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Widmer, A.

Publications and source records attributed to Widmer, A..

At least 19 recordsLinked to original sources

Harnessing distinct tissue-resident immune niches via S100A9/TLR4 improves ketone, lipid, and glucose metabolism

Immunometabolism contributes to the development of metabolic diseases. Yet, how certain metabolic disorders, such as insulin deficiency (ID), influence immune cell function is poorly understood. Here, we observe that ID rearranges the immune landscape of the liver, causing a decrease in T cells and an increase in Kupffer cells, accompanied by a shift in the transcriptome and polarization of the latter. Treating ID mice with the protein S100A9 rescues the polarization and lipid-related changes caused by ID in the KCs, and rescues hypertriglyceridemia and hyperketonemia in a TLR4-dependent manner. Additionally, S100A9 acts on other immune niches to increase glucose uptake in skeletal muscle, improving hyperglycemia. In summary, the S100A9-TLR4 axis is a new tool to harness immune cells for improving ID-related metabolic dysfunction.

physiology↗

Soil heterogeneity and pleiotropy contribute to polygenic soil adaptation during postglacial range expansion in an alpine plant

1) Plants colonized new abiotic environments during postglacial range expansions. Little is known about whether populations adapt to different soil conditions during range expansion and, if so, which mechanisms underlie presumably polygenic adaptation. It remains unclear how pleiotropy and soil heterogeneity contribute to such adaptation. 2) We studied 43 populations of Dianthus sylvestris with characterized soil conditions along its postglacial range expansion in the Alps. We leveraged genome-wide data and variation in multiple soil variables to identify polygenic signatures of selection in soil-associated alleles using environmental association analysis, generalized dissimilarity models, and polygenic scores. 3) We found signatures of selection in 814 single nucleotide polymorphisms (SNPs) and the largest magnitude of allele frequency change in candidate SNPs associated with K, Mg, and Al. Candidate genes showed higher pleiotropy than randomly sampled genes. We found soil heterogeneity shaping the populations adaptive genetic variation in the landscape. 4) Our results suggest that populations of D. sylvestris adapted to contrasting soil chemical properties during postglacial range expansion through polygenic adaptation. Pleiotropy likely plays an important role in polygenic adaptation to novel selective pressures and soil heterogeneity is an important factor contributing to the maintenance of adaptive genetic variation.

evolutionary biology↗

Adaptation of protein stability to thermally heterogeneous environments

Proper protein folding is essential for biological function, and its disruption can lead to disease, reduced fitness, or death. The ability of a protein to maintain its folded conformation is thus critical for life, making it a key target of adaptive evolution. However, protein stability is sensitive to environmental factors, particularly temperature, which can threaten phenotypic integrity and organismal survival under thermal changes. Despite its importance, the influence of complex thermal environments - characterized here by mean temperature, thermal fluctuations, and environmental heterogeneity - on the evolution of protein stability remains poorly understood. To address this, we developed a mathematical framework that combines two well-established models: a population genetic model describing species distributed across habitats with distinct thermal environments, and a thermodynamic model of protein stability incorporating temperature-dependent enthalpy and entropy contributions. We focus on two-state proteins that alternate between folded and unfolded states and assume that allelic fitness is maximized in proteins that achieve an optimal balance between flexibility and rigidity. Using this framework, we performed an invasion analysis of mutations (sensu adaptive dynamics framework) affecting three thermodynamic parameters that fully determine protein stability profiles. Where possible, we derived analytical expressions for evolutionarily optimal thermodynamic parameters and complemented these with numerical solutions. Our results show that mean temperature and thermal fluctuations have orthogonal effects on thermodynamic parameters, underscoring the need to consider both when studying protein stability adaptation. We further examined thermally heterogeneous environments, where subpopulations connected by migration experience different mean temperatures, identifying conditions that favor either local (specialist) or global (generalist) adaptation. Our results may explain why one thermodynamic parameter shows little association with thermal adaptation and suggest that local adaptation is more likely for proteins with stability profiles limited to narrow temperature ranges. Additionally, our analysis reveals whether a locally adapted protein originated in a colder or warmer habitat. Finally, we identified trade-offs in thermodynamic parameters that influence local or global adaptation. This study offers key predictions about protein evolution in complex thermal environments and lays the groundwork for developing practical tools to understand how temperature shapes adaptation and biodiversity.

evolutionary biology↗

Trait evolution linked to climatic shifts contributes to adaptive divergence in an alpine carnation (Dianthus sylvestris)

Populations expanding to new habitats may encounter novel selection regimes which can lead to ecotype formation. In the Alps, elevation corresponds to steep ecological gradients, along which ecotype formation has occurred in many species. The majority of alpine plant species are perennial and little is known about how selection acts across different stages of their life-cycles and how fitness trade-offs shape adaptive processes in perennials. We investigated how selection at opposite ends of elevational gradients has driven ecotype formation in Dianthus sylvestris, a perennial herb that expanded its ecological niche to low elevation habitats after the Last Glacial Maximum. Through a multi-year reciprocal transplant experiment including parental populations and recombinant crosses we assessed fitness under natural conditions and dissect how adaptation is mediated by different fitness components with inherent trade-offs, and pinpoint the contribution of growth and reproductive traits to this process. We show that the evolution of local adaptation proceeded by selection acting primarily through reproduction and survival at low and high elevation, respectively. At low elevation the primary contribution to adaptation was third year reproduction, concomitant with a left skewed age distribution. At high elevation the contribution to adaptation and the age distribution were more dispersed across the life cycle. We found that large, early flowering plants have a consistent fitness advantage. This was mediated by direct selection favoring large size through reproductive output at low elevation, and early flowering through the probability to produce seeds at high elevation. Our results indicate that the selection regime imposed by the warm low elevation habitat led to the evolution of an ecotype exhibiting a life-history strategy characterized by high investment in rapid growth and early reproduction. In contrast, the high elevation strategy favors high investment in self-maintenance. Our results suggest that weakening of a key fitness trade-off associated with resource allocation contributed to the evolution of distinct ecotypes in this perennial plant species.

evolutionary biology↗

Life history traits mediate elevational adaptation in a perennial alpine plant

O_LISpatially divergent natural selection drives adaptation to contrasting environments and the evolution of ecotypes. Understanding this process in perennial plants is challenging because natural selection acts on multiple life history traits linked by fitness trade-offs. C_LIO_LIIn a multi-year reciprocal transplant experiment of high and low elevation populations of the alpine carnation Dianthus carthusianorum in the Central Alps, we tested how different stages of the life cycle contribute to adaptation. Moreover, we used matrix population models to infer the specific contributions of individual life stages to fitness, coupled with trade-off analyses. C_LIO_LIWe found genotype x environment interactions consistent with elevational adaptation both in single fitness components linked to reproduction and survival, and in integrative fitness estimates. Adaptation at low elevation is driven by early reproduction, in contrast to an opposite strategy at high elevation. Adaptive life-history differences between populations originating from low and high elevations are mediated by environmental effects on plant growth and trade-offs between reproduction and survival. C_LIO_LIOur work reveals elevational ecotypes of the perennial alpine plant D. carthusianorum that express alternative life history strategies in response to climatic differences shaping resource allocation. C_LI

evolutionary biology↗

Evolution of sex-biased gene expression during transitions to separate sexes in the Silene genus

Sexual dimorphism is widespread among species with separate sexes and its extent is thought to be governed by the differential expression of thousands of genes between males and females (known as Sex-Biased Genes, hereafter SBGs). SBGs have been studied in numerous species, but rarely in a comparative way, which curtails our understanding of their evolution, especially during multiple independent transitions to separate sexes. We sequenced the transcriptomes of nine dioecious species, two gynodioecious species (separate females and hermaphrodites) and two hermaphrodite species from the Silene genus. Our dataset provides access to three independent transitions to dioecy (dating from less than 1 Myo to about 11 Myo). We demonstrated that male-biased expression emerges first during a transition to separate sexes, later followed by female-biased genes. Furthermore, we showed that, despite a mixture of selective regimes, positive selection significantly affects the evolution of some SBGs. Overall, this study provides new insights on the causes of SBG evolution during transitions to separate sexes. TeaserThis study describes the evolution of sex-biased gene expression during a transition to separate sexes in plants.

evolutionary biology↗

Sequential colonization events with restricted gene flow in a widespread European carnation species

The key questions relating to the evolutionary processes underlying plant colonization success pertain to the geographic origin of the source population(s), the location of the migration routes, the extent to which genetic diversity is reduced via founder effects, and the extent of gene flow among populations during expansion. However, these questions must still be addressed for perennial herbaceous plants with large geographic distributions. We investigated the colonization history of Dianthus carthusianorum (the Carthusian Pink), one of the most widespread European carnation species. We called genome-wide 236,964 SNPs from a large sample across the D. carthusianorum distribution range, and used up-to-date population genomics approaches (approximate Bayesian computation Random-Forest method, ABC-RF) to infer population demographic history. Spatial genetic structure and diversity analyses and demographic inferences indicated successive East-West colonization events by the Carthusian Pink. ABC-RF also revealed gene flow during colonization, but only among geographically close populations. This study provides important insights into the colonization processes of herbaceous perennial species belonging to one of Europes most diverse plant genera.

evolutionary biology↗

Population genomics and epigenomics provide insights into the evolution of facultative asexuality in plants

Many organisms, particularly plants, are facultatively asexual. Because asexual reproduction is beneficial for the short term but costly for the long term, during the range expansion, natural selection should act on the genetic controls of asexuality in these facultatively asexual organisms. However, the genomic evidence of natural selection driving asexuality remains scarce, and the evolutionary consequences of facultatively asexuality on the genomic and epigenomic diversity remain controversial. Here, by analyzing population genomes and epigenomes of Spirodela polyrhiza (L.) Schleid., a facultatively asexual plant that flowers rarely, we show that this plant has the lowest genomic diversity and DNA methylation levels among all studied multicellular eukaryotes. Within species, demographic history and the frequency of asexual reproduction jointly determined intra-specific variations of genomic diversity and DNA methylation levels. Genome-wide scans revealed that multiple genes involved in flowering and embryogenesis were under positive selection, consistent with the hypothesis that natural selection drove the evolution of asexuality during the recent habitat expansions in this plant. Together, these results provide new insights into the evolution of plant reproductive systems and suggest that natural selection can drive the evolutionary changes of asexuality, which in turn alters the levels of genomic and epigenomic diversity.

evolutionary biology↗

Ancient methicillin-resistant Staphylococcus aureus: expanding current knowledge using molecular epidemiological characterization of a Swiss legacy collection

Few methicillin-resistant Staphylococcus aureus (MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes. We accessed 451 ancient (1965-1987) Swiss MRSA isolates, stored in the Culture Collection of Switzerland. We determined phenotypic antimicrobial resistance (AMR) and performed Illumina short-read sequencing on all isolates and long-read sequencing on a selection with Oxford Nanopore Technology. For context, we included 103 publicly available international genomes from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmec cassette types, AMR, and virulence genes. Among the 451 ancient Swiss MRSA isolates, we found 17 sequence types (STs) of which 11 have been previously described. Two STs were novel combinations of known loci and six isolates carried previously unsubmitted MLST alleles, representing five new STs (ST7843, ST7844, ST7837, ST7839, and ST7842). Most isolates (83% 376/451) represented ST247-MRSA-I isolated in the 1960s, followed by ST7844 (6% 25/451), a novel single locus variant (SLV) of ST239. Analysis by cgMLST indicated that isolates belonging to ST7844-MRSA-III cluster within the diversity of ST239-MRSA-IIII. Early MRSA were predominantly from clonal complex (CC) 8. From 1980 to the end of the 20th century we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally. The combined analysis of 1761 ancient and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss and international MRSA across time.

microbiology↗

Detecting directional epistasis and dominance from cross-line analyses in Alpine populations of Arabidopsis thaliana

The contribution of non-additive genetic effects to the genetic architecture of fitness, and to the evolutionary potential of populations, has been a topic of theoretical and empirical interest for a long time. Yet, the empirical study of these effects in natural populations remains scarce, perhaps because measuring dominance and epistasis relies heavily on experimental line crosses. In this study, we explored the contribution of dominance and epistasis in natural alpine populations of Arabidopsis thaliana, for two fitness traits, the dry biomass and the estimated number of siliques, measured in a greenhouse. We found that, on average, crosses between inbred lines of A. thaliana led to mid-parent heterosis for dry biomass, but outbreeding depression for estimated number of siliques. While heterosis for dry biomass was due to dominance, we found that outbreeding depression for estimated number of siliques could be attributed to the breakdown of beneficial epistatic interactions. We simulated and discussed the implication of these results for the adaptive potential of the studied populations, as well as the use of line-cross analyses to detect non-additive genetic effects.

evolutionary biology↗

Genomic evidence for rapid speciation and gene flow between sympatric carnivorous Nepenthes pitcher plants

Speciation can result from both neutral and adaptive processes, but their relative importance and the factors exerting selective pressures are incompletely understood. In theory, interspecific gene flow could suffice to reverse speciation, or else erode neutral divergence and expose traits and underlying genes whose divergence is due to selection. Hence, introgression can shed light on selection during the speciation process. Here we study mixed assemblages of carnivorous Nepenthes pitcher plants, which frequently produce natural hybrids yet maintain distinct phenotypes. Using ddRAD-seq markers, we characterize divergence and introgression for eight Nepenthes species that grow sympatrically in communities of three to seven species at four locations in Southeast Asia, totalling 22 populations. The sympatric species fell into two discrete classes of high and low divergence. Five lineages with high divergence displayed little recent introgression in tests of location-dependent allele sharing (ABBA-BABA) despite the presence of some natural hybrids. However, all five lineages appear to have introgressed in the more distant past, as revealed by coalescent models with Approximate Bayesian Computation. In the same locations occur three further sympatric species with low genetic divergence. These incipient species also showed some natural hybrids, but in addition both ABBA-BABA tests and ABC suggested very recent or ongoing introgression, raising the question how divergence is maintained in these hybrid zones. One trait possibly involved in maintenance of divergence against gene flow might be the carnivorous pitcher traps, whose morphology showed greater divergence than expected under neutral evolution (Pst-Fst) in the introgressing species pair N. hemsleyana and N. rafflesiana t.f..

evolutionary biology↗

Adaptive evolution of carnivory in Nepenthes pitcher plants: a comparative transcriptomics and proteomics perspective

While trait diversity associated with evolutionary radiations is easily recognized, their function and adaptive relevance often remain elusive. Here we study the evolution of carnivory genes in Nepenthes, an iconic radiation of carnivorous pitcher plants. We investigate 13 species chosen to represent the diversity of nutrient acquisition strategies, geography and climates covered by the genus. Using a combination of proteomics and transcriptomics, we discovered that Nepenthes secrete hundreds of enzymes and antimicrobial proteins into their digestive fluids. Further genes related to plant carnivory were uncovered by analyses of gene expression changes induced by experimental feeding of starved Nepenthes traps. Feeding status appears to affect the relative abundance of nearly 35% of all expressed genes, and may be accompanied by a strong physiological shift away from photosynthesis towards heterotrophy, proteolysis, and protein synthesis. Among the many thousand genes showing signatures of adaptive evolution in sequence or expression level within the Nepenthes radiation, the secreted pitcher fluid proteins and the carnivory-related genes were over-represented. A bias towards carnivory genes, and towards trap-expressed genes versus leaf-expressed genes, was also observed among the genes differing in expression in a young pair of sister species. Together, our results suggest that the molecular basis of the carnivorous syndrome was disproportionally targeted by positive selection during the Nepenthes radiation. This study demonstrates how the evolutionary relevance of putative key traits can be tested at the level of underlying genes.

evolutionary biology↗

Unravelling drivers of local adaptation through Evolutionary Functional-Structural Plant modelling

O_LILocal adaptation to contrasting environmental conditions along environmental gradients is a widespread phenomenon in plant populations, yet we lack a mechanistic understanding of how individual agents of selection contribute to local adaptation. C_LIO_LIHere, we developed a novel evolutionary functional-structural plant (E-FSP) model that simulates local adaptation of virtual plants along an environmental gradient. First, we validate the model by testing if it can recreate two elevational ecotypes of Dianthus carthusianorum occurring in the Swiss Alps. Second, we use the E-FSP model to disentangle the relative contribution of abiotic (temperature) and biotic (competition and pollination) selection pressures to elevational adaptation in D. carthusianorum. C_LIO_LIThe model reproduced the qualitative differences between the elevational ecotypes in two phenological (germination and flowering time) and one morphological trait (stalk height), as well as qualitative differences in four performance variables that emerge from GxE interactions (flowering time, number of stalks, rosette area and seed production). Our results suggest that elevational adaptation in D. carthusianorum is predominantly driven by the abiotic environment. C_LIO_LIOur approach shows how E-FSP models incorporating physiological, ecological and evolutionary mechanisms can be used in combination with experiments to examine hypotheses about patterns of adaptation observed in the field. C_LI

evolutionary biology↗

Climate-induced range shifts drive adaptive response via spatio-temporal sorting of alleles

Quaternary climate fluctuations drove many species to shift their geographic ranges, in turn shaping their genetic structures. Recently, it has been argued that adaptation may have accompanied species range shifts via the "sieving" of genotypes during colonisation and establishment. However, this has not been directly demonstrated, and knowledge remains limited on how different evolutionary forces, that are typically investigated separately, interacted to jointly mediate species responses to past climatic change. Here, through whole-genome resequencing of over 1200 individuals of the carnation Dianthus sylvestris coupled with integrated population genomic and gene-environment models, we reconstruct the past neutral and adaptive landscape of this species as it was shaped by the Quaternary glacial cycles. We show that adaptive responses emerged concomitantly with the post-glacial range shifts and expansions of this species in the last 20 thousand years. This was due to the spatial sorting of adaptive alleles through time, as populations expanded out of restrictive glacial refugia into the broader and more heterogeneous range of habitats available in the present-day inter-glacial. Our results reveal a tightly-linked interplay of migration and adaptation under past climate-induced range shifts that has acted to shape the spatial patterns of adaptive genetic variation we see in the species today.

evolutionary biology↗

The UV RESISTANCE LOCUS 8-Mediated UV-B Response Is Required Alongside CRYPTOCHROME1 For Plant Survival Under Sunlight In The Field

As sessile organisms, plants are subjected to fluctuating sunlight including potentially detrimental ultraviolet-B radiation (UV-B). In Arabidopsis thaliana, experiments under controlled conditions have shown that UV RESISTANCE LOCUS 8 (UVR8) controls photomorphogenic responses for acclimation and tolerance to UV-B; however, its long-term impacts on plant performance remain poorly understood in naturally fluctuating environments. Here we quantified the survival and reproduction of different Arabidopsis mutant genotypes in diverse field and laboratory conditions. We found that uvr8 mutants produced more fruits than wild type in growth chambers with artificial low UV-B conditions but not in natural field conditions. Importantly, independent double mutants of UVR8 and the blue-light photoreceptor gene CRYPTOCHROME 1 (CRY1) in two genetic backgrounds showed a drastic reduction in fitness in the field. UV-B attenuation experiments in field conditions and supplemental UV-B in growth chambers demonstrated that UV-B caused the conditional cry1 uvr8 lethality phenotype. RNA sequencing in different conditions revealed a large number of genes with statistical interaction of UVR8 and CRY1 mutations in the presence of UV-B in the field. Among them, Gene Ontology analysis identified enrichment of categories related to UV-B response, oxidative stress, photoprotection and DNA damage repair. Our study demonstrates the functional importance of the UVR8-mediated response across life stages in natura, which is partially redundant with CRY1, and provides an integral picture of gene expression associated with plant environmental responses under diverse environmental conditions.

plant biology↗

A target capture approach for phylogenomic analyses at multiple evolutionary timescales in rosewoods (Dalbergia spp.) and the legume family (Fabaceae)

Understanding the genetic changes associated with the evolution of biological diversity is of fundamental interest to molecular ecologists. The assessment of genetic variation at hundreds or thousands of unlinked genetic loci forms a sound basis to address questions ranging from micro-to macro-evolutionary timescales, and is now possible thanks to advances in sequencing technology. Major difficulties are associated with i) the lack of genomic resources for many taxa, especially from tropical biodiversity hotspots, ii) scaling the numbers of individuals analyzed and loci sequenced, and iii) building tools for reproducible bioinformatic analyses of such datasets. To address these challenges, we developed a set of target capture probes for phylogenomic studies of the highly diverse, pantropically distributed and economically significant rosewoods (Dalbergia spp.), explored the performance of an overlapping probe set for target capture across the legume family (Fabaceae), and built a general-purpose bioinformatics pipeline. Phylogenomic analyses of Dalbergia species from Madagascar yielded highly resolved and well supported hypotheses of evolutionary relationships. Population genomic analyses identified differences between closely related species and revealed the existence of a potentially new species, suggesting that the diversity of Malagasy Dalbergia species has been underestimated. Analyses at the family level corroborated previous findings by the recovery of monophyletic subfamilies and many well-known clades, as well as high levels of gene tree discordance, especially near the root of the family. The new genomic and bioinformatics resources will hopefully advance systematics and ecological genetics research in legumes, and promote conservation of the highly diverse and endangered Dalbergia rosewoods.

genomics↗

Identifying loci under selection via explicit demographic models

Adaptive genetic variation is a function of both selective and neutral forces. To accurately identify adaptive loci, it is thus critical to account for demographic history. Theory suggests that signatures of selection can be inferred using the coalescent, following the premise that genealogies of selected loci deviate from neutral expectations. Here, we build on this theory to develop an analytical framework to identify Loci under Selection via explicit Demographic models (LSD). Under this framework, signatures of selection are inferred through deviations in demographic parameters, rather than through summary statistics directly, and demographic history is accounted for explicitly. Leveraging on the property of demographic models to incorporate directionality, we show that LSD can provide information on the environment in which selection acts on a population. This can prove useful in elucidating the selective processes underlying local adaptation, by characterising genetic trade-offs and extending the concepts of antagonistic pleiotropy and conditional neutrality from ecological theory to practical application in genomic data. We implement LSD via Approximate Bayesian Computation and demonstrate, via simulations, that LSD has i) high power to identify selected loci across a large range of demographic-selection regimes, ii) outperforms commonly applied genome-scan methods under complex demographies, and iii) accurately infers the directionality of selection for identified candidates. Using the same simulations, we further characterise the behaviour of isolation-with-migration models conducive to the study of local adaptation under regimes of selection. Finally, we demonstrate an application of LSD by detecting loci and characterising genetic trade-offs underlying flower colour in Antirrhinum majus.

evolutionary biology↗

Dioecy in plants: an evolutionary dead end? Insights from a population genomics study in the Silene genus

About 15,000 angiosperm species ([~]6%) have separate sexes, a phenomenon known as dioecy. Early work reported a lower species richness in dioecious compared to non-dioecious sister clades, which was taken to suggest that dioecy might be an evolutionary dead end. More recently, phylogenetic analyses using different methodologies have challenged this conclusion. Here, we used a population genomics approach to look for evidence of evolutionary handicaps of dioecy in the Silene genus at the molecular level. We obtained RNA-seq data of individuals from several populations in 13 closely related species with different breeding systems: seven dioecious, three hermaphroditic and three gynodioecious species. We show that dioecy is associated with increased genetic diversity and a higher selection efficacy both against deleterious and for beneficial mutations while controlling for differences in population size. We conclude that, in the Silene genus, dioecious species bear no sign of mutational burden or upcoming extinction. On the contrary, dioecious species harbor a higher potential for adaptation than their non-dioecious relatives. Our results do not support the evolutionary dead end hypothesis and re-open the question why dioecy is rare in angiosperms.\n\nSignificance statementDioecy (=separate sexes) is much rarer in flowering plants compared to animals and other organisms. The \"dead-end hypothesis\" states that dioecious plant populations might experience evolutionary handicaps such as low seed dispersal (as only 50% of the individuals, the females, contribute), which might cause high genetic drift, low adaptation and ultimately extinction. Here we tested this hypothesis by focusing on the genus Silene and by comparing the population genetics of 13 dioecious and non-dioecious species. We found that dioecious Silene species exhibit lower genetic drift and more adaptation compared to their non-dioecious relatives. Our results thus reject the dead-end hypothesis and re-open the question of why dioecy is rare in flowering plants.

evolutionary biology↗