Tree House Explorer: A Novel Genome Browser for Phylogenomics

Tree House Explorer (THEx) is a genome browser that integrates phylogenomic data and genomic annotations into a single interactive platform for combined analysis. THEx allows users to visualize genome-wide variation in evolutionary histories and genetic divergence on a chromosome-by-chromosome basis, with continuous sliding window comparisons to gene annotations, recombination rates, and other user-specified, highly customizable feature annotations. THEx provides a new platform for interactive phylogenomic data visualization to analyze and interpret the diverse evolutionary histories woven throughout genomes. Hosted on Conda, THEx integrates seamlessly into new or pre-existing workflows.     

Quantifying selection acting on a complex trait using allele frequency time series data

When selection is acting on a large genetically diverse population, beneficial alleles increase in frequency. This fact can be used to map quantitative trait loci by sequencing the pooled DNA from the population at consecutive time points and observing allele frequency changes. Here, we present a population genetic method to analyze time series data of allele frequencies from such an experiment. Beginning with a range of proposed evolutionary scenarios, the method measures the consistency of each with the observed frequency changes. Evolutionary theory is utilized to formulate equations of motion for the allele frequencies, following which likelihoods for having observed the sequencing data under each scenario are derived. Comparison of these likelihoods gives an insight into the prevailing dynamics of the system under study. We illustrate the method by quantifying selective effects from an experiment, in which two phenotypically different yeast strains were first crossed and then propagated under heat stress (Parts L, Cubillos FA, Warringer J, et al. [14 co-authors]. 2011. Revealing the genetic structure of a trait by sequencing a population under selection. Genome Res). From these data, we discover that about 6% of polymorphic sites evolve nonneutrally under heat stress conditions, either because of their linkage to beneficial (driver) alleles or because they are drivers themselves. We further identify 44 genomic regions containing one or more candidate driver alleles, quantify their apparent selective advantage, obtain estimates of recombination rates within the regions, and show that the dynamics of the drivers display a strong signature of selection going beyond additive models. Our approach is applicable to study adaptation in a range of systems under different evolutionary pressures.     

Optimal Strategy for Competence Differentiation in Bacteria

A phylogenetically diverse subset of bacterial species are naturally competent for transformation by DNA. Transformation entails recombination of genes between different lineages, representing a form of bacterial sex that increases standing genetic variation. We first assess whether homologous recombination by transformation is favored by evolution. Using stochastic population genetic computer simulations in which beneficial and deleterious mutations occur at many loci throughout the whole genome, we find that transformation can increase both the rate of adaptive evolution and the equilibrium level of fitness. Secondly, motivated by experimental observations of Bacillus subtilis, we assume that competence additionally entails a weak persister phenotype, i.e., the rates of birth and death are reduced for these cells. Consequently, persisters evolve more slowly than non-persisters. We show via simulation that strains which stochastically switch into and out of the competent phenotype are evolutionarily favored over strains that express only a single phenotype. Our model''s simplicity enables us to derive and numerically solve a system of finite- deterministic equations that describe the evolutionary dynamics. The observed tradeoff between the benefit of recombination and the cost of persistence may explain the previously mysterious observation that only a fractional subpopulation of B. subtilis cells express competence. More generally, this work demonstrates that population genetic forces can give rise to phenotypic diversity even in an unchanging and homogeneous environment.     

Gene conversion and the evolution of three leucine-rich repeat gene families in Arabidopsis thaliana

The high number of duplicated genes in plant genomes provides a potential template for gene conversion and unequal crossing-over. Within a gene family these two processes can render all members homogeneous or generate diversity by reassorting variants among paralogs. The latter is especially feasible in families where gene diversity confers a selective advantage and thus conversion events are likely to be retained. Consequently, the most complete record of gene conversion is expected to be most evident in gene families commonly subjected to positive selection. Here, we describe the extent and characteristics of gene conversion and unequal crossing-over in the coding and noncoding regions of nucleotide-binding site leucine-rich repeat (NBS-LRR), receptor-like kinases (RLK), and receptor-like proteins (RLP) in the plant Arabidopsis thaliana. Members of these three gene families are associated with disease resistance and their pathogen-recognition domain is a documented target of positive selection. Our bioinformatic approach to study the major family features that may influence gene conversion revealed that in these families there is a significant association between the occurrence of gene conversion and high levels of sequence similarity, close physical clustering, gene orientation, and recombination rate. We discuss these results in the context of the overlap between gene conversion and positive selection during the evolutionary expansion of the NBS-LRR, RLK, and RLP gene families.     

Geonomics: Forward-Time,Spatially Explicit,and Arbitrarily Complex Landscape Genomic Simulations

Understanding the drivers of spatial patterns of genomic diversity has emerged as a major goal of evolutionary genetics. The flexibility of forward-time simulation makes it especially valuable for these efforts, allowing for the simulation of arbitrarily complex scenarios in a way that mimics how real populations evolve. Here, we present Geonomics, a Python package for performing complex, spatially explicit, landscape genomic simulations with full spatial pedigrees that dramatically reduces user workload yet remains customizable and extensible because it is embedded within a popular, general-purpose language. We show that Geonomics results are consistent with expectations for a variety of validation tests based on classic models in population genetics and then demonstrate its utility and flexibility with a trio of more complex simulation scenarios that feature polygenic selection, selection on multiple traits, simulation on complex landscapes, and nonstationary environmental change. We then discuss runtime, which is primarily sensitive to landscape raster size, memory usage, which is primarily sensitive to maximum population size and recombination rate, and other caveats related to the model’s methods for approximating recombination and movement. Taken together, our tests and demonstrations show that Geonomics provides an efficient and robust platform for population genomic simulations that capture complex spatial and evolutionary dynamics.     

Climate change effects on animal and plant phylogenetic diversity in southern Africa

Much attention has been paid to the effects of climate change on species' range reductions and extinctions. There is however surprisingly little information on how climate change driven threat may impact the tree of life and result in loss of phylogenetic diversity (PD). Some plant families and mammalian orders reveal nonrandom extinction patterns, but many other plant families do not. Do these discrepancies reflect different speciation histories and does climate induced extinction result in the same discrepancies among different groups? Answers to these questions require representative taxon sampling. Here, we combine phylogenetic analyses, species distribution modeling, and climate change projections on two of the largest plant families in the Cape Floristic Region (Proteaceae and Restionaceae), as well as the second most diverse mammalian order in Southern Africa (Chiroptera), and an herbivorous insect genus (Platypleura) in the family Cicadidae to answer this question. We model current and future species distributions to assess species threat levels over the next 70 years, and then compare projected with random PD survival. Results for these animal and plant clades reveal congruence. PD losses are not significantly higher under predicted extinction than under random extinction simulations. So far the evidence suggests that focusing resources on climate threatened species alone may not result in disproportionate benefits for the preservation of evolutionary history.     

Distribution of cp32 Prophages among Lyme Disease-Causing Spirochetes and Natural Diversity of Their Lipoprotein-Encoding erp Loci

Lyme disease spirochetes possess complex genomes, consisting of a main chromosome and 20 or more smaller replicons. Among those small DNAs are the cp32 elements, a family of prophages that replicate as circular episomes. All complete cp32s contain an erp locus, which encodes surface-exposed proteins. Sequences were compared for all 193 erp alleles carried by 22 different strains of Lyme disease-causing spirochete to investigate their natural diversity and evolutionary histories. These included multiple isolates from a focus where Lyme disease is endemic in the northeastern United States and isolates from across North America and Europe. Bacteria were derived from diseased humans and from vector ticks and included members of 5 different Borrelia genospecies. All erp operon 5′-noncoding regions were found to be highly conserved, as were the initial 70 to 80 bp of all erp open reading frames, traits indicative of a common evolutionary origin. However, the majority of the protein-coding regions are highly diverse, due to numerous intra- and intergenic recombination events. Most erp alleles are chimeras derived from sequences of closely related and distantly related erp sequences and from unknown origins. Since known functions of Erp surface proteins involve interactions with various host tissue components, this diversity may reflect both their multiple functions and the abilities of Lyme disease-causing spirochetes to successfully infect a wide variety of vertebrate host species.     

Evolutionary Dynamics of Ralstonia solanacearum

We investigated the genetic diversity, extent of recombination, natural selection, and population divergence of Ralstonia solanacearum samples obtained from sources worldwide. This plant pathogen causes bacterial wilt in many crops and constitutes a serious threat to agricultural production due to its very wide host range and aggressiveness. Five housekeeping genes, dispersed around the chromosome, and three virulence-related genes, located on the megaplasmid, were sequenced from 58 strains belonging to the four major phylogenetic clusters (phylotypes). Whereas genetic variation is high and consistent for all housekeeping loci studied, virulence-related gene sequences are more diverse. Phylogenetic and statistical analyses suggest that this organism is a highly diverse bacterial species containing four major, deeply separated evolutionary lineages (phylotypes I to IV) and a weaker subdivision of phylotype II into two subgroups. Analysis of molecular variations showed that the geographic isolation and spatial distance have been the significant determinants of genetic variation between phylotypes. R. solanacearum displays high clonality for housekeeping genes in all phylotypes (except phylotype III) and significant levels of recombination for the virulence-related egl and hrpB genes, which are limited mainly to phylotype strains III and IV. Finally, genes essential for species survival are under purifying selection, and those directly involved in pathogenesis might be under diversifying selection.     

Assessing the suitability of genetic diversity of Chironomus riparius (Meigen) as an indicator of environmental pollution

Reliable and cost-effective indicators are needed to reduce uncertainty in ecological risk assessments of chemicals so that their long-term and evolutionary impacts in the dynamics of stressed biological communities can be accounted for.In the present study we investigate the suitability of genetic diversity as an indicator of ecological disturbance of freshwater ecosystems. For that, we selected three freshwater systems with well-known histories of metal contamination and three nearby reference sites located in Northern Portugal and the effects of metal contamination were assessed both in the levels of genetic diversity of the non-biting midge Chironomus riparius Meigen (at microsatellite markers) and in the diversity and composition of the benthic macroinvertebrate communities.Results showed a remarkable impoverishment in the abundance and diversity of macroinvertebrate communities of metal polluted sites in which most sensitive taxa were eliminated and replaced by more opportunistic ones belonging mainly to Oligochaeta and Diptera. In contrast, no evidence for pollution-induced genetic erosion was found in C. riparius populations in the studied area, with genetic diversity of the species being indeed higher in sites with impoverished macroinvertebrate communities and poor habitat quality.Our findings suggest that there are important limitations to the use of measures of genetic diversity of C. riparius per se to unravel ecological disturbance. Field studies aiming at quantifying pollutant-driven genetic erosion need to carefully consider the ecological and demographic aspects of potential target species.     

Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals

Founder events play a critical role in shaping genetic diversity, fitness and disease risk in a population. Yet our understanding of the prevalence and distribution of founder events in humans and other species remains incomplete, as most existing methods require large sample sizes or phased genomes. Thus, we developed ASCEND that measures the correlation in allele sharing between pairs of individuals across the genome to infer the age and strength of founder events. We show that ASCEND can reliably estimate the parameters of founder events under a range of demographic scenarios. We then apply ASCEND to two species with contrasting evolutionary histories: ~460 worldwide human populations and ~40 modern dog breeds. In humans, we find that over half of the analyzed populations have evidence for recent founder events, associated with geographic isolation, modes of sustenance, or cultural practices such as endogamy. Notably, island populations have lower population sizes than continental groups and most hunter-gatherer, nomadic and indigenous groups have evidence of recent founder events. Many present-day groups––including Native Americans, Oceanians and South Asians––have experienced more extreme founder events than Ashkenazi Jews who have high rates of recessive diseases due their known history of founder events. Using ancient genomes, we show that the strength of founder events differs markedly across geographic regions and time––with three major founder events related to the peopling of Americas and a trend in decreasing strength of founder events in Europe following the Neolithic transition and steppe migrations. In dogs, we estimate extreme founder events in most breeds that occurred in the last 25 generations, concordant with the establishment of many dog breeds during the Victorian times. Our analysis highlights a widespread history of founder events in humans and dogs and elucidates some of the demographic and cultural practices related to these events.     

Multidimensional Epistasis and the Transitory Advantage of Sex

Identifying and quantifying the benefits of sex and recombination is a long-standing problem in evolutionary theory. In particular, contradictory claims have been made about the existence of a benefit of recombination on high dimensional fitness landscapes in the presence of sign epistasis. Here we present a comparative numerical study of sexual and asexual evolutionary dynamics of haploids on tunably rugged model landscapes under strong selection, paying special attention to the temporal development of the evolutionary advantage of recombination and the link between population diversity and the rate of adaptation. We show that the adaptive advantage of recombination on static rugged landscapes is strictly transitory. At early times, an advantage of recombination arises through the possibility to combine individually occurring beneficial mutations, but this effect is reversed at longer times by the much more efficient trapping of recombining populations at local fitness peaks. These findings are explained by means of well-established results for a setup with only two loci. In accordance with the Red Queen hypothesis the transitory advantage can be prolonged indefinitely in fluctuating environments, and it is maximal when the environment fluctuates on the same time scale on which trapping at local optima typically occurs.     

Perspectives of genomic diversification and molecular recombination towards R-gene evolution in plants

Plants are under strong evolutionary pressure in developing new and noble R genes to recognize pathogen avirulence (avr) determinants and bring about stable defense for generation after generations. Duplication, sequence variation by mutation, disparity in the length and structure of leucine rich repeats etc., causes tremendous variations within and among R genes in a plant thereby developing diverse recognitional specificity suitable enough for defense against new pathogens. Recent studies on genome sequencing, diversity and population genetics in different plants have thrown new insights on the molecular evolution of these genes. Tandem and segmental duplication are important factors in R gene abundance as inferred from the distribution of major nucleotide binding site-leucine rich repeats (NBS-LRRs) type R-genes in plant genomes. Likewise, R-gene evolution is also thought to be facilitated by cluster formation thereby causing recombination and sequence exchange and resulting in haplotypic diversity. Population studies have further proven that balancing selection is responsible for the maintenance of allelic diversity in R genes. In this review, we emphasize and discuss on improved perspectives towards the molecular mechanisms and selection pressure responsible for the evolution of NBS-LRR class resistance genes in plants.     

Diversity of Prdm9 Zinc Finger Array in Wild Mice Unravels New Facets of the Evolutionary Turnover of this Coding Minisatellite

In humans and mice, meiotic recombination events cluster into narrow hotspots whose genomic positions are defined by the PRDM9 protein via its DNA binding domain constituted of an array of zinc fingers (ZnFs). High polymorphism and rapid divergence of the Prdm9 gene ZnF domain appear to involve positive selection at DNA-recognition amino-acid positions, but the nature of the underlying evolutionary pressures remains a puzzle. Here we explore the variability of the Prdm9 ZnF array in wild mice, and uncovered a high allelic diversity of both ZnF copy number and identity with the caracterization of 113 alleles. We analyze features of the diversity of ZnF identity which is mostly due to non-synonymous changes at codons −1, 3 and 6 of each ZnF, corresponding to amino-acids involved in DNA binding. Using methods adapted to the minisatellite structure of the ZnF array, we infer a phylogenetic tree of these alleles. We find the sister species Mus spicilegus and M. macedonicus as well as the three house mouse (Mus musculus) subspecies to be polyphyletic. However some sublineages have expanded independently in Mus musculus musculus and M. m. domesticus, the latter further showing phylogeographic substructure. Compared to random genomic regions and non-coding minisatellites, none of these patterns appears exceptional. In silico prediction of DNA binding sites for each allele, overlap of their alignments to the genome and relative coverage of the different families of interspersed repeated elements suggest a large diversity between PRDM9 variants with a potential for highly divergent distributions of recombination events in the genome with little correlation to evolutionary distance. By compiling PRDM9 ZnF protein sequences in Primates, Muridae and Equids, we find different diversity patterns among the three amino-acids most critical for the DNA-recognition function, suggesting different diversification timescales.     

Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction

Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx) genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host-virus interactions and species-specific susceptibility to viral infection.     

Chromosome organization and gene expansion in the highly fragmented genome of the ciliate Strombidium stylifer

Chromosomes are well-organized carriers of genetic information in eukaryotes and are usually quite long, carrying hundreds and thousands of genes. Intriguingly, a clade of single-celled ciliates, Spirotrichea, feature nanochromosomes—also called “gene-sized chromosomes”. These chromosomes predominantly carry only one gene, flanked by short telomere sequences. However, the organization and copy number variation of the chromosomes in these highly fragmented genomes remain unexplored in many groups of Spirotrichea, including the marine Strombidium. Using deep genome sequencing, we assembled the macronuclear genome of Strombidium stylifer into more than 18,000 nanochromosomes (~2.4 Kb long on average). Our results show that S. stylifer occupies an intermediate position during the evolutionary history of Strombidium lineage and experienced significant expansions in several gene families related to guanyl ribonucleotide binding. Based on the nucleotide distribution bias analysis and conserved motifs search in non-genic regions, we found that the subtelomeric regions have a conserved adenine-thymine (AT)-rich sequence motif. We also found that the copy number of nanochromosomes lacks precise regulation. This work sheds light on the unique features of chromosome structure in eukaryotes with highly fragmented genomes and reveals that a rather specialized evolutionary strategy at the genomic level has resulted in great diversity within the ciliated lineages.     

Post-genomic science: converting primary structure into physiological function

Exobiology, the study of the origin, evolution and distribution of life (including life on earth) within the context of cosmic evolution, is being given a remarkable boost by genome sequencing projects, which are now making the evolutionary histories of protein families routinely available. These histories comprise a multiple alignment for their protein sequences and the corresponding DNA sequences, an evolutionary tree showing the pedigree of these sequences, and reconstructed ancestral sequences for each node in the tree. In a post-genomic world having genomic sequences from an unlimited number of organisms, these histories will be used to connect structure, chemical reactivity, and physiological function to these families. This paper describes several “post-genomic” tools that exploit these evolutionary histories. They can be used to confirm or deny long distance homology between two protein families, identify proteins within a family that have new functions, and identify specific in vitro properties of the protein that are important for its physiological role. Evolution-based data structures for organizing large sequence databases are also described.     

Generalized linear mixed model for segregation distortion analysis

Background

Concerted evolution refers to the pattern in which copies of multigene families show high intraspecific sequence homogeneity but high interspecific sequence diversity. Sequence homogeneity of these copies depends on relative rates of mutation and recombination, including gene conversion and unequal crossing over, between misaligned copies. The internally repetitive intergenic spacer (IGS) is located between the genes for the 28S and 18S ribosomal RNAs. To identify patterns of recombination and/or homogenization within IGS repeat arrays, and to identify regions of the IGS that are under functional constraint, we analyzed 13 complete IGS sequences from 10 individuals representing four species in the Daphnia pulex complex.

Results

Gene conversion and unequal crossing over between misaligned IGS repeats generates variation in copy number between arrays, as has been observed in previous studies. Moreover, terminal repeats are rarely involved in these events. Despite the occurrence of recombination, orthologous repeats in different species are more similar to one another than are paralogous repeats within species that diverged less than 4 million years ago. Patterns consistent with concerted evolution of these repeats were observed between species that diverged 8-10 million years ago. Sequence homogeneity varies along the IGS; the most homogeneous regions are downstream of the 28S rRNA gene and in the region containing the core promoter. The inadvertent inclusion of interspecific hybrids in our analysis uncovered evidence of both inter- and intrachromosomal recombination in the nonrepetitive regions of the IGS.

Conclusions

Our analysis of variation in ribosomal IGS from Daphnia shows that levels of homogeneity within and between species result from the interaction between rates of recombination and selective constraint. Consequently, different regions of the IGS are on substantially different evolutionary trajectories.     

Analysis of distribution indicates diverse functions of simple sequence repeats in Mycoplasma genomes

Simple sequence repeats (SSRs) composed of extensive tandem iterations of a single nucleotide or a short oligonucleotide are rare in most bacterial genomes, but they are common among Mycoplasma. Some of these repeats act as contingency loci in association with families of surface antigens. By contraction or expansion during replication, these SSRs increase genetic variance of the population and facilitate avoidance of the immune response of the host. Occurrence and distribution of SSRs are analyzed in complete genomes of 11 Mycoplasma and 3 related Mollicutes in order to gain insights into functional and evolutionary diversity of the SSRs in Mycoplasma. The results revealed an unexpected variety of SSRs with respect to their distribution and composition and suggest that it is unlikely that all SSRs function as contingency loci or recombination hot spots. Various types of SSRs are most abundant in Mycoplasma hyopneumoniae, whereas Mycoplasma penetrans, Mycoplasma mobile, and Mycoplasma synoviae do not contain unusually long SSRs. Mycoplasma hyopneumoniae and Mycoplasma pulmonis feature abundant short adenine and thymine runs periodically spaced at 11 and 12 bp, respectively, which likely affect the supercoiling propensities of the DNA molecule. Physiological roles of long adenine and thymine runs in M. hyopneumoniae appear independent of location upstream or downstream of genes, unlike contingency loci that are typically located in protein-coding regions or upstream regulatory regions. Comparisons among 3 M. hyopneumoniae strains suggest that the adenine and thymine runs are rarely involved in genome rearrangements. The results indicate that the SSRs in the Mycoplasma genomes play diverse roles, including modulating gene expression as contingency loci, facilitating genome rearrangements via recombination, affecting protein structure and possibly protein-protein interactions, and contributing to the organization of the DNA molecule in the cell.     

Life history patterns shape energy allocation among fishes on coral reefs

Although critically important, the link between animal life histories and ecosystem energetics is seldom explored. In the pursuit of ecological simplification, ecosystem properties are typically described by models based on static counts, where organisms are aggregated into trophic- or size-based groups. Consequently, output is often based on an assumption that larger group biomass equals greater energetic contribution. Here, we modelled the individual growth of over 58,000 fishes from 74 genera within a coral reef ecosystem to investigate the role and importance of taxon-specific life histories to the division, spatial distribution and relative contribution of biomass production within 14 coral reef fish families. Rank changes among families in standing biomass to biomass production indicated that small cryptic families (e.g. Gobiidae and Blenniidae) exhibit collective growth potentials equal to or exceeding those of many other common families composed of individuals with body-sizes 1–3 orders of magnitude larger. Remaining at high risk of predation throughout their lives as a consequence of their small size, these cryptic fishes also provide a constant food resource and supply of reproductive energy to coral reefs throughout the year. Enhanced further by the strength and diversity of their trophic relationships within food webs, the highly productive nature of these small cryptic fishes suggests they make a substantial contribution to the flow of energy in coral reef ecosystems via predatory pathways. It appears that life histories leave a strong imprint on ecosystem energy fluxes and illustrate the importance of incorporating taxon-specific features when assigning values to key ecosystem processes. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.