SEARCH · Search bioRxiv

Results for “Evolutionary Biology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

bioRxiv2015

The State of Software in Evolutionary Biology

With Next Generation Sequencing Data (NGS) coming off age and being routinely used, evolutionary biology is transforming into a data-driven science.\n\nAs a consequence, researchers have to rely on a growing number of increasingly complex software. All widely used tools in our field have grown considerably, in terms of the number of features as well as lines of code. In addition, analysis pipelines now include substantially more components than 5-10 years ago.\n\nA topic that has received little attention in this context is the code quality of widely used codes. Unfortunately, the majority of users tend to blindly trust software and the results it produces. To this end, we assessed the code quality of 15 highly cited tools (e.g., MrBayes, MAFFT, SweepFinder etc.) from the broader area of evolutionary biology that are used in current data analysis pipelines.\n\nWe also discuss widely unknown problems associated with floating point arithmetics for representing real numbers on computer systems. Since, the software quality of the tools we analyzed is rather mediocre, we provide a list of best practices for improving the quality of existing tools, but also list techniques that can be deployed for developing reliable, high quality scientific software from scratch.\n\nFinally, we also discuss journal and science policy as well as funding issues that need to be addressed for improving software quality as well as ensuring support for developing new and maintaining existing software.\n\nOur intention is to raise the awareness of the community regarding software quality issues and to emphasize the substantial lack of funding for scientific software development.

Evolutionary Biology↗

bioRxiv2014

The disruption of trace element homeostasis due to aneuploidy as a unifying theme in the etiology of cancer

#### #### ABSTRACT FOR SCIENTISTS: While decades of cancer research have firmly established multiple hallmarks of cancer 1,2, cancers genomic landscape remains to be fully understood. Particularly, the phenomenon of aneuploidy gains and losses of large genomic regions, i.e. whole chromosomes or chromosome arms and why most cancer cells are aneuploid remains enigmatic 3. Another frequent observation in many different types of cancer is the deregulation of the homeostasis of the trace elements copper, zinc and iron. Concentrations of copper are markedly increased in cancer tissue and the blood plasma of cancer patients, while zinc levels are typically decreased 49. Here we discuss the hypothesis that the disruption of trace element homeostasis and the phenomenon of aneuploidy might be linked. Our tentative analysis of genomic data from diverse tumor types mainly from The Cancer Genome Atlas (TCGA) project suggests that gains and losses of metal transporter genes occur frequently and correlate well with transporter gene expression levels. Hereby they may confer a cancer-driving selective growth advantage at early and possibly also later stages during cancer development. This idea is consistent with recent observations in yeast, which suggest that through chromosomal gains and losses cells can adapt quickly to new carbon sources 10, nutrient starvation 11 as well as to copper toxicity 12. In human cancer development, candidate driving events may include, among others, the gains of zinc transporter genes SLC39A1 and SLC39A4 on chromosome arms 1q and 8q, respectively, and the losses of zinc transporter genes SLC30A5, SLC39A14 and SLC39A6 on 5q, 8p and 18q. The recurrent gain of 3q might be associated with the iron transporter gene TFRC and the loss of 13q with the copper transporter gene ATP7B. By altering cellular trace element homeostasis such events might contribute to the initiation of the malignant transformation. Intriguingly, attenuation or overexpression of several of these metal transporter genes has been shown to lead to malignant cellular behavior in vitro. Consistently, it has been shown that zinc affects a number of the observed hallmarks of cancer characteristics including DNA repair, inflammation and apoptosis, e.g. through its effects on NF-kappa B signaling. We term this model the aneuploidy metal transporter cancer (AMTC) hypothesis and find it compatible with the cancer-promoting role of point mutations and focal copy number alterations in established tumor suppressor genes and oncogenes (e.g. MYC, MYCN, TP53, PIK3CA, BRCA1, ERBB2). We suggest a number of approaches for how this hypothesis could be tested experimentally and briefly touch on possible implications for cancer etiology, metastasis, drug resistance and therapy. #### #### ABSTRACT FOR KIDS: We humans are made up of many very small building blocks, which are called cells. These cells can be seen with a microscope and they know how to grow and what to do from the information on the DNA of their chromosomes. Sometimes, if this information is messed up, a cell can go crazy and start to grow without control, even in places of the body where it should not. This process is called cancer, a terrible disease that makes people very sick. Scientists do not understand exactly what causes cells to go crazy, so it would be good to find out. Many years ago, scientists observed that chromosomes in these cancer cells are missing or doubled but could not find an explanation for it. More recently, scientists have detected that precious metals to our bodies, which are not gold and silver, but zinc, iron and copper, are not found in the right amounts in these crazy cancer cells. There seems to be not enough zinc and iron but too much copper, and again, scientists do not really understand why. So there are many unanswered questions about these crazy cancer cells and in this article, we describe a pretty simple idea on how chromosome numbers and the metals might be connected: we think that the missing or doubled chromosomes produce less or more transporters of zinc, iron and copper. As a result, cancer cells end up with little zinc and too much copper and these changes contribute to their out-of-control growth. If this idea were true, many people would be excited about it. But first this idea needs to be investigated more deeply in the laboratory, on the computer and in the hospitals. Therefore, we put it out on the internet so that other people can also think about and work on our idea. Now there are plenty of ways to do exciting experiments and with the results, we will hopefully understand much better why cancer cells go crazy and how doctors could improve their therapies to help patients in the future. #### #### ABSTRACT FOR ADULTS: One hundred years ago, it was suggested that cancer is a disease of the chromosomes, based on the observations that whole chromosomes or chromosome arms are missing or duplicated in the genomes of cells in a tumor. This phenomenon is called aneuploidy and is observed in most types of cancer, including breast, lung, prostate, brain and other cancers. However, it is not clear which genes could be responsible for this observation or if this phenomenon is only a side effect of cancer without importance, so it is important to find out. A second observation from basic research is that concentrations of several micronutrients, especially of the trace elements zinc, copper and iron are changed in tumor cells. In this article, we speculate that aneuploidy is the reason for these changes and that together, these two phenomena are responsible for some of the famous hallmarks or characteristics that are known from cancer cells: fast growth, escape from destruction by the immune system and poor DNA repair. This idea is new and has not been tested yet. We name it the aneuploidy metal transporter cancer (AMTC) hypothesis. To test our idea we used a wealth of information that was shared by international projects such as the Human Genome Project or the Cancer Genome Atlas Project. Indeed, we find that many zinc, iron and copper transporter genes in the genome are affected by aneuploidy. While a healthy cell has two copies of each gene, some tumor cells have only one or three copies of these genes. Furthermore, the amounts of protein and the activities of these metal transporters seem to correlate with these gene copy numbers, at least we see that the intermediate molecules and protein precursors called messenger RNA correlate well. Hence, we found that the public data is compatible with our suggested link between metal transporters and cancer. Furthermore, we identified hundreds of studies on zinc biology, evolutionary biology, genome and cancer research that also seem compatible. For example, cancer risk increases in the elderly population as well as in obese people, it also increases after certain bacterial or viral infections and through alcohol consumption. Consistent with the AMTC hypothesis and in particular, the idea that external changes in zinc concentrations in an organ or tissue may kick off the earliest steps of tumor development, all of these risk factors have been correlated with changes in zinc or other trace elements. However, since additional experiments to test the AMTC hypothesis have not yet been performed, direct evidence for our hypothesis is still missing. We hope, however, that our idea will promote further research with the goal to better understand cancer as a first step towards its prevention and the development of improved anti-cancer therapies in the future.

Cancer Biology↗

bioRxiv2017

Genomic regression of claw keratin, taste receptor and light-associated genes inform biology and evolutionary origins of snakes

Regressive evolution of anatomical traits corresponds with the regression of genomic loci underlying such characters. As such, studying patterns of gene loss can be instrumental in addressing questions of gene function, resolving conflicting results from anatomical studies, and understanding the evolutionary history of clades. The origin of snakes coincided with the regression of a number of anatomical traits, including limbs, taste buds and the visual system. By studying the genomes of snakes, I was able to test three hypotheses associated with the regression of these features. The first concerns two keratins that are putatively specific to claws. Both genes that encode these keratins were pseudogenized/deleted in snake genomes, providing additional evidence of claw- specificity. The second hypothesis is whether snakes lack taste buds, an issue complicated by unequivocal, conflicting results in the literature. I found evidence that different snakes have lost one or more taste receptors, but all snakes examined retained at least some capacity for taste. The final hypothesis I addressed is that the earliest snakes were adapted to a dim light niche. I found evidence of deleted and pseudogenized genes with light- associated functions in snakes, demonstrating a pattern of gene loss similar to other historically nocturnal clades. Together these data also provide some bearing on the ecological origins of snakes, including molecular dating estimates that suggest dim light adaptation preceded the loss of limbs.

evolutionary biology↗

bioRxiv2017

A phylogenomic framework and timescale for comparative genomics and evolutionary developmental biology of tunicates

BackgroundTunicates are the closest relatives of vertebrates and are widely used as models to study the evolutionary developmental biology of chordates. Their phylogeny, however, remains poorly understood and to date, only the 18S rRNA nuclear gene and mitogenomes have been used to delineate the major groups of tunicates. To resolve their evolutionary relationships and provide a first estimate of their divergence times, we used a transcriptomic approach to build a phylogenomic dataset including all major tunicate lineages, consisting of 258 evolutionarily conserved orthologous genes from representative species.\n\nResultsPhylogenetic analyses using site-heterogeneous CAT mixture models of amino acid sequence evolution resulted in a strongly supported tree topology resolving the relationships among four major tunicate clades: 1) Appendicularia, 2) Thaliacea + Phlebobranchia + Aplousobranchia, 3) Molgulidae, and 4) Styelidae + Pyuridae. Notably, the morphologically derived Thaliacea are confirmed as the sister-group of the clade uniting Phlebobranchia + Aplousobranchia within which the precise position of the model ascidian genus Ciona remains uncertain. Relaxed molecular clock analyses accommodating the accelerated evolutionary rate of tunicates reveal ancient diversification (~450-350 million years ago) among the major groups and allow comparing their evolutionary age with respect to the major vertebrate model lineages.\n\nConclusionsOur study represents the most comprehensive phylogenomic dataset for the main tunicate lineages. It offers a reference phylogenetic framework and first tentative timescale for tunicates, allowing the direct comparison with vertebrate model species in comparative genomics and evolutionary developmental biology studies.

evolutionary biology↗

bioRxiv2017

Spatial resource heterogeneity increases diversity and evolutionary potential

Spatial heterogeneity is believed to be an evolutionary driver of biodiversity. Variability in the distribution of resource patches can allow an environment to support a wider variety of phenotypes for selection to act upon at the ecosystem level, which may lead to more species. However, the generality of this principle has not been thoroughly tested, as the relevant adaptive dynamics occur on evolutionary timescales. We overcame this challenge by performing experiments on populations of digital organisms in the Avida Digital Evolution Platform, in which we investigated the impact of spatial resource heterogeneity on phenotypic diversity. Since an important benefit of diversity may be increased evolutionary potential, we also tracked the probability of a complex trait evolving in the context of various levels of spatial heterogeneity. We found that spatial entropy and phenotypic diversity have a strong positive correlation and this relationship is consistent across various spatial configurations. Diversity also increases evolutionary potential, but has a much smaller impact than other components of environmental composition. The most important of these components was the mean number of resources present in locations across the environment, likely owing to the importance of building blocks for the evolution of complex features. These results suggest that a general relationship exists between spatial heterogeneity and diversity, beyond the specific ecosystems and timescales in which it has previously been studied. By examining this relationship in the context of phenotypic evolution, we advance a mechanistic understanding of the resulting dynamics. Moreover, our results suggest that the likelihood of evolving various traits can be impacted by the spatial configuration of patches in which these traits are advantageous. These findings have implications for both evolutionary biology and evolutionary computation, as generating and maintaining diversity is critical to all forms of evolution.

ecology↗

bioRxiv2017

De novo organelle biogenesis in the cyanobacterium TDX16 released from the green alga Haematococcus pluvialis

It is believed that eukaryotes arise from prokaryotes, which means that organelles can form in the latter. Such events, however, had not been observed previously. Here, we report the biogenesis of organelles in the endosymbiotic cyanobacterium TDX16 that escaped from its senescent/necrotic host cell of green alga Haematococcus pluvialis. In brief, organelle biogenesis in TDX16 initiated with cytoplasm compartmentalization, followed by de-compartmentalization, DNA allocation, and re-compartmentalization, as such two composite organelles-the primitive chloroplast and primitive nucleus sequestering minor and major fractions of cellular DNA respectively were formed. Thereafter, the eukaryotic cytoplasmic matrix was built up from the matrix extruded from the primitive nucleus; mitochondria were assembled in and segregated from the primitive chloroplast, whereby the primitive nucleus and primitive chloroplast matured into nucleus and chloroplast respectively; while most mitochondria turned into double-membraned vacuoles after matrix degradation. Results of pigment analyses, 16S rRNA and genome sequencing revealed that TDX16 is a phycocyanin-containing cyanobacterium resembling Chroococcidiopsis thermalis, which had acquired 9,017,401bp DNAs with 10301 genes form its host. Therefore, organelle biogenesis in TDX16 was achieved by hybridizing the acquired eukaryotic DNAs with its own ones and expressing the hybrid genome.\n\nOrganelle biogenesis in TDX16 results in its transition into a new eukaryotic alga TDX16-DE, which provides a reference to re-understand the development, structure, function and association of organelles in eukaryotes and the reasons behind them, and has implications on other sections of biology, particularly cancer biology and evolutionary biology: (1) the formation and maturation of the small organelle-less nascent cancer cells share striking similarities with TDX16 development and transition, so, it is most likely that cancer cells arise from bacteria; (2) organelle biogenesis in TDX16 uncovers a way of new organelle and new single-celled eukaryote formation, and in light of which, the ancestral organelles were likely formed in rather than transformed form the endosymbiotic prokaryotes that had acquired their hosts DNAs.

cell biology↗

bioRxiv2017

Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution

Detecting the genomic changes underlying phenotypic changes between species is a main goal of evolutionary biology and genomics. Evolutionary theory predicts that changes in cis-regulatory elements are important for morphological changes. Here, we combine genome sequencing and functional genomics with genome-wide comparative analyses to investigate the fate of regulatory elements in lineages that lost morphological traits. We first show that limb loss in snakes is associated with widespread divergence of limb regulatory elements. We next show that eye degeneration in subterranean mammals is associated with widespread divergence of eye regulatory elements. In both cases, sequence divergence results in an extensive loss of relevant transcription factor binding sites. Importantly, diverged regulatory elements are associated with key genes required for normal limb patterning or normal eye development and function, suggesting that regulatory divergence contributed to the loss of these phenotypes. Together, our results provide the first evidence that genome-wide decay of the phenotype-specific cis-regulatory landscape is a hallmark of lost morphological traits.

genomics↗

bioRxiv2014

A Distance Method to Reconstruct Species Trees In the Presence of Gene Flow

One of the central tasks in evolutionary biology is to reconstruct the evolutionary relationships among species from sequence data, particularly from multilocus data. In the last ten years, many methods have been proposed to use the variance in the gene histories to estimate species trees by explicitly modeling deep coalescence. However, gene flow, another process that may produce gene history variance, has been less studied. In this paper, we propose a simple yet innovative method for species trees estimation in the presence of gene flow. Our method, called STEST (Species Tree Estimation from Speciation Times), constructs species tree estimates from pairwise speciation time or species divergence time estimates. By using methods that estimate speciation times in the presence of gene flow, (for example, M1 (Yang 2010) or SIM3s (Zhu and Yang 2012)), STEST is able to estimate species trees from data subject to gene flow. We develop two methods, called STEST (M1) and STEST (SIM3s), for this purpose. Additionally, we consider the method STEST (M0), which instead uses the M0 method (Yang 2002), a coalescent-based method that does not assume gene flow, to estimate speciation times. It is therefore devised to estimate species trees in the absence of gene flow. Our simulation studies show that STEST (M0) outperforms STEST(M1), STEST (SIM3s) and STEM in terms of estimation accuracy and outperfroms *BEAST in terms of running time when the degree of gene flow is small. STEST (M1) outperforms STEST (M0), STEST (SIM3s), STEM and *BEAST in term of estimation accuracy when the degree of gene flow is large. An empirical data set analyzed by these methods gives species tree estimates that are consistent with the previous results.

Evolutionary Biology↗

bioRxiv2017

Stochastic character mapping of state-dependent diversification reveals the tempo of evolutionary decline in self-compatible lineages

A major goal of evolutionary biology is to identify key evolutionary transitions that correspond with shifts in speciation and extinction rates. Stochastic character mapping has become the primary method used to infer the timing, nature, and number of character state transitions along the branches of a phylogeny. The method is widely employed for standard substitution models of character evolution. However, current approaches cannot be used for models that specifically test the association of character state transitions with shifts in diversification rates such as state-dependent speciation and extinction (SSE) models. Here we introduce a new stochastic character mapping algorithm that overcomes these limitations, and apply it to study mating system evolution over a time-calibrated phylogeny of the plant family Onagraceae. Utilizing a hidden state SSE model we tested the association of the loss of self-incompatibility with shifts in diversification rates. We found that self-compatible lineages have higher extinction rates and lower net-diversification rates compared to self-incompatible lineages. Furthermore, these results provide empirical evidence for the \"senescing\" diversification rates predicted in highly selfing lineages: our mapped character histories show that the loss of self-incompatibility is followed by a short-term spike in speciation rates, which declines after a time lag of several million years resulting in negative net-diversification. Lineages that have long been self-compatible, such as Fuchsia and Clarkia, are in a previously unrecognized and ongoing evolutionary decline. Our results demonstrate that stochastic character mapping of SSE models is a powerful tool for examining the timing and nature of both character state transitions and shifts in diversification rates over the phylogeny.

evolutionary biology↗

bioRxiv2018

Genome-wide disruption of DNA methylation by 5-aza-2’-deoxycytidine in the parasitioid wasp Nasonia vitripennis

DNA methylation of cytosine residues across the genome influences how genes and phenotypes are regulated in a wide range of organisms. As such, understanding the role of DNA methylation and other epigenetic mechanisms has become very much a part of mapping genotype to phenotype, a major question in evolutionary biology. Ideally, we would like to manipulate DNA methylation patterns on a genome-wide scale, to help us to elucidate the role that epigenetic modifications play in phenotypic expression. Recently, the demethylating agent 5-aza-2-deoxycytidine (5-aza-dC; commonly used in the epigenetic treatment of certain cancers), has been deployed to explore the epigenetic regulation of a number of traits of interest to evolutionary ecologists, including facultative sex allocation in the parasitoid wasp Nasonia vitripennis. In a recent study, we showed that treatment with 5-aza-dC did not ablate the facultative sex allocation response in Nasonia, but shifted the patterns of sex allocation in a way predicted by genomic conflict theory. This was the first (albeit indirect) experimental evidence for genomic conflict over sex allocation facilitated by DNA methylation. However, that work lacked direct evidence of the effects of 5-aza-dC on DNA methylation, and indeed the effect of the chemical has since been questioned in Nasonia. Here, using whole-genome bisulphite sequencing of more than 4 million CpGs, across more than 11,000 genes, we demonstrate unequivocally that 5-aza-dC disrupts methylation on a large scale across the Nasonia vitripennis genome. We show that the disruption can lead to both hypo- and hyper-methylation, may vary across tissues and time of sampling, and that the effects of 5-aza-dC are context- and sequence specific. We conclude that 5-aza-dC does indeed have the potential to be repurposed as a tool for studying the role of DNA methylation in evolutionary ecology, whilst many details of its action remain to be discovered. Author SummaryShedding light on the mechanistic basis of phenotypes is a major aim in the field of evolutionary biology. If we understand how phenotypes are controlled at the molecular level, we can begin to understand how evolution has shaped that phenotype and conversely, how genetic architecture may constrain trait evolution. Epigenetic markers (such as DNA methylation) also influence phenotypic expression by regulating how and when genes are expressed. Recently, 5-aza-2-deoxycytidine (5-aza-dC), a hypomethylating agent used in the treatment of certain cancers, has been used to explore the epigenetic regulation of traits of interest to evolutionary ecologists. Previously, we used 5-aza-dC to validate a role for DNA methylation in facultative sex allocation behaviour in the parasitoid wasp Nasonia vitripennis. However, the direct effects of the chemical were not examined at that point and its efficacy in insects was questioned. Here, we demonstrate that 5-aza-dC disrupts DNA methylation on a genome-wide scale in a context- and sequence-specific manner and results in both hypo- and hyper-methylation. Our work demonstrates that 5-aza-dC has the potential to be repurposed as a tool for studying the role of DNA methylation in phenotypic expression.

evolutionary biology↗

bioRxiv2018

Genotypic context modulates fitness landscapes: Effects onthe speed and direction of evolution for antimicrobialresistance

Understanding the forces that drive the dynamics of adaptive evolution is a goal of many subfields within evolutionary biology. The fitness landscape analogy has served as a useful abstraction for addressing these topics across many systems, and recent treatments have revealed how different environments can frame the particulars of adaptive evolution by changing the topography of fitness landscapes. In this study, we examine how the larger, ambient genotypic context in which the fitness landscape being modeled is embedded affects fitness landscape topography and subsequent evolution. Using simulations on empirical fitness landscapes, we discover that genotypic context, defined by genetic variability in regions outside of the locus under study (in this case, an essential bacterial enzyme target of antibiotics), influences the speed and direction of evolution in several surprising ways. These findings have implications for how we study the evolution of drug resistance in nature, and for presumptions about how biological evolution might be expected to occur in genetically-modified organisms. More generally, the findings speak to theory surrounding how \"difference can beget difference\" in adaptive evolution: that small genetic differences between organisms can greatly alter the specifics of how evolution occurs, which can rapidly drive even slightly diverged populations further apart.\n\nAuthor summaryTechnological advances enable scientists to engineer individual mutations at specific sites within an organisms genome with increasing ease. These breakthroughs have provided scientists with tools to study how different engineered mutations affect the function of a given gene or protein, yielding useful insight into genotype-phenotype mapping and evolution. In this study, we use engineered strains of bacteria to show how the dynamics (speed and direction) of evolution of drug resistance in an enzyme depends on the species-type of that bacterial enzyme, and on the presence/absence of mutations in other genes in the bacterial genome. These findings have broad implications for public health, genetic engineering, and theories of speciation. In the context of public health and biomedicine, our results suggest that future efforts in managing antimicrobial resistance must consider genetic makeup of different pathogen populations before predicting how resistance will occur, rather than assuming that the same resistance pathways will appear in different pathogen populations. With regard to broader theory in evolutionary biology, our results show how even small genetic differences between organisms can alter how future evolution occurs, potentially causing closely-related populations to quickly diverge.

evolutionary biology↗

bioRxiv2014

Bridging the Genotype and the Phenotype: Towards An Epigenetic Landscape Approach to Evolutionary Systems Biology

Understanding the mapping of genotypes into phenotypes is a central challenge of current biological research. Such mapping, conceptually represents a developmental mechanism through which phenotypic variation can be generated. Given the nongenetic character of developmental dynamics, phenotypic variation to a great extent has been neglected in the study of evolution. What is the relevance of considering this generative process in the study of evolution? How can we study its evolutionary consequences? Despite an historical systematic bias towards linear causation schemes in biology; in the post-genomic era, a systems-view to biology based on nonlinear (network) thinking is increasingly being adopted. Within this view, evolutionary dynamics can be studied using simple dynamical models of gene regulatory networks (GRNs). Through the study of GRN dynamics, genotypes and phenotypes can be unambiguously defined. The orchestrating role of GRNs constitutes an operational non-linear genotype-phenotype map. Further extension of these GRN models in order to explore and characterize an associated Epigenetic Landscape enables the study of the evolutionary consequences of both genetic and non-genetic sources of phenotypic variation within the same coherent theoretical framework. The merging of conceptually clear theories, computational/mathematical tools, and molecular/genomic data into coherent frameworks could be the basis for a transformation of biological research from mainly a descriptive exercise into a truly mechanistic, explanatory endeavor.

Systems Biology↗

bioRxiv2018

Evolutionary rate coevolution between mitochondria and mitochondria-associated nuclear-encoded proteins in insects

The mitochondrion is a pivotal organelle for energy production, and includes components encoded by both the mitochondrial and nuclear genomes. How these two genomes coevolve is a long-standing question in evolutionary biology. Here we initially investigate the evolutionary rates of mitochondrial components (oxidative phosphorylation (OXPHOS) proteins and ribosomal RNAs) and nuclear-encoded proteins associated with mitochondria, across the major orders of holometabolous insects. There are significant evolutionary rate correlations (ERCs) between mitochondria and mitochondria-associated nuclear-encoded proteins, which is likely driven by different rates of mitochondrial sequence evolution and compensatory changes in the interacting nuclear-encoded proteins. The pattern holds after correction for phylogenetic relationships and considering protein conservation levels. Correlations are stronger for nuclear-encoded OXPHOS proteins in contact with mitochondrial-encoded OXPHOS proteins and nuclear-encoded mitochondrial ribosomal amino acids directly contacting the mitochondrial rRNA. Mitochondrial-associated proteins show apparent rate acceleration over evolutionary time, but we suspect this pattern to be due to artifacts (e.g. rate estimation or calibration bias). We find that ERC between mitochondrial and nuclear proteins is a strong predictor of nuclear proteins known to interact with mitochondria, and therefore ERCs can be used to predict new candidate nuclear proteins with mitochondrial function. Using this approach, we detect proteins with high ERCs but not with known mitochondrial function based on gene ontology (GO). Manual screening of the literature revealed potential mitochondrial function for some of these proteins in humans or yeast. Their holometabolous ERCs therefore indicate these proteins may have phylogenetically conserved mitochondrial function. Twenty three additional candidates warrant further study for mitochondrial function based on this approach, including ERC evidence that proteins in the minichromosome maintenance helicase (MCM) complex interact with mitochondria. We conclude that the ERC method shows promise for identifying new candidate proteins with mitochondrial function.

evolutionary biology↗

bioRxiv2018

Two levels of host-specificity in a fig-associated Caenorhabditis

BackgroundBiotic interactions are ubiquitous and require information from ecology, evolutionary biology, and functional genetics in order to be completely understood. However, study systems that are amenable to investigations across such disparate fields are rare. Figs and fig wasps are a classic system for ecology and evolutionary biology with poor functional genetics; C. elegans is a classic system for functional genetics with poor ecology. In order to help bridge these disciplines, here we describe the natural history of a close relative of C. elegans, C. sp. 34, that is associated with the fig Ficus septica and its pollinating Ceratosolen wasps.\n\nResultsTo understand the natural context of fig-associated Caenorhabditis, fresh F. septica figs from four Okinawan islands were sampled, dissected, and observed under microscopy. C. sp. 34 was found in all islands where F. septica figs were found. C. sp. 34 was routinely found in the fig interior and almost never observed on the outside surface. Caenorhabditis was only found in pollinated figs, and C. sp. 34 was more likely to be observed in figs with more foundress pollinating wasps. Actively reproducing C. sp. 34 dominated younger figs, whereas older figs with emerging wasp progeny harbored C. sp. 34 dispersal larvae. Additionally, C. sp. 34 was observed dismounting from plated Ceratosolen pollinating wasps. C. sp. 34 was never found on non-pollinating, parasitic Philotrypesis wasps. Finally, C. sp. 34 was only observed in F. septica figs among five Okinawan Ficus species sampled.\n\nConclusionThese observations suggest a natural history where C. sp. 34 proliferates in young F. septica figs and disperses from old figs on Ceratosolen pollinating fig wasps. The fig and wasp host specificity of this Caenorhabditis is highly divergent from its close relatives and frames hypotheses for future investigations. This natural co-occurrence of the fig/fig wasp and Caenorhabditis study systems sets the stage for an integrated research program that can help to explain the evolution of interspecific interactions.

ecology↗

bioRxiv2016

Tradeoffs between microbial growth phases lead to frequency-dependent and non-transitive selection

Mutations in a microbial population can increase the frequency of a genotype not only by increasing its exponential growth rate, but also by decreasing its lag time or adjusting the yield (resource efficiency). The contribution of multiple life-history traits to selection is a critical question for evolutionary biology as we seek to predict the evolutionary fates of mutations. Here we use a model of microbial growth to show there are two distinct components of selection corresponding to the growth and lag phases, while the yield modulates their relative importance. The model predicts rich population dynamics when there are tradeo[ff]s between phases: multiple strains can coexist or exhibit bistability due to frequency-dependent selection, and strains can engage in rock-paper-scissors interactions due to non-transitive selection. We characterize the environmental conditions and patterns of traits necessary to realize these phenomena, which we show to be readily accessible to experiments. Our results provide a theoretical framework for analyzing high-throughput measurements of microbial growth traits, especially interpreting the pleiotropy and correlations between traits across mutants. This work also highlights the need for more comprehensive measurements of selection in simple microbial systems, where the concept of an ordinary fitness landscape breaks down.

evolutionary biology↗

bioRxiv2018

Untangling the role of selection and drift in population divergence via transcriptional network simulations: Extended analysis of Ghalambor et al. (2015)

Introduction Introduction Literature Cited A long-standing question in evolutionary biology is whether phenotypic plasticity influences adaptive evolutionary change (e.g. Waddington 1961; Price et al. 2003; Ghalambor et al. 2007; Lande 2009; Wund 2012). The same genotype can produce different phenotypes in response to different environments, but whether such plasticity constrains or facilitates evolutionary change remains an unresolved and controversial problem (Ghalambor et al. 2007). Theoretical models to date have made diverse predictions on the role of plasticity in evolutionary divergence (e.g. Ancel 2000; Paenke et al. 2007; Thibert-Plante and Hendry 2011), and empirical studies have largely been limited to retrospective approaches that infer the role of plasticity long-after popu ...

evolutionary biology↗

bioRxiv2018

Sequence variation of rare outer membrane protein β-barrel domains in clinical strains provides insights into the evolution of Treponema pallidum subsp. pallidum, the syphilis spirochete.

In recent years, considerable progress has been made in topologically and functionally characterizing integral outer membrane proteins (OMPs) of Treponema pallidum subspecies pallidum (TPA), the syphilis spirochete, and identifying its surface-exposed {beta}-barrel domains. Extracellular loops in OMPs of Gram-negative bacteria are known to be highly variable. We examined the sequence diversity of {beta}-barrel-encoding regions of tprC, tprD, and bamA, in 31 specimens from Cali, Colombia; San Francisco, California; and the Czech Republic and compared them to allelic variants in the 41 reference genomes in the NCBI database. To establish a phylogenetic framework, we used tp0548 genotyping and tp0558 sequences to assign strains to the Nichols or SS14 clades. We found that (i) {beta}-barrels in clinical strains could be grouped according to allelic variants in TPA reference genomes; (ii) for all three OMP loci, clinical strains within the Nichols or SS14 clades often harbored {beta}-barrel variants that differed from the Nichols and SS14 reference strains; and (iii) OMP variable regions often reside in predicted extracellular loops containing B-cell epitopes. Based upon structural models, non-conservative amino acid substitutions in predicted transmembrane {beta}-strands of TprC and TprD2 could give rise to functional differences in their porin channels. OMP profiles of some clinical strains were mosaics of different reference strains and did not correlate with results from enhanced molecular typing. Our observations suggest that human host selection pressures drive TPA OMP diversity and that genetic exchange contributes to the evolutionary biology of TPA. They also set the stage for topology-based analysis of antibody responses against OMPs and help frame strategies for syphilis vaccine development.\n\nIMPORTANCEDespite recent progress characterizing outer membrane proteins (OMPs) of Treponema pallidum (TPA), little is known about how their surface-exposed, {beta}-barrel-forming domains vary among strains circulating within high-risk populations. In this study, sequences for the {beta}-barrel-encoding regions of three OMP loci, tprC, tprD, and bamA, in TPA from a large number of patient specimens from geographically disparate sites were examined. Structural models predict that sequence variation within {beta}-barrel domains occurred predominantly within predicted extracellular loops. Amino acid substitutions in predicted transmembrane strands that could potentially affect porin channel function also were noted. Our findings suggest that selection pressures exerted by human populations drive TPA OMP diversity and that recombination at OMP loci contributes to the evolutionary biology of syphilis spirochetes. These results also set the stage for topology-based analysis of antibody responses that promote clearance of TPA and frame strategies for vaccine development based upon conserved OMP extracellular loops.

microbiology↗

bioRxiv2015

Extensive de novo mutation rate variation between individuals and across the genome of Chlamydomonas reinhardtii

Describing the process of spontaneous mutation is fundamental for understanding the genetic basis of disease, the threat posed by declining population size in conservation biology, and in much evolutionary biology. However, directly studying spontaneous mutation is difficult because of the rarity of de novo mutations. Mutation accumulation (MA) experiments overcome this by allowing mutations to build up over many generations in the near absence of natural selection. In this study, we sequenced the genomes of 85 MA lines derived from six genetically diverse wild strains of the green alga Chlamydomonas reinhardtii. We identified 6,843 spontaneous mutations, more than any other study of spontaneous mutation. We observed seven-fold variation in the mutation rate among strains and that mutator genotypes arose, increasing the mutation rate dramatically in some replicates. We also found evidence for fine-scale heterogeneity in the mutation rate, driven largely by the sequence flanking mutated sites, and by clusters of multiple mutations at closely linked sites. There was little evidence, however, for mutation rate heterogeneity between chromosomes or over large genomic regions of 200Kbp. Using logistic regression, we generated a predictive model of the mutability of sites based on their genomic properties, including local GC content, gene expression level and local sequence context. Our model accurately predicted the average mutation rate and natural levels of genetic diversity of sites across the genome. Notably, trinucleotides vary 17-fold in rate between the most mutable and least mutable sites. Our results uncover a rich heterogeneity in the process of spontaneous mutation both among individuals and across the genome.

Genomics↗