CLARITY: comparing heterogeneous data using dissimilarity

Integrating datasets from different disciplines is hard because the data are often qualitatively different in meaning, scale and reliability. When two datasets describe the same entities, many scientific questions can be phrased around whether the (dis)similarities between entities are conserved across such different data. Our method, CLARITY, quantifies consistency across datasets, identifies where inconsistencies arise and aids in their interpretation. We illustrate this using three diverse comparisons: gene methylation versus expression, evolution of language sounds versus word use, and country-level economic metrics versus cultural beliefs. The non-parametric approach is robust to noise and differences in scaling, and makes only weak assumptions about how the data were generated. It operates by decomposing similarities into two components: a ‘structural’ component analogous to a clustering, and an underlying ‘relationship’ between those structures. This allows a ‘structural comparison’ between two similarity matrices using their predictability from ‘structure’. Significance is assessed with the help of re-sampling appropriate for each dataset. The software, CLARITY, is available as an R package from github.com/danjlawson/CLARITY .

High rates of evolution preceded shifts to sex-biased gene expression in Leucadendron, the most sexually dimorphic angiosperms

Differences between males and females are usually more subtle in dioecious plants than animals, but strong sexual dimorphism has evolved convergently in the South African Cape plant genus Leucadendron. Such sexual dimorphism in leaf size is expected largely to be due to differential gene expression between the sexes. We compared patterns of gene expression in leaves among ten Leucadendron species across the genus. Surprisingly, we found no positive association between sexual dimorphism in morphology and the number or the percentage of sex-biased genes. Sex bias in most sex-biased genes evolved recently and was species-specific. We compared rates of evolutionary change in expression for genes that were sex-biased in one species but unbiased in others and found that sex-biased genes evolved faster in expression than un-biased genes. This greater rate of expression evolution of sex-biased genes, also documented in animals, might suggest the possible role of sexual selection in the evolution of gene expression. However, our comparative analysis clearly indicates that the more rapid rate of expression evolution of sex-biased genes predated the origin of bias, and shifts towards bias were depleted in signatures of adaptation. Our results are thus more consistent with the view that sex bias is simply freer to evolve in genes less subject to constraints in expression level.

Parallel subgenome structure and divergent expression evolution of allo-tetraploid common carp and goldfish

How two subgenomes in allo-tetraploids adapt to coexistence and coordinate through structure and expression evolution requires extensive studies. In the present study, we report an improved genome assembly of allo-tetraploid common carp, an updated genome annotation of allo-tetraploid goldfish and the chromosome-scale assemblies of a progenitor-like diploid Puntius tetrazona and an outgroup diploid Paracanthobrama guichenoti. Parallel subgenome structure evolution in the allo-tetraploids was featured with equivalent chromosome components, higher protein identities, similar transposon divergence and contents, homoeologous exchanges, better synteny level, strong sequence compensation and symmetric purifying selection. Furthermore, we observed subgenome expression divergence processes in the allo-tetraploids, including inter-/intrasubgenome trans-splicing events, expression dominance, decreased expression levels, dosage compensation, stronger expression correlation, dynamic functionalization and balancing of differential expression. The potential disorders introduced by different progenitors in the allo-tetraploids were hypothesized to be alleviated by increasing structural homogeneity and performing versatile expression processes. Resequencing three common carp strains revealed two major ecotypes and uncovered candidate genes relevant to growth and survival rate.

Convergent patterns of gene expression and protein evolution associated with adaptation to desert environments in rodents

Desert specialization has arisen multiple times across rodents and is often associated with a suite of convergent phenotypes, including modification of the kidneys to mitigate water loss. However, the extent to which phenotypic convergence in desert rodents is mirrored at the molecular level is unknown. Here, we sequenced kidney mRNA and assembled transcriptomes for three pairs of rodent species to search for convergence in gene expression and amino acid sequence associated with adaptation to deserts. We conducted phylogenetically-independent comparisons between a desert specialist and a non-desert relative in three families representing ∼70 million years of evolution. Overall, patterns of gene expression faithfully recapitulated the phylogeny of these six taxa. However, we found that 8.6% of all genes showed convergent patterns of expression evolution between desert and non-desert taxa, a proportion that is much higher than expected by chance. In addition to these convergent changes, we observed many species-pair specific changes in gene expression indicating that different instances of adaptation to deserts include a combination of unique and shared changes. Patterns of protein evolution revealed a small number of genes showing evidence of positive selection, the majority of which did not show convergent changes in gene expression. Overall, our results suggest convergent changes in gene regulation play a primary role in the complex trait of desert adaptation in rodents.

No Expression Divergence despite Transcriptional Interference between Nested Protein-Coding Genes in Mammals

Nested protein-coding genes accumulated throughout metazoan evolution, with early analyses of human and Drosophila microarray data indicating that this phenomenon was simply due to the presence of large introns. However, a recent study employing RNA-seq data uncovered evidence of transcriptional interference driving rapid expression divergence between Drosophila nested genes, illustrating that accurate expression estimation of overlapping genes can enhance detection of their relationships. Hence, here I apply an analogous approach to strand-specific RNA-seq data from human and mouse to revisit the role of transcriptional interference in the evolution of mammalian nested genes. A genomic survey reveals that whereas mammalian nested genes indeed accrued over evolutionary time, they are retained at lower frequencies than in Drosophila. Though several properties of mammalian nested genes align with observations in Drosophila and with expectations under transcriptional interference, contrary to both, their expression divergence is not statistically different from that between unnested genes, and also does not increase after nesting. Together, these results support the hypothesis that lower selection efficiencies limit rates of gene expression evolution in mammals, leading to their reliance on immediate eradication of deleterious nested genes to avoid transcriptional interference.

The effects of introgression across thousands of quantitative traits revealed by gene expression in wild tomatoes

It is now understood that introgression can serve as powerful evolutionary force, providing genetic variation that can shape the course of trait evolution. Introgression also induces a shared evolutionary history that is not captured by the species phylogeny, potentially complicating evolutionary analyses that use a species tree. Such analyses are often carried out on gene expression data across species, where the measurement of thousands of trait values allows for powerful inferences while controlling for shared phylogeny. Here, we present a Brownian motion model for quantitative trait evolution under the multispecies network coalescent framework, demonstrating that introgression can generate apparently convergent patterns of evolution when averaged across thousands of quantitative traits. We test our theoretical predictions using whole-transcriptome expression data from ovules in the wild tomato genus Solanum. Examining two sub-clades that both have evidence for post speciation introgression, but that differ substantially in its magnitude, we find patterns of evolution that are consistent with histories of introgression in both the sign and magnitude of ovule gene expression. Additionally, in the sub-clade with a higher rate of introgression, we observe a correlation between local gene tree topology and expression similarity, implicating a role for introgressed cis-regulatory variation in generating these broad-scale patterns. Our results have important implications for the study of gene expression evolution, and quantitative trait evolution more broadly, in systems with evidence of introgression.

Tempo and mode of gene expression evolution in the brain across Primates

Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species 1,2. Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date e.g. 3,4. To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-Seq data from four brain regions in an unprecedented eighteen species. Here we show a remarkable level of variation in gene expression among hominid species, including humans and chimpanzees, despite their relatively recent divergence time from other primates. We found that individual genes display a wide range of expression dynamics across evolutionary time reflective of the diverse selection pressures acting on genes within primate brain tissue. Using our sample that represents an unprecedented 190-fold difference in primate brain size, we identified genes with variation in expression most correlated with brain size and found several with signals of positive selection in their regulatory regions. Our study extensively broadens the context of what is known about the molecular evolution of the brain across primates and identifies novel candidate genes for study of genetic regulation of brain development and evolution.

Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication

Background Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap, we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80–100 million years ago. Results We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards lower expression and possible pseudogenization. Loss of expression in one ohnolog is significantly associated with transposable element insertions in promoters and likely driven by selection on gene dosage including selection on stoichiometric balance. We also find symmetric expression shifts, and these are associated with genes under strong evolutionary constraints such as ribosome subunit genes. This possibly reflects selection operating to achieve a gene dose reduction while avoiding accumulation of “toxic mutations”. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one likely source of novel binding sites driving tissue-specific gains in expression. Conclusions Our results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.

Gene and Transposable Element Expression Evolution Following Recent and Past Polyploidy Events in Spartina (Poaceae)

Gene expression dynamics is a key component of polyploid evolution, varying in nature, intensity, and temporal scales, most particularly in allopolyploids, where two or more sub-genomes from differentiated parental species and different repeat contents are merged. Here, we investigated transcriptome evolution at different evolutionary time scales among tetraploid, hexaploid, and neododecaploid Spartina species (Poaceae, Chloridoideae) that successively diverged in the last 6–10 my, at the origin of differential phenotypic and ecological traits. Of particular interest are the recent (19th century) hybridizations between the two hexaploids Spartina alterniflora (2n = 6x = 62) and S. maritima (2n = 6x = 60) that resulted in two sterile F1 hybrids: Spartina × townsendii (2n = 6x = 62) in England and Spartina × neyrautii (2n = 6x = 62) in France. Whole genome duplication of S. × townsendii gave rise to the invasive neo-allododecaploid species Spartina anglica (2n = 12x = 124). New transcriptome assemblies and annotations for tetraploids and the enrichment of previously published reference transcriptomes for hexaploids and the allododecaploid allowed identifying 42,423 clusters of orthologs and distinguishing 21 transcribed transposable element (TE) lineages across the seven investigated Spartina species. In 4x and 6x mesopolyploids, gene and TE expression changes were consistent with phylogenetic relationships and divergence, revealing weak expression differences in the tetraploid sister species Spartina bakeri and Spartina versicolor (<2 my divergence time) compared to marked transcriptome divergence between the hexaploids S. alterniflora and S. maritima that diverged 2–4 mya. Differentially expressed genes were involved in glycolysis, post-transcriptional protein modifications, epidermis development, biosynthesis of carotenoids. Most detected TE lineages (except SINE elements) were found more expressed in hexaploids than in tetraploids, in line with their abundance in the corresponding genomes. Comparatively, an astonishing (52%) expression repatterning and deviation from parental additivity were observed following recent reticulate evolution (involving the F1 hybrids and the neo-allododecaploid S. anglica), with various patterns of biased homoeologous gene expression, including genes involved in epigenetic regulation. Downregulation of TEs was observed in both hybrids and accentuated in the neo-allopolyploid. Our results reinforce the view that allopolyploidy represents springboards to new regulatory patterns, offering to worldwide invasive species, such as S. anglica, the opportunity to colonize stressful and fluctuating environments on saltmarshes.