages. To do this, they quantified whole-genome gene expression levels in whole insects, using RNA-seq at three different developmental stages. One of the interesting results presented by Djordjevic and colleagues is that the increase in the number of genes that were sex-biased in expression is gradual over the three stages of development studied and it is mostly the same genes that stay sex-biased over time, reflecting the gradual change in phenotypes between hatchlings, juveniles and adults. Furthermore, male-biased genes had faster sequence divergence rates than unbiased genes and that female-biased genes.

This new information of sex-bias in gene expression in an hemimetabolous insect allowed the authors to do a comparison of sex-biased genes with what has been found in a well-studied holometabolous insect, Drosophila. The gene expression patterns showed that four times more genes were sex-biased in expression in that species than in stick insects. Furthermore, the increase in the number of sex-biased genes during development was quite abrupt and clearly distinct in the adult stage, a pattern that was not seen in stick insects. As pointed out by the authors, this pattern of a "burst" of sex-biased genes at maturity is more common than the gradual increase seen in stick insects.

With this study, we now know more about the evolution of sex-biased gene expression in an hemimetabolous insect and how it relates to their phenotypic dimorphism. Clearly, the next step will be to sample more hemimetabolous species at different life stages, to see how this pattern is widespread or not in this mode of development in insects.

References

Djordjevic J, Dumas Z, Robinson-Rechavi M, Schwander T, Parker DJ (2021) Dynamics of sex-biased gene expression during development in the stick insect Timema californicum. bioRxiv, 2021.01.23.427895, ver. 6 peer-reviewed and recommended by Peer Community in Evolutionary Biology. https://doi.org/10.1101/2021.01.23.427895

Natural populations do not consist of only perfectly adapted individuals. If they did, of course, there would be no fodder for evolution by natural selection. And natural selection is operating all the time, winnowing out less well adapted phenotypes through differential reproduction and survival. Demonstrations of natural selection modifying characters-state distributions to bring phenotypes closer to their optima abound in the evolution literature, with examples of short- and long-term changes in phenotype and allele frequencies.  

However, evolutionary biologists know that populations cannot reach their adaptive peaks. Natural selection is tracking a moving target, always with some generations of lag time. The adaptive landscape is multidimensional, so the optimal combination of multiple character states may be impossible because of constraints and trade-offs. Natural selection does not operate alone or in isolation – new mutations and migrants that were selected under other conditions will inject locally non-adaptive genetic variation and genetic drift can change allele frequencies in random directions. We understand these processes that generate and maintain less advantageous variants on a continuous gradient from an optimal phenotype in a fitness landscape. More puzzling are heritable polymorphisms with distinct morphologies, physiologies or behaviours maintained in populations despite their measurably lower reproductive success. But a complete model of evolution must also be able to accommodate these Darwinian paradoxes.

Raymond et al. (2023) investigate one such Darwinian paradox: In humans, male homosexual mate preference is heritable and is associated with a large reduction in offspring production but nonetheless occurs at relatively high frequencies in most human populations. Furthermore, multiple studies have found that homosexual men come from families that are, on average, larger than those of heterosexual men and that homosexual men have, on average, higher birth rank than do heterosexual men, i.e., having more older siblings and, particularly, more older brothers. Two types of mechanisms consistent with these observations have been proposed: 1) An evolutionary mechanism of sex-antagonistic pleiotropy, whereby highly fecund mothers are more likely to produce homosexual sons, and 2) A mechanistic explanation whereby successive male pregnancies alter the uterine environment by increasing the probability of an immune reaction by the mother to her male fetus, altering development of sexually dimorphic brain structures relevant to sexual orientation.

In this article, the authors explore these two mechanisms of sex-antagonistic effects (AE) and fraternal birth order effects (FBOE) and test how well they account for patterns of male homosexuality in population and family data. Clearly, these two effects are somewhat confounded because high birth ranks can only occur in large families. If, indeed, the probability of male homosexuality increases with increasing numbers of (maternal) older brothers, homosexual males will be more common in larger families. Similarly, if high female fecundity leads to a higher probability of male homosexuality via sex-antagonistic effects, homosexual males will, on average, have more older brothers. To disentangle the actions of these two effects the authors modelled the relationship between birth rank and population fecundity and investigated whether AE or FBOE modified this relationship for homosexual men.  Simulation results were compared with aggregated population data from 13 countries.  Family data on individuals’ sexual preference, birth rank and number of male and female siblings from France, Greece and Indonesia were analysed with generalised linear models and Bayesian approaches to test for a signal of AE or FBOE. 

These analyses revealed a significant older-brother effect (FBOE) explaining patterns of occurrence of homosexuality in population and family data but no significant independent sex-antagonistic effect (AE). Thus larger family sizes of homosexual men appear due to the older-brother effect, with individuals of high birth rank coming necessarily from large sibships. The simulation approach also revealed that modelling a fraternal birth order effect (FBOE), such that individuals with more older brothers are more likely to be homosexual, generates an artefactual older sister effect simply because homosexual men are overrepresented at higher birth ranks. Older-sister effects reported in the literature may, therefore, be statistical artefacts of an underlying older-brother effect.

This paper is interesting for a number of reasons. It does an excellent job of explaining, identifying and dealing with estimation biases and testing for artefactual relationships generated by collinearity. It applies state-of-the art analytical/statistical tools. It breaks down two colinear effects and shows that only one really explains phenotypic variation. This is a great example of how to disentangle correlated variables that may or may not both contribute to trait variation. But most intriguingly, we are left without evidence for an evolutionary mechanism that compensates the large fitness cost associated with male homosexuality in humans. How can we explain high heritability maintained in the face of strong directional selection that should erode heritable genetic variation? The usual suspects include cryptic compensatory mechanisms yet to be discovered or flawed estimates of selection or heritability. For example, data on heritability of male homosexual mate preference in humans come from twin studies and twins share birth rank as well as alleles. Thus it is possible that heritability is over-estimated, including the environmental component associated with birth rank. 

If, as the authors demonstrate here, birth rank is the strongest predictor of male homosexual mate preference, selection may be acting on a non-heritable plastic component of phenotypic variation. This could explain why heritable variation is not exhausted by selection, rendering the paradox less paradoxical, but fails to provide an adaptive explanation for the maintenance of male homosexual mate preference. 

References

Raymond M., Turek D., Durand V., Nila S., Suryobroto B., Vadez J., Barthes J., Apostolou M. and Crochet P.-A. (2023) Increased birth rank of homosexual males: disentangling the older brother effect and sexual antagonism hypothesis. bioRxiv, 2022.02.22.481477, ver. 4 peer-reviewed and recommended by Peer Community in Evolutionary Biology. https://doi.org/10.1101/2022.02.22.481477

Human economic activity is responsible for the vast majority of ongoing extinction, but that does not mean lineages are being affected willy-nilly. For amphibians [1] and South African flowering plants [2], young species have a somewhat higher than expected chance of being threatened with extinction. In contrast, older Australian marsupial lineages seem to be more at risk [3]. Both of the former studies suggested that situations leading to peripheral isolation might simultaneously increase ongoing speciation and current threat via small geographic range, while the authors of the latter study suggested that older species might have evolved increasingly narrow niches. Here, Andrew Tanentzap and colleagues [4] dig deeper into the putative links between species age, niche breadth and threat status. Across 500-some plant genera worldwide, they find that, indeed, ""younger"" species (i.e. from younger and faster-diversifying genera) were more likely to be listed as imperiled by the IUCN, consistent with patterns for amphibians and African plants. Given this, results from their finer-level analyses of conifers are initially bemusing: here, ""older"" (i.e., on longer terminal branches) species were at higher risk. This would make conifers more like Australian marsupials, with the rest of the plants being more like amphibians. However, here where the data were more finely grained, the authors detected a second interesting pattern: using an intriguing matched-pair design, they detect a signal of conifer species niches seemingly shrinking as a function of age. The authors interpret this as consistent with increasing specialization, or loss of ancestral warm wet habitat, over paleontological time. It is true that conifers in general are older than plants more generally, with some species on branches that extend back many 10s of millions of years, and so a general loss of suitable habitat makes some sense. If so, both the pattern for all plants (small initial ranges heightening extinction) and the pattern for conifers (eventual increasing specialization or habitat contraction heightening extinction) could occur, each on a different time scale. As a coda, the authors detected no effect of age on threat status in palms; however, this may be both because palms have already lost species to climate-change induced extinction, and because they are thought to speciate more via long-distance dispersal and adaptive divergence then via peripheral isolation.
Given how quickly ranges can change, how hard it is to measure niche breadth, and the qualitatively different time scales governing past diversification and present-day extinction drivers, this is surely not the last word on the subject, even for plants. However, even the hint of a link between drivers of extinction in the Anthropocene and drivers of diversification through the ages is intellectually exciting and, perhaps, even, somehow, of practical importance.

References

[1] Greenberg, D. A., & Mooers, A. Ø. (2017). Linking speciation to extinction: Diversification raises contemporary extinction risk in amphibians. Evolution Letters, 1, 40–48. doi: 10.1002/evl3.4
[2] Davies, T. J., Smith, G. F., Bellstedt, D. U., Boatwright, J. S., Bytebier, B., Cowling, R. M., Forest, F., et al. (2011). Extinction risk and diversification are linked in a plant biodiversity hotspot. PLoS Biology, 9:e1000620. doi: 10.1371/journal.pbio.1000620
[3] Johnson, C. N., Delean S., & Balmford, A. (2002). Phylogeny and the selectivity of extinction in Australian marsupials. Animal Conservation, 5, 135–142. doi: 10.1017/S1367943002002196
[4] Tanentzap, A. J., Igea, J., Johnston, M. G., & Larcombe, M. G. (2018). Range size dynamics can explain why evolutionarily age and diversification rate correlate with contemporary extinction risk in plants. bioRxiv, 152215, ver. 5 peer-reviewed and recommended by PCI Evol Biol. doi: 10.1101/152215

The tragic 2014-2016 Ebola outbreak that resulted in more than 28,000 cases and 11,000 deaths in West Africa [1] has been a surprise to the scientific community. Before 2013, the Ebola virus (EBOV) was known to produce recurrent outbreaks in remote villages near tropical rainforests in Central Africa, never exceeding a few hundred cases with very high virulence. Both EBOV’s ability to circulate for several months in large urban human populations and its important mutation rate suggest that EBOV’s virulence could evolve and to some extent adapt to human hosts [2]. Up to now, the high virulence of EBOV in humans was generally thought to be maladaptive, the virus being adapted to circulating in wild animal populations (e.g. fruit bats [3]). As a logical consequence, EBOV virulence could be expected to decrease during long epidemics in humans. The present paper by Sofonea et al. [4] challenges this view and explores how, given EBOV’s life cycle and known epidemiological parameters, virulence is expected to evolve in the human host during long epidemics. The main finding of the paper is that there is no chance that EBOV’s virulence decreases in the short and long terms. The main underlying mechanism is that EBOV is also transmitted by dead bodies, which limits the cost of virulence. In itself the idea that selection should select for higher virulence in diseases that are also transmitted after host death will sound intuitive for most evolutionary epidemiologists. The accomplishment of the paper is to make a very strong case that the parameter range where virulence could decrease is very small. The paper further provides scientifically grounded arguments in favor of the safe management of corpses. Safe burial of corpses is culturally difficult to impose. The present paper shows that in addition to instantaneously decreasing the spread of the virus, safe burial may limit virulence increase in the short term and favor of less virulent strains in the long term. Altogether these results make a timely and important contribution to the knowledge and understanding of EBOV.

References

[1] World Health Organization. 2016. WHO: Ebola situation report - 10 June 2016.

[2] Kupferschmidt K. 2014. Imagining Ebola’s next move. Science 346: 151–152. doi: 10.1126/science.346.6206.151

[3] Leroy EM, Kumulungui B, Pourrut X, Rouquet P, Hassanin A, Yaba P, Délicat A, Paweska, Gonzalez JP and Swanepoel R. 2005. Fruit bats as reservoirs of Ebola virus. Nature 438: 575–576. doi: 10.1038/438575a

[4] Sofonea MT, Aldakak L, Boullosa LFVV and Alizon S. 2017. Can Ebola Virus evolve to be less virulent in humans? bioRxiv 108589, ver. 3 of 19th May 2017; doi: 10.1101/108589