Expression Of Orthologous Genes Research Articles

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Tracing the evolutionary origin of chordate somites in the hemichordate Ptychodera flava.

Metameric somites are a novel character of chordates with unclear evolutionary origins. In the early branching chordate amphioxus, anterior somites are derived from the paraxial mesodermal cells that bud off the archenteron (i.e., enterocoely) at the end of gastrulation. Development of the anterior somites requires FGF signaling, and distinct somite compartments express orthologs of vertebrate non-axial mesodermal markers. Thus, it has been proposed that the amphioxus anterior somites are homologous to the vertebrate head mesoderm, paraxial mesoderm and lateral plate mesoderm. To trace the evolutionary origin of somites, it is essential to study the chordates' closest sister group, Ambulacraria, which includes hemichordates and echinoderms. The anterior coeloms of hemichordate and sea urchin embryos (respectively called protocoel and coelomic pouches) are also formed by enterocoely and require FGF signals for specification and/or differentiation. In this study, we applied RNA-seq to comprehensively screen for regulatory genes associated with the mesoderm-derived protocoel of the hemichordate Ptychodera flava. We also used a candidate gene approach to identify P. flava orthologs of chordate somite markers. In situ hybridization results showed that many of these candidate genes are expressed in distinct or overlapping regions of the protocoel, which indicates that molecular compartments exist in the hemichordate anterior coelom. Given that the hemichordate protocoel and amphioxus anterior somites share a similar ontogenic process (enterocoely), induction signal (FGF), and characteristic expression of orthologous genes, we propose that these two anterior coeloms are indeed homologous. In the lineage leading to the emergence of chordates, somites likely evolved from enterocoelic, FGF-dependent, and molecularly compartmentalized anterior coeloms of the deuterostome last common ancestor.

Sympatric Pieris butterfly species exhibit a high conservation of chemoreceptors.

Sensory processes have often been argued to play a central role in the selection of ecological niches and in the formation of new species. Butterflies are among the best studied animal groups with regards to their evolutionary and behavioral ecology and thereby offer an attractive system to investigate the role of chemosensory genes in sympatric speciation. We focus on two Pieris butterflies with overlapping host-plant ranges: P. brassicae and P. rapae. Host-plant choice in lepidopterans is largely based on their olfactory and gustatory senses. Although the chemosensory responses of the two species have been well characterized at the behavioral and physiological levels, little is known about their chemoreceptor genes. Here, we compared the chemosensory genes of P. brassicae and P. rapae to investigate whether differences in these genes might have contributed to their evolutionary separation. We identified a total of 130 and 122 chemoreceptor genes in the P. brassicae genome and antennal transcriptome, respectively. Similarly, 133 and 124 chemoreceptors were identified in the P. rapae genome and antennal transcriptome. We found some chemoreceptors being differentially expressed in the antennal transcriptomes of the two species. The motifs and gene structures of chemoreceptors were compared between the two species. We show that paralogs share conserved motifs and orthologs have similar gene structures. Our study therefore found surprisingly few differences in the numbers, sequence identities and gene structures between the two species, indicating that the ecological differences between these two butterflies might be more related to a quantitative shift in the expression of orthologous genes than to the evolution of novel receptors as has been found in other insects. Our molecular data supplement the wealth of behavioral and ecological studies on these two species and will thereby help to better understand the role of chemoreceptor genes in the evolution of lepidopterans.

Comparative immune-relevant transcriptome reveals the evolutionary basis of complex traits.

Comparing transcriptome can help us reveal the genetic and evolutionary architecture underlying complex phenotypes within and between species. Here, by analyzing 386 publicly available RNA sequencing samples using a uniform bioinformatics pipeline, we systematically compared expression profiles of 10 immune-relevant tissues across humans, mice, pigs, cattle, sheep, and chickens. In general, we demonstrated that gene expression of orthologous genes was conserved within tissues across species. By integrating our findings with results of genome-wide association studies (GWAS) from 17 health-relevant traits in humans and 16,539 health-relevant quantitative trait loci (QTLs) in animals, we found that transcriptionally conserved genes were significantly enriched for more heritability of complex traits, compared to species-specific genes. In conclusion, our results advanced the knowledge of the transcriptome evolution of immune tissues and demonstrated that multi-species transcriptome comparison is highly informative for understanding the genetics of complex traits/disease.

Dynamic Spatial-temporal Expression Ratio of X Chromosome to Autosomes but Stable Dosage Compensation in Mammals

In the evolutionary model of dosage compensation, per-allele expression level of the X chromosome has been proposed to have twofold up-regulation to compensate its dose reduction in males (XY) compared to females (XX). However, the expression regulation of X-linked genes is still controversial, and comprehensive evaluations are still lacking. By integrating multi-omics datasets in mammals, we investigated the expression ratios including X to autosomes (X:AA ratio) and X to orthologs (X:XX ratio) at the transcriptome, translatome, and proteome levels. We revealed a dynamic spatial-temporal X:AA ratio during development in humans and mice. Meanwhile, by tracing the evolution of orthologous gene expression in chickens, platypuses, and opossums, we found a stable expression ratio of X-linked genes in humans to their autosomal orthologs in other species (X:XX ≈ 1) across tissues and developmental stages, demonstrating stable dosage compensation in mammals. We also found that different epigenetic regulations contributed to the high tissue specificity and stage specificity of X-linked gene expression, thus affecting X:AA ratios. It could be concluded that the dynamics of X:AA ratios were attributed to the different gene contents and expression preferences of the X chromosome, rather than the stable dosage compensation.

Transcriptomic analysis of starch accumulation patterns in different glutinous sorghum seeds

Sorghum is a high-quality raw material for brewing white wine, and the starch content in seeds has a large impact on brewing quality. Transcriptomic data obtained from a glutinous variety (Liaonian3) and a non-glutinous variety (Liaoza10) at 3, 18, and 30 days after pollination were analyzed to identify genes associated with starch accumulation. The amylopectin content was significantly higher in Liaonian3 compared to Liaoza10, but the amylose content and total starch content were lower. There were 6634 differentially expressed genes found in Liaoza10 between 3 and 18 d after pollination, and 779 differentially expressed genes between 18 and 30 d after pollination. In Liaonian3, there were 6768 differentially expressed genes between 3 and 18 d after pollination, and 7630 differentially expressed genes between 18 and 30 d after pollination. Genes were grouped by expression profiles over the three time points and the profiles were analyzed for enrichment of gene ontology terms and biochemical pathways. Profile 1 (decreasing expression from 3 to 30 d) for Liaoza10 was enriched in ribosomes, metabolic pathways, and carbon metabolic pathways. Profile 0 (decreasing expression from 3 to 18 d and consistent expression from 18 to 30 d) was enriched in pathways related to sugar or starch metabolism. Although the starch accumulation rate in Liaonian3 and Liaoza10 showed a profile of increasing and then decreasing, the expression of genes related to starch synthesis gradually decreased with time since pollination, demonstrating the complexity of starch synthesis. According to orthologous gene alignment and expression analysis, 19 genes such as entrzID_8068390 and entrzID_8066807 were found to be the key genes for starch synthesis and glutinous and non-glutinous differentiation in sorghum grains.

Highly distinct genetic programs for peripheral nervous system formation in chordates

BackgroundVertebrates develop their peripheral nervous system (PNS) from transient unique embryonic structures, the neural crest, and the ectodermal placodes that are located at the border of the forming central nervous system. By contrast, in the invertebrate chordates, amphioxus and ascidians, a large part of the PNS originates at the opposite of the embryo, in the ventral ectoderm. In both groups, a biphasic mechanism regulates ventral PNS formation: high BMP levels specify a neurogenic territory within which glutamatergic epidermal sensory neuron formation is controlled by the Notch pathway. Given these similarities and the phylogenetic relationships within chordates, it is likely that ventral PNS is an ancestral feature in chordates and that it has been lost in vertebrates.ResultsIn order to get insights into the molecular control of ventral PNS formation and to test the hypothesis of their homology and potential contribution to the emergence of vertebrate PNS, we undertook a close comparison of ventral PNS formation in the ascidian Phallusia mammillata and the amphioxus Branchiostoma lanceolatum. Using timed RNA-seq series, we identified novel markers of the ventral PNS during different phases of its development in both species. By extensively determining the expression of paralogous and orthologous genes, we observed that only a minority of genes have a shared expression in the ventral PNS. However, a large fraction of ventral PNS orthologous genes are expressed in the dorsally forming PNS of vertebrates.ConclusionsOur work has significantly increased the molecular characterization of ventral PNS formation in invertebrate chordates. The low observed conservation of gene expression in the ventral PNS suggests that the amphioxus and ascidian ventral PNS are either not homologous, or alternatively extensive drift has occurred in their regulatory mechanisms following a long period (600 My) of separate evolution and accelerated evolution in the ascidian lineage. The homology to genes expressed in the dorsally forming PNS of vertebrates suggests that ancestral sensory neurons gene networks have been redeployed in vertebrates.

Pseudogenization of the rhizobium-responsive EXOPOLYSACCHARIDE RECEPTOR in Parasponia is a rare event in nodulating plants

BackgroundNodule symbiosis with diazotrophic Frankia or rhizobium occurs in plant species belonging to ten taxonomic lineages within the related orders Fabales, Fagales, Cucurbitales, and Rosales. Phylogenomic studies indicate that this nitrogen-fixing nodulation trait has a single evolutionary origin. In legume model plants, the molecular interaction between plant and rhizobium microsymbiont is mapped to a significant degree. A specific LysM-type receptor kinase, LjEPR3 in Lotus japonicus and MtLYK10 in Medicago truncatula, was found to act in a secondary identity-based mechanism, controlling intracellular rhizobium infection. Furthermore, LjEPR3 showed to bind surface exopolysaccharides of Mesorhizobium loti, the diazotrophic microsymbiont of L. japonicus. EPR3 orthologous genes are not unique to legumes. Surprisingly, however, its ortholog EXOPOLYSACCHARIDE RECEPTOR (EPR) is pseudogenized in Parasponia, the only lineage of non-legume plants that nodulate also with rhizobium.ResultsAnalysis of genome sequences showed that EPR3 orthologous genes are highly conserved in nodulating plants. We identified a conserved retrotransposon insertion in the EPR promoter region in three Parasponia species, which associates with defected transcriptional regulation of this gene. Subsequently, we studied the EPR gene of two Trema species as they represent the sister genus of Parasponia for which it is assumed it lost the nitrogen-fixing nodulation trait. Both Trema species possess apparently functional EPR genes that have a nodulation-specific expression profile when introduced into a Parasponia background. This indicates the EPR gene functioned in nodulation in the Parasponia-Trema ancestor.ConclusionWe conclude that nodule-specific expression of EPR3 orthologous genes is shared between the legume and Parasponia-Trema lineage, suggesting an ancestral function in the nitrogen-fixing nodulation trait. Pseudogenization of EPR in Parasponia is an exceptional case in nodulating plants. We speculate that this may have been instrumental to the microsymbiont switch -from Frankia to rhizobium- that has occurred in the Parasponia lineage and the evolution of a novel crack entry infection mechanism.

A transcriptomic atlas of Aedes aegypti reveals detailed functional organization of major body parts and gut regional specializations in sugar-fed and blood-fed adult females.

Mosquitoes transmit numerous pathogens, but large gaps remain in our understanding of their physiology. To facilitate explorations of mosquito biology, we have created Aegypti-Atlas (http://aegyptiatlas.buchonlab.com/), an online resource hosting RNAseq profiles of Ae. aegypti body parts (head, thorax, abdomen, gut, Malpighian tubules, ovaries), gut regions (crop, proventriculus, anterior and posterior midgut, hindgut), and a gut time course of blood meal digestion. Using Aegypti-Atlas, we provide insights into regionalization of gut function, blood feeding response, and immune defenses. We find that the anterior and posterior midgut possess digestive specializations which are preserved in the blood-fed state. Blood feeding initiates the sequential induction and repression/depletion of multiple cohorts of peptidases. With respect to defense, immune signaling components, but not recognition or effector molecules, show enrichment in ovaries. Basal expression of antimicrobial peptides is dominated by holotricin and gambicin, which are expressed in carcass and digestive tissues, respectively, in a mutually exclusive manner. In the midgut, gambicin and other effectors are almost exclusively expressed in the anterior regions, while the posterior midgut exhibits hallmarks of immune tolerance. Finally, in a cross-species comparison between Ae. aegypti and Anopheles gambiae midguts, we observe that regional digestive and immune specializations are conserved, indicating that our dataset may be broadly relevant to multiple mosquito species. We demonstrate that the expression of orthologous genes is highly correlated, with the exception of a 'species signature' comprising a few highly/disparately expressed genes. With this work, we show the potential of Aegypti-Atlas to unlock a more complete understanding of mosquito biology.

Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption

Human skin functions as a physical barrier, preventing the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to the skin landscape is the sebaceous gland. Mice devoid of sebocytes are prone to skin infection, yet our understanding of how sebocytes function in host defense is incomplete. Here, we show that the small proline-rich proteins, SPRR1 and SPRR2 are bactericidal in skin. SPRR1B and SPPR2A were induced in human sebocytes by exposure to the bacterial cell wall component lipopolysaccharide (LPS). Colonization of germ-free mice was insufficient to trigger increased SPRR expression in mouse skin, but LPS injected into mouse skin stimulated increased expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through activation of MYD88. Both mouse and human SPRR proteins displayed potent bactericidal activity against MRSA (methicillin-resistant Staphylococcus aureus), Pseudomonas aeruginosa, and skin commensals. Thus, Sprr1a-/-;Sprr2a-/- mice are more susceptible to MRSA and P. aeruginosa skin infection. Lastly, mechanistic studies demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. Taken together, these findings provide insight into the regulation and antimicrobial function of SPRR proteins in skin and how the skin defends the host against systemic infection.

Direct in vivo observation of the effect of codon usage bias on gene expression in Arabidopsis hybrids

Hybrids are the perfect materials to study cis regulatory elements because the two parental alleles are subjected to identical trans environments. There has been a debate on whether synonymous codon usage could affect gene expression. In vitro experiments found that luciferase genes with enhanced codon optimality showed elevated mRNA expression. However, the underlying mechanism is still unclear, and no direct evidence is observed to support this notion.By mapping the RNA-seq data of hybrids of Arabidopsis thaliana and Arabidopsis lyrata, we quantified the allele-specific reads and estimated the relative expression of orthologous genes. We focused on orthologous genes with dN = 0 and dS > 0, which means that they only differ in synonymous codon usage. We found that orthologous genes with higher codon optimality in A. thaliana tend to have higher expression levels of the A. thaliana allele.Codon usage bias could influence gene expression. This phenomenon is not only found in in vitro experiments but also supported by in vivo observations. Therefore, synonymous mutations could have a broad impact from multiple aspects and should not be automatically ignored in genomic studies. Key MessageIn Arabidopsis hybrids, alleles with higher codon optimality tend to have higher expression levels.

Transcriptional Profiling of Porcine HCC Xenografts Provides Insights Into Tumor Cell Microenvironment Signaling.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, representing the most common form of liver cancer. As HCC incidence and mortality continue to increase, there is a growing need for improved translational animal models to bridge the gap between basic HCC research and clinical practice to improve early detection and treatment strategies for this deadly disease. Recently the Oncopig cancer model—a novel transgenic swine model that recapitulates human cancer through Cre recombinase induced expression of KRASG12D and TP53R167H driver mutations—has been validated as a large animal translational model for human HCC. Due to the similar size, anatomy, physiology, immunology, genetics, and epigenetics between pigs and humans, the Oncopig has the potential to improve translation of novel diagnostic and therapeutic modalities into clinical practice. Recent studies have demonstrated the importance of tumor cells in shaping its surrounding microenvironment into one that is more proliferative, invasive, and metastatic; however, little is known about the impact of microenvironment signaling on HCC tumor biology and differential gene expression between HCC tumors and its tumor microenvironment (TME). In this study, transcriptional profiling was performed on Oncopig HCC xenograft tumors (n = 3) produced via subcutaneous injection of Oncopig HCC cells into severe combined immunodeficiency (SCID) mice. To differentiate between gene expression in the tumor and surrounding tumor microenvironment, RNA-seq reads originating from porcine (HCC tumor) and murine (microenvironment) cells were bioinformatically separated using Xenome. Principle component analysis (PCA) demonstrated clustering by group based on the expression of orthologous genes. Genes contributing to each principal component were extracted and subjected to functional analysis to identify alterations in pathway signaling between HCC cells and the microenvironment. Altered expression of genes associated with hepatic fibrosis deposition, immune response, and neo angiogenesis were observed. The results of this study provide insights into the interplay between HCC and microenvironment signaling in vivo, improving our understanding of the interplay between HCC tumor cells, the surrounding tumor microenvironment, and the impact on HCC development and progression.

Lineage-specific selection and the evolution of virulence in the Candida clade

Candida albicans is the most common cause of systemic fungal infections in humans and is considerably more virulent than its closest known relative, Candida dubliniensis. To investigate this difference, we constructed interspecies hybrids and quantified mRNA levels produced from each genome in the hybrid. This approach systematically identified expression differences in orthologous genes arising from cis-regulatory sequence changes that accumulated since the two species last shared a common ancestor, some 10 million y ago. We documented many orthologous gene-expression differences between the two species, and we pursued one striking observation: All 15 genes coding for the enzymes of glycolysis showed higher expression from the C. albicans genome than the C. dubliniensis genome in the interspecies hybrid. This pattern requires evolutionary changes to have occurred at each gene; the fact that they all act in the same direction strongly indicates lineage-specific natural selection as the underlying cause. To test whether these expression differences contribute to virulence, we created a C. dubliniensis strain in which all 15 glycolysis genes were produced at modestly elevated levels and found that this strain had significantly increased virulence in the standard mouse model of systemic infection. These results indicate that small expression differences across a deeply conserved set of metabolism enzymes can play a significant role in the evolution of virulence in fungal pathogens.

A Bioinformatics Model of Human Diseases on the Basis of Differentially Expressed Genes (of Domestic Versus Wild Animals) That Are Orthologs of Human Genes Associated with Reproductive-Potential Changes.

Earlier, after our bioinformatic analysis of single-nucleotide polymorphisms of TATA-binding protein-binding sites within gene promoters on the human Y chromosome, we suggested that human reproductive potential diminishes during self-domestication. Here, we implemented bioinformatics models of human diseases using animal in vivo genome-wide RNA-Seq data to compare the effect of co-directed changes in the expression of orthologous genes on human reproductive potential and during the divergence of domestic and wild animals from their nearest common ancestor (NCA). For example, serotonin receptor 3A (HTR3A) deficiency contributes to sudden death in pregnancy, consistently with Htr3a underexpression in guinea pigs (Cavia porcellus) during their divergence from their NCA with cavy (C. aperea). Overall, 25 and three differentially expressed genes (hereinafter, DEGs) in domestic animals versus 11 and 17 DEGs in wild animals show the direction consistent with human orthologous gene-markers of reduced and increased reproductive potential. This indicates a reliable association between DEGs in domestic animals and human orthologous genes reducing reproductive potential (Pearson’s χ2 test p < 0.001, Fisher’s exact test p < 0.05, binomial distribution p < 0.0001), whereas DEGs in wild animals uniformly match human orthologous genes decreasing and increasing human reproductive potential (p > 0.1; binomial distribution), thus enforcing the norm (wild type).

Insights into the diversification of subclade IVa bHLH transcription factors in Fabaceae

BackgroundFabaceae plants appear to contain larger numbers of subclade IVa basic-helix-loop-helix (bHLH) transcription factors than other plant families, and some members of this subclade have been identified as saponin biosynthesis regulators. We aimed to systematically elucidate the diversification of this subclade and obtain insights into the evolutionary history of saponin biosynthesis regulation in Fabaceae.ResultsIn this study, we collected sequences of subclade IVa bHLH proteins from 40 species, including fabids and other plants, and found greater numbers of subclade IVa bHLHs in Fabaceae. We confirmed conservation of the bHLH domain, C-terminal ACT-like domain, and exon-intron organisation among almost all subclade IVa members in model legumes, supporting the results of our classification. Phylogenetic tree-based classification of subclade IVa revealed the presence of three different groups. Interestingly, most Fabaceae subclade IVa bHLHs fell into group 1, which contained all legume saponin biosynthesis regulators identified to date. These observations support the co-occurrence and Fabaceae-specific diversification of saponin biosynthesis regulators. Comparing the expression of orthologous genes in Glycine max, Medicago truncatula, and Lotus japonicus, orthologues of MtTSAR1 (the first identified soyasaponin biosynthesis regulatory transcription factor) were not expressed in the same tissues, suggesting that group 1 members have gained different expression patterns and contributions to saponin biosynthesis during their duplication and divergence. On the other hand, groups 2 and 3 possessed fewer members, and their phylogenetic relationships and expression patterns were highly conserved, indicating that their activities may be conserved across Fabaceae.ConclusionsThis study suggests subdivision and diversification of subclade IVa bHLHs in Fabaceae plants. The results will be useful for candidate selection of unidentified saponin biosynthesis regulators. Furthermore, the functions of groups 2 and 3 members are interesting targets for clarifying the evolution of subclade IVa bHLH transcription factors in Fabaceae.

Retraction: The Arctic charr (Salvelinus alpinus) genome and transcriptome assembly

Arctic charr have a circumpolar distribution, persevere under extreme environmental conditions, and reach ages unknown to most other salmonids. The Salvelinus genus is primarily composed of species with genomes that are structured more like the ancestral salmonid genome than most Oncorhynchus and Salmo species of sister genera. It is thought that this aspect of the genome may be important for local adaptation (due to increased recombination) and anadromy (the migration of fish from saltwater to freshwater). In this study, we describe the generation of a new genetic map, the sequencing and assembly of the Arctic charr genome (GenBank accession: GCF_002910315.2) using the newly created genetic map and a previous genetic map, and present several analyses of the Arctic charr genes and genome assembly. The newly generated genetic map consists of 8,574 unique genetic markers and is similar to previous genetic maps with the exception of three major structural differences. The N50, identified BUSCOs, repetitive DNA content, and total size of the Arctic charr assembled genome are all comparable to other assembled salmonid genomes. An analysis to identify orthologous genes revealed that a large number of orthologs could be identified between salmonids and many appear to have highly conserved gene expression profiles between species. Comparing orthologous gene expression profiles may give us a better insight into which genes are more likely to influence species specific phenotypes.

Bacterial 3'UTRs: A Useful Resource in Post-transcriptional Regulation.

Bacterial messenger RNAs (mRNAs) are composed of 5′ and 3′ untranslated regions (UTRs) that flank the coding sequences (CDSs). In eukaryotes, 3′UTRs play key roles in post-transcriptional regulatory mechanisms. Shortening or deregulation of these regions is associated with diseases such as cancer and metabolic disorders. Comparatively, little is known about the functions of 3′UTRs in bacteria. Over the past few years, 3′UTRs have emerged as important players in the regulation of relevant bacterial processes such as virulence, iron metabolism, and biofilm formation. This MiniReview is an update for the different 3′UTR-mediated mechanisms that regulate gene expression in bacteria. Some of these include 3′UTRs that interact with the 5′UTR of the same transcript to modulate translation, 3′UTRs that are targeted by specific ribonucleases, RNA-binding proteins and small RNAs (sRNAs), and 3′UTRs that act as reservoirs of trans-acting sRNAs, among others. In addition, recent findings regarding a differential evolution of bacterial 3′UTRs and its impact in the species-specific expression of orthologous genes are also discussed.

The land plant-specific MIXTA-MYB lineage is implicated in the early evolution of the plant cuticle and the colonization of land.

The evolution of a lipid-based cuticle on aerial plant surfaces that protects against dehydration is considered a fundamental innovation in the colonization of the land by the green plants. However, key evolutionary steps in the early regulation of cuticle synthesis are still poorly understood, owing to limited studies in early-diverging land plant lineages. Here, we characterize a land plant specific subgroup 9 R2R3 MYB transcription factor MpSBG9, in the early-diverging land plant model Marchantia polymorpha, that is homologous to MIXTA proteins in vascular plants. The MpSBG9 functions as a key regulator of cuticle biosynthesis by preferentially regulating expression of orthologous genes for cutin formation, but not wax biosynthesis genes. The MpSBG9 also promotes the formation of papillate cells on the adaxial surface of M.polymorpha, which is consisitent with its canonical role in vascular plants. Our observations imply conserved MYB transcriptional regulation in the control of the cutin biosynthesis pathway as a core genetic network in the common ancestor of all land plants, implicating the land plant-specific MIXTA MYB lineage in the early origin and evolution of the cuticle.

Combinatorial Transcriptional Profiling of Mouse and Human Enteric Neurons Identifies Shared and Disparate Subtypes In Situ

The enteric nervous system (ENS) coordinates essential intestinal functions through the concerted action of diverse enteric neurons (ENs). However, integrated molecular knowledge of EN subtypes is lacking. To compare human and mouse ENs, we transcriptionally profiled healthy ENS from adult humans and mice. We aimed to identify transcripts marking discrete neuron subtypes and visualize conserved EN subtypes for humans and mice in multiple bowel regions. Human myenteric ganglia and adjacent smooth muscle were isolated by laser-capture microdissection for RNA sequencing. Ganglia-specific transcriptional profiles were identified by computationally subtracting muscle gene signatures. Nuclei from mouse myenteric neurons were isolated and subjected to single-nucleus RNA sequencing, totaling more than 4 billion reads and 25,208 neurons. Neuronal subtypes were defined using mouse single-nucleus RNA sequencing data. Comparative informatics between human andmouse data sets identified shared EN subtype markers, which were visualized in situ using hybridization chain reaction. Several EN subtypes in the duodenum, ileum, and colon are conserved between humans and mice based on orthologous gene expression. However, some EN subtype-specific genes from mice are expressed in completely distinct morphologically defined subtypes in humans. In mice, we identified several neuronal subtypes that stably express gene modules across all intestinal segments, with graded, regional expression of 1 or more marker genes. Our combined transcriptional profiling of human myenteric ganglia and mouse EN provides a rich foundation for developing novel intestinal therapeutics. There is congruency among some EN subtypes, but we note multiple species differences that should be carefully considered when relating findings from mouse ENS research to human gastrointestinal studies.

Systemic evolutionary changes in mammalian gene expression

Changes in gene expression play an important role in evolution and can be relevant to evolutionary medicine. In this work, a strong relationship was found between the statistical significance of evolutionary changes in the expression of orthologous genes in the five or six homologous mammalian tissues and the across-tissues unidirectionality of changes (i.e., they occur in the same direction in different tissues -- all upward or all downward). In the area of highly significant changes, the fraction of unidirectionally changed genes (UCG) was above 0.9 (random expectation is 0.03). This observation indicates that the most pronounced evolutionary changes in mammalian gene expression are systemic (i.e., they operate at the whole-organism level). The UCG are strongly enriched in the housekeeping genes. More specifically, in the human-chimpanzee comparison, the UCG are enriched in the pathways belonging to gene expression (translation is prominent), cell cycle control, ubiquitin-dependent protein degradation (mostly related to cell cycle control), apoptosis, and Parkinson's disease. In the human-macaque comparison, the two other neurodegenerative diseases (Alzheimer's and Huntington's) are added to the enriched pathways. The consolidation of gene expression changes at the level of pathways indicates that they are not neutral but functional. The systemic expression changes probably maintain the across-tissues balance of basic physiological processes in the course of evolution (e.g., during the movement along the fast-slow life axis). These results can be useful for understanding the variation in longevity and susceptibility to cancer and widespread neurodegenerative diseases. This approach can also guide the choice of prospective genes for studies aiming to decipher cis-regulatory code (the gene list is provided).