Comparative Genomics Approach Research Articles

Extraordinary diversity of the CD28/CTLA4 family across jawed vertebrates

Members of the CD28 family are critical for the control of immune cell activation. While CD28 and CTLA4 were previously identified in teleost fish, most members of the CD28 family have been described only in tetrapods. Using a comparative genomics approach, we found (co)orthologs of all members of the CD28 family both in Chondrichthyes and basal Osteichthyes groups, but not in Agnathans. Four additional members of the family were identified, which were present in both Chondrichthyes and Osteichthyes, some even in the tetrapod lineage but all of them absent in human. Herein, we extend the composition of the jawed vertebrate CD28 family to nine members: CD28, CTLA4, ICOS, CD28H, CD28HL1, CD28HL2, CD28HL3, CD28X and PD-1. Each of these genes had a single extracellular IgSF V domain, and conserved motifs in the V and the cytoplasmic domain. While a genomic cluster of three consecutive genes like CD28/CTLA4/ICOS was conserved across jawed vertebrates except in teleosts, the other members of the CD28 family were located on multiple chromosomes. Our findings show that these co-stimulatory/co-inhibitory receptors likely arose in early jawed vertebrates, and diversified when the Ig/TCR/MHC-based adaptive immunity emerged, heralding the advent of complex regulatory networks controlling lymphocyte activation.

From cactus to crop: genomic insights of a beneficial and non-pathogenic Curtobacterium flaccumfaciens strain and the evolution of its pathosystem.

With the advent of advanced sequencing technologies, new insights into the genomes of pathogens, including those in the genus Curtobacterium, have emerged. This research investigates a newly isolated C. flaccumfaciens strain 208 (Cf208) from Arthrocereus glaziovii, and endemic plant from Iron Quadrangle. Previous results show that Cf208 exhibits the potential to remediate soils, facilitating the growth of tomato plants. Furthermore, Cf208 showed no virulence towards bean plants, thus, confounding its phytopathogenic origins. Using a comprehensive comparative genomics approach, we analyzed the Cf208 genome against 34 other Curtobacterium strains, aiming to discern the genomic landmarks associated with its adaptation as an endophyte and its avirulence in bean crops. This revealed a predominant core genome comprising about 2426 genes (68%). Notably, Cf208 possesses a unique plasmid, pCF208-73, which contains 84 unique genes (2.5%). However, unlike the plasmids previously described for pathogenic strains, pCF208-73 does not feature genes associated with virulence induction. In contrast, while several genes traditionally linked to virulence, like pectate lyases and proteases were identified, but the T4P apparatus emerged as new crucial factor for understanding virulence in the Curtobacterium genus. The presence or absence of this apparatus, especially in strains from different clades, may determine their virulence towards leguminous plants. In conclusion, this work highlights the significance of comparative genomics in unraveling the complexities of pathogenicity within the Curtobacterium genus. Our findings suggest that, although the limited genetic variations, specific genes, particularly those linked to the T4P apparatus, play a fundamental role in their interactions with host plants.

Comparative Genomics Reveal Distinct Environment Preference and Functional Adaptation Among Lineages of Gemmatimonadota

Bacteria in the phylum Gemmatimonadota are globally distributed and abundant in microbial communities of various environments, playing an important role in driving biogeochemical cycling on Earth. Although high diversities in taxonomic composition and metabolic capabilities have been reported, little is known about the environmental preferences and associated functional features that facilitate adaptation among different Gemmatimonadota lineages. This study systematically analyzed the relationships between the environments, taxonomy, and functions of Gemmatimonadota lineages, by using a comparative genomics approach based on 1356 Gemmatimonadota genomes (213 high-quality and non-redundant genomes) available in a public database (NCBI). The taxonomic analysis showed that the 99.5% of the genomes belong to the class Gemmatimonadetes, and the rest of the genomes belong to the class Glassbacteria. Functional profiling revealed clear environmental preference among different lineages of Gemmatimonadota, and a marine group and two non-marine groups were identified and tested to be significantly different in functional composition. Further annotation and statistical comparison revealed a large number of functional genes (e.g., amiE, coxS, yfbK) that were significantly enriched in genomes from the marine group, supporting enhanced capabilities in energy acquisition, genetic information regulation (e.g., DNA repair), electrolyte homeostasis, and growth rate control. These genomic features are important for their survival in the marine environment, which is oligotrophic, variable, and with high salinity. The findings enhanced our understanding of the metabolic processes and environmental adaptation of Gemmatimonadota, and further advanced the understanding of the interactions of microorganisms and their habitats.

Breaking resistance: in silico subtractive and comparative genomics approaches for drug targeting in Bacteroides fragilis.

The purpose of this study was to identify potential novel drug targets for Bacteroides fragilis infections using bioinformatics techniques, such as subtractive and comparative genomics. Bacteroides fragilis is a frequently isolated anaerobic pathogen, particularly in the human digestive tract, where its pathogenesis and persistence are influenced by various virulence factors. By understanding these factors, the study aims to explore alternative therapeutic strategies and provide insights for the development of treatments against B. fragilis infections, particularly as alternatives to antibiotic therapy. A comparative subtractive genomic analysis was performed against the B. fragilis (strain CL07T12C05) to identify unique drug targets. The analysis includes the identification of non-paralogous, non-homologous, essential, and drug target like proteins. Moreover, a comprehensive structural analysis of the protein was conducted utilizing structure modeling and validation techniques, along with network topology analysis. Furthermore, a library comprising approximately 9000 FDA-approved compounds accessible in the DrugBank database was employed to conduct virtual screenings for compounds effective against the designated drug target. The top shortlisted compounds were further studied by employing MD simulations using GROMACS. This approach was chosen due to the established safety, efficacy, pharmacokinetics, and toxicity profiles of these compounds. As a result, B. fragilis (strain CL07T12C05) was found to possess 4595 proteins. Among these, 3518 were identified as non-homologous, 1508 deemed essential for bacterial viability, 348 exhibited drug-like properties, 203 were implicated in virulence, and 135 displayed antibiotic resistance. Following an extensive literature review, the protein Sialic acid O-acetyltransferase was chosen through a hierarchical shortlisting process as a potential therapeutic target. The ongoing research facilitated the repurposing of drug compounds: DB12411, DB02112, DB03591, and DB00192, as cost-effective medications against B. fragilis related infections. MD simulations analysis showed that DB12411 may be a potential drug candidate against Sialic acid O-acetyltransferase from B. fragilis. Through subtractive and comparative genomic analysis, Sialic acid O-acetyltransferase was identified as a promising drug target against Bacteroides fragilis. The findings indicate that compounds targeting this protein could potentially be effective in treating B. fragilis infections. However, further experimental validation is required to conclusively confirm their efficacy.

RERconverge Expansion: Using Relative Evolutionary Rates to Study Complex Categorical Trait Evolution.

Comparative genomics approaches seek to associate molecular evolution with the evolution of phenotypes across a phylogeny. Many of these methods lack the ability to analyze non-ordinal categorical traits with more than two categories. To address this limitation, we introduce an expansion to RERconverge that associates shifts in evolutionary rates with the convergent evolution of categorical traits. The categorical RERconverge expansion includes methods for performing categorical ancestral state reconstruction, statistical tests for associating relative evolutionary rates with categorical variables, and a new method for performing phylogeny-aware permutations, "permulations", on categorical traits. We demonstrate our new method on a three-category diet phenotype and we compare its performance to binary RERconverge analyses and two existing methods for comparative genomic analyses of categorical traits: phylogenetic simulations and a phylogenetic signal based method. We present an analysis of how the categorical permulations scale with the number of species and the number of categories included in the analysis. Our results show that our new categorical method outperforms phylogenetic simulations at identifying genes and enriched pathways significantly associated with the diet phenotypes and that the categorical ancestral state reconstruction drives an improvement in our ability to capture diet-related enriched pathways compared to binary RERconverge when implemented without user input on phenotype evolution. The categorical expansion to RERconverge will provide a strong foundation for applying the comparative method to categorical traits on larger data sets with more species and more complex trait evolution than have previously been analyzed.

Signature of viral fossils: a comparative genomics approach to understand the diversity of endogenous retroviruses in bats

Endogenous retroviruses (ERVs) are traces of past viral infections commonly found in vertebrate genomes. Many ERVs are tightly regulated by the host genomes and co-opted for various functions within the hosts. Bats are the only true volant mammals, with the smallest mammalian genomes and a high fraction of ERVs within the genomes. They are important hosts for various zoonotic viral pathogens and can effectively modulate their immune response to tolerate viral infections. Integrations of retroviruses have been implicated as one of the mechanisms by which bats have co-evolved strategies to combat viral infections. In this study, we investigated the diversity of ERVs in over 40 publicly available bat genomes to understand the distribution and the evolution of ERVs within bats. We observed all classes of ERVs within bat genomes including even the complex lenti retroviruses. Alpha and spuma retroviruses which are, generally considered rare in mammals, were common within bats. We observed a positive correlation between bat genome size and length of ERV elements. Interestingly, nearly 30% of the ERVs within bats are intact suggesting a recent origin or co-option by the host genome. Future studies focusing on comparative genomic and experimental data will be critical to understand the role of these ERVs in host genome evolution.

Exploring Synaptic Pathways in Traumatic Brain Injury: A Cross-Phenotype Genomics Approach.

Traumatic brain injury (TBI), a global leading cause of mortality and disability, lacks effective treatments to enhance recovery. Synaptic remodeling has been postulated as one mechanism that influences outcomes after TBI. We sought to investigate whether common mechanisms affecting synapse maintenance are shared between TBI and other neuropsychiatric conditions using pathway enrichment tools and genome-wide genotype data, with the goal of highlighting novel treatment targets. We leveraged an integrative approach, combining data from genome-wide association studies with pathway and gene-set enrichment analyses. Literature review-based and Reactome database-driven approaches were combined to identify synapse-related pathways of interest in TBI outcome and to assess for shared associations with conditions in which synapse-related pathobiological mechanisms have been implicated, including Alzheimer's disease, schizophrenia (SCZ), major depressive disorder, post-traumatic stress disorder, attention-deficit hyperactivity disorder, and autism spectrum disorder. Gene and pathway-level enrichment analyses were conducted using MAGMA and its extensions, e- and H-MAGMA, followed by Mendelian randomization to investigate potential causal associations. Of the 98 pathways tested, 32 were significantly enriched in the included conditions. In TBI outcome, we identified significant enrichment in five pathways: "Serotonin clearance from the synaptic cleft" (p = 0.0001), "Presynaptic nicotinic acetylcholine receptors" (p = 0.0003), "Postsynaptic nicotinic acetylcholine receptors" (p = 0.0003), "Highly sodium permeable postsynaptic acetylcholine nicotinic receptors" (p = 0.0001), and "Acetylcholine binding and downstream events" pathways (p = 0.0003). These associations highlight potential involvement of the cholinergic and serotonergic systems in post-TBI recovery. Three of those pathways were shared between TBI and SCZ, suggesting possible pathophysiologic commonalities. In this study, we utilize comparative and integrative genomic approaches across brain conditions that share synaptic mechanisms to explore the pathophysiology of TBI outcomes. Our results implicate associations between TBI outcome and synaptic pathways as well as pathobiological overlap with other neuropsychiatric diseases.

Evolution of plant cell-type-specific cis-regulatory elements.

Cis-regulatory elements (CREs) are critical in regulating gene expression, and yet understanding of CRE evolution remains challenging. Here, we constructed a comprehensive single-cell atlas of chromatin accessibility in Oryza sativa, integrating data from 103,911 nuclei representing 126 discrete cell states across nine distinct organs. We used comparative genomics to compare cell-type resolved chromatin accessibility between O. sativa and 57,552 nuclei from four additional grass species (Zea mays, Sorghum bicolor, Panicum miliaceum, and Urochloa fusca). Accessible chromatin regions (ACRs) had different levels of conservation depending on the degree of cell-type specificity. We found a complex relationship between ACRs with conserved noncoding sequences, cell-type specificity, conservation, and tissue-specific switching. Additionally, we found that epidermal ACRs were less conserved compared to other cell types, potentially indicating that more rapid regulatory evolution has occurred in the L1-derived epidermal layer of these species. Finally, we identified and characterized a conserved subset of ACRs that overlapped the repressive histone modification H3K27me3, implicating them as potentially silencer-like CREs maintained by evolution. Collectively, this comparative genomics approach highlights the dynamics of plant cell-type-specific CRE evolution.

Exploring pangenomic diversity and CRISPR-Cas evasion potential in jumbo phages: a comparative genomics study.

Jumbo phages are large bacterial viruses known for more than 50 years. However, only in recent years, a significant number of complete genome sequences of jumbo phages have become available. In this study, we employed comparative genomic approaches to investigate the genomic diversity and genome protection capabilities of the 331 jumbo phages. Our findings revealed that jumbo phages exhibit high genetic diversity, with only a few genes being relatively conserved across jumbo phages. Interestingly, our data suggest that jumbo phages employ yet-to-be-identified strategies to protect their DNA from the host immune system, such as CRISPR-Cas.

Comparative genome-wide identification and characterization of SET domain-containing and JmjC domain-containing proteins in piroplasms

BackgroundSET domain-containing histone lysine methyltransferases (HKMTs) and JmjC domain-containing histone demethylases (JHDMs) are essential for maintaining dynamic changes in histone methylation across parasite development and infection. However, information on the HKMTs and JHDMs in human pathogenic piroplasms, such as Babesia duncani and Babesia microti, and in veterinary important pathogens, including Babesia bigemina, Babesia bovis, Theileria annulata and Theileria parva, is limited.ResultsA total of 38 putative KMTs and eight JHDMs were identified using a comparative genomics approach. Phylogenetic analysis revealed that the putative KMTs can be divided into eight subgroups, while the JHDMs belong to the JARID subfamily, except for BdJmjC1 (BdWA1_000016) and TpJmjC1 (Tp Muguga_02g00471) which cluster with JmjC domain only subfamily members. The motifs of SET and JmjC domains are highly conserved among piroplasm species. Interspecies collinearity analysis provided insight into the evolutionary duplication events of some SET domain and JmjC domain gene families. Moreover, relative gene expression analysis by RT‒qPCR demonstrated that the putative KMT and JHDM gene families were differentially expressed in different intraerythrocytic developmental stages of B. duncani, suggesting their role in Apicomplexa parasite development.ConclusionsOur study provides a theoretical foundation and guidance for understanding the basic characteristics of several important piroplasm KMT and JHDM families and their biological roles in parasite differentiation.

Advancing Source Tracking: Systematic Review and Source-Specific Genome Database Curation of Fecally Shed Prokaryotes.

Advancements within fecal source tracking (FST) studies are complicated by a lack of knowledge regarding the genetic content and distribution of fecally shed microbial populations. To address this gap, we performed a systematic literature review and curated a large collection of genomes (n = 26,018) representing fecally shed prokaryotic species across broad and narrow source categories commonly implicated in FST studies of recreational waters (i.e., cats, dogs, cows, seagulls, chickens, pigs, birds, ruminants, human feces, and wastewater). We find that across these sources the total number of prokaryotic genomes recovered from materials meeting our initial inclusion criteria varied substantially across fecal sources: from none in seagulls to 9,085 in pigs. We examined genome sequences recovered from these metagenomic and isolation-based studies extensively via comparative genomic approaches to characterize trends across source categories and produce a finalized genome database for each source category which is available online (n = 12,730). On average, 81% of the genomes representing species-level populations occur only within a single source. Using fecal slurries to test the performance of each source database, we report read capture rates that vary with fecal source alpha diversity and database size. We expect this resource to be useful to FST-related objectives, One Health research, and sanitation efforts globally.

De Novo Genome Assembly of Toniniopsis dissimilis (Ramalinaceae, Lecanoromycetes) from Long Reads Shows a Comparatively High Composition of Biosynthetic Genes Putatively Involved in Melanin Synthesis.

Lichens have developed numerous adaptations to optimize their survival in various environmental conditions, largely by producing secondary compounds by the fungal partner. They often have antibiotic properties and are involved in protection against intensive UV radiation, pathogens, and herbivores. To contribute to the knowledge of the arsenal of secondary compounds in a crustose lichen species, we sequenced and assembled the genome of Toniniopsis dissimilis, an indicator of old-growth forests, using Oxford Nanopore Technologies (ONT, Oxford, UK) long reads. Our analyses focused on biosynthetic gene clusters (BGCs) and specifically on Type I Polyketide (T1PKS) genes involved in the biosynthesis of polyketides. We used the comparative genomic approach to compare the genome of T. dissimilis with six other members of the family Ramalinaceae and twenty additional lichen genomes from the database. With only six T1PKS genes, a comparatively low number of biosynthetic genes are present in the T. dissimilis genome; from those, two-thirds are putatively involved in melanin biosynthesis. The comparative analyses showed at least three potential pathways of melanin biosynthesis in T. dissimilis, namely via the formation of 1,3,6,8-tetrahydroxynaphthalene, naphthopyrone, or YWA1 putative precursors, which highlights its importance in T. dissimilis. In addition, we report the occurrence of genes encoding ribosomally synthesized and posttranslationally modified peptides (RiPPs) in lichens, with their highest number in T. dissimilis compared to other Ramalinaceae genomes. So far, no function has been assigned to RiPP-like proteins in lichens, which leaves potential for future research on this topic.

Designing primer-probe sets for Escherichia coli and E. coli O157 detection: Comparative genomic approach and food interference assessment

This study aimed to develop novel primer-probe sets specifically optimized for detecting E. coli and E. coli O157 through comparative genomic analysis. Genomic data from 2396 E. coli strains, including 228 strains of E. coli O157, were retrieved from the National Center for Biotechnology Information (NCBI). From the analysis, yegR and GDP-mannose mannosyl hydrolase (GDPMH) genes were selected as primer targets for E. coli and E. coli O157:H7, respectively. The sensitivity and specificity of the designed primer-probe sets were evaluated in 48 E. coli strains (including 30 E. coli O157) and 17 non-E. coli strains, totaling 65 strains, and the results indicated high sensitivity and specificity. Tryptic soy broth (TSB), carrots, chicken, milk, potatoes, apple juice, and orange juice did not significantly interfere with detecting E. coli and E. coli O157; however, 50% potato samples did. The efficacy of the designed primers was compared among ground pork, lettuce, and potato samples. Reduced detection efficiency was noted in the lettuce and potato samples. Wavelength interference with components of the lettuce homogenate may have reduced detection efficiency. For potato samples, the high affinity of chlorogenic acid, a compound found in potatoes, for Taq DNA polymerase, a component of the mastermix, contributed to the reduced detection efficiency. The primer and probe sets described in this study, coupled with an understanding of possible interference from food components, will aid in detecting E. coli O157 in the food industry.

Comparative Genomics of Limosilactobacillus pontis Strains: Niche-Specific Variations and Adaptations

Limosilactobacillus pontis (L. pontis) is a species of lactic acid bacteria (LAB) found in various products, including fermented milk, sourdough, and broiler chickens’ gastrointestinal tracts. However, the evolutionary strategies and genomic features of the species remain unknown, which limits its application. In this study, whole-genome sequencing was carried out to investigate the genomic characteristics and evolutionary strategies of L. pontis, combined with a comparative genomic approach, providing the necessary theoretical basis for its application. The genomic sequences in this study included three published genomic sequences and two strains isolated from fermented milk in our lab in Inner Mongolia, China. The mean genome size of the five L. pontis strains was 1.70 Mb, and the mean DNA G + C content was 53.06%. L. pontis was a species with higher G + C content in LAB. The phylogenetic evolutionary tree for the core genes showed that the strains from the same sources were aggregated into a cluster. There were some differences in the genomic information and phylogenetic relationships amongst L. pontis from different sources. An analysis of the annotation results identified differences in the functional genes, carbohydrate-active enzymes, and bacteriocins amongst different isolated strains, which were related to the environment. L. pontis was rich in glycosyltransferases, especially in strains isolated from fermented milk, indicating that they had higher sugar synthesis abilities. It is worth mentioning that only the L. pontis strains isolated in our laboratory identified the bacteriocin operon, which may increase its application potential. The genomic characteristics and evolutionary process of L. pontis were analyzed by comparative genomics, and this study explored the differences in the functional genes amongst the strains, aiming to provide new insights into the genetic characteristics and niche adaptations of L. pontis.

A genome resource for the marine annelid Platynereis dumerilii.

The marine annelid Platynereis dumerilii is a model organism used in many research areas including evolution and development, neurobiology, ecology and regeneration. Here we present the genomes of P. dumerilii and of the closely related P. massiliensis and P. megalops, to facilitate comparative genomic approaches and help explore Platynereis biology. We used long-read sequencing technology and chromosomal-conformation capture along with extensive transcriptomic resources to obtain and annotate a draft genome assembly of ~1.47 Gbp for P. dumerilii, of which more than half represent repeat elements. We predict around 29,000 protein-coding genes, with relatively large intron sizes, over 38,000 non-coding genes, and 580 miRNA loci. We further explore the high genetic variation (~3% heterozygosity) within the Platynereis species complex. Gene ontology reveals the most variable loci to be associated with pigmentation, development and immunity. The current work sets the stage for further development of Platynereis genomic resources.

Genomic and epidemiological evidence for the emergence of a L. infantum/L. donovani hybrid with unusual epidemiology in northern Italy.

Leishmania (L.) infantum is one of the main causative agents of animal and human leishmaniasis across many endemic areas in South America, Europe, North Africa, and Asia. Despite its clinical significance, little is known about the genetic diversity of L. infantum circulating in a given endemic area. Here, we investigate this important open question by applying a comparative genomics approach to seven L. infantum isolates from different hosts and Italian regions, including the northern part of the country (Emilia-Romagna, RER), Sicily, and Sardinia, as an initial attempt to explore the breadth of parasite genetic heterogeneity in Italy. Additionally, microsatellite analysis was carried out to compare the isolates from RER with other 70 L. infantum strains from the same region as well as 65 strains belonging to the L. donovani complex from other countries. We revealed important karyotypic instability and identified strain-specific changes in gene dosage, which affected important virulence factors such as amastins and surface antigen-like proteins. Single nucleotide polymorphism-based clustering analysis of these genomes together with over 80 publicly available L. infantum and L. donovani genomes placed the Italian isolates into three geographically distinct clusters within the Mediterranean basin and uncovered three isolates clustering with putative L. infantum/L. donovani hybrids isolated in Cyprus. As judged by microsatellite profiling, these hybrid isolates are representative of a sub-population of parasites circulating in northern Italy that preferentially infect humans but not dogs. Our results place Italy at the crossroads of L. infantum infection in the Mediterranean and call attention to the public health risk represented by the introduction of non-European Leishmania species.IMPORTANCEThis study closes important knowledge gaps with respect to Leishmania (L.) infantum genetic heterogeneity in a given endemic country, as exemplified here for Italy, and reveals genetic hybridization as a main cause for re-emerging human leishmaniasis in northern Italy. The observed high diversity of Leishmania parasites on the Italian peninsula suggests different geographical origins, with genomic adaptation to various ecologies affecting both pathogenicity and transmission potential. This is documented by the discovery of a putative L. infantum/L. donovani hybrid strain, which has been shown to preferentially infect humans but not dogs. Our results provide important information to health authorities, which need to consider the public health risk represented by the introduction of new Leishmania species into EU countries due to population displacement or travel from countries where exotic/allochthonous parasite species are endemic.

Chromosome-level genome assemblies of 2 hemichordates provide new insights into deuterostome origin and chromosome evolution.

Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.

The identification of retro-DNAs in primate genomes as DNA transposons mobilizing via retrotransposition.

Mobile elements (MEs) constitute a major portion of the genome in primates and other higher eukaryotes, and they play important role in genome evolution and gene function. MEs can be divided into two fundamentally different classes: DNA transposons which transpose in the genome in a "cut-and-paste" style, and retrotransposons which propagate in a "copy-and-paste" fashion via a process involving transcription and reverse-transcription. In primate genomes, DNA transposons are mostly dead, while many retrotransposons are still highly active. We report here the identification of a unique group of MEs, which we call "retro-DNAs", for their combined characteristics of these two fundamentally different ME classes. A comparative computational genomic approach was used to analyze the reference genome sequences of 10 primate species consisting of five apes, four monkeys, and marmoset. From our analysis, we identified a total of 1,750 retro-DNAs, representing 748 unique insertion events in the genomes of ten primate species including human. These retro-DNAs contain sequences of DNA transposons but lack the terminal inverted repeats (TIRs), the hallmark of DNA transposons. Instead, they show characteristics of retrotransposons, such as polyA tails, longer target-site duplications (TSDs), and the "TT/AAAA" insertion site motif, suggesting the use of the L1-based target- primed reverse transcription (TPRT) mechanism. At least 40% of these retro-DNAs locate into genic regions, presenting potentials for impacting gene function. More interestingly, some retro-DNAs, as well as their parent sites, show certain levels of expression, suggesting that they have the potential to create more retro-DNA copies in the present primate genomes. Although small in number, the identification of these retro-DNAs reveals a new mean for propagating DNA transposons in primate genomes without active canonical DNA transposon activity. Our data also suggest that the TPRT machinery may transpose a wider variety of DNA sequences in the genomes.

Conservation of the Pal/Rim Pathway in Ustilaginomycetes.

The ability of fungi to effectively sense and internalize signals related to extracellular changing environments is essential for survival. This adaptability is particularly important for fungal pathogens of humans and plants that must sense and respond to drastic environmental changes when colonizing their hosts. One of the most important physicochemical factors affecting fungal growth and development is the pH. Ascomycota fungal species possess mechanisms such as the Pal/Rim pathway for external pH sensing and adaptation. However, the conservation of this mechanism in other fungi, such as Ustilaginomycetes is still little studied. To overcome this knowledge gap, we used a comparative genomic approach to explore the conservation of the Pal/Rim pathway in the 13 best sequenced and annotated Ustilaginomycetes. Our findings reveal that the Rim proteins and the Endosomal Sorting Complex Required for Transport (ESCRT) proteins are conserved in Ustilaginomycetes. They conserve the canonical domains present in Pal/Rim and ESCRT proteins of Ascomycota. This study sheds light on the molecular mechanisms used by these fungi for responding to extracellular stresses such as the pH, and open the door to further experimentations for understanding the molecular bases of the signaling in Ustilaginomycetes.

Emerging roles of long non-coding RNAs in human epilepsy.

Genome-scale biological studies conducted in the post-genomic era have revealed that two-thirds of human genes do not encode proteins. Most functional non-coding RNA transcripts in humans are products of long non-coding RNA (lncRNA) genes, an abundant but still poorly understood class of human genes. As a result of their fundamental and multitasking regulatory roles, lncRNAs are associated with a wide range of human diseases, including neurological disorders. Approximately 40% of lncRNAs are specifically expressed in the brain, and many of them exhibit distinct spatiotemporal patterns of expression. Comparative genomics approaches have determined that 65%-75% of human lncRNA genes are primate-specific and hence can be posited as a contributing potential cause of the higher-order complexity of primates, including human, brains relative to those of other mammals. Although lncRNAs present important mechanistic examples of epileptogenic functions, the human/primate specificity of lncRNAs questions their relevance in rodent models. Here, we present an in-depth review that supports the contention that human lncRNAs are direct contributors to the etiology and pathogenesis of human epilepsy, as a means to accelerate the integration of lncRNAs into clinical practice as potential diagnostic biomarkers and therapeutic targets. Meta-analytically, the major finding of our review is the commonality of lncRNAs in epilepsy and cancer pathogenesis through mitogen-activated protein kinase (MAPK)-related pathways. In addition, neuroinflammation may be a relevant part of the common pathophysiology of cancer and epilepsy. LncRNAs affect neuroinflammation-related signaling pathways such as nuclear factor kappa- light- chain- enhancer of activated B cells (NF-κB), Notch, and phosphatidylinositol 3- kinase/ protein kinase B (Akt) (PI3K/AKT), with the NF-κB pathway being the most common. Besides the controversy over lncRNA research in non-primate models, whether neuroinflammation is triggered by injury and/or central nervous system (CNS) toxicity during epilepsy modeling in animals or is a direct consequence of epilepsy pathophysiology needs to be considered meticulously in future studies.