Number Of Pseudogenes Research Articles

Many purported pseudogenes in bacterial genomes are bona fide genes

BackgroundMicrobial genomes are largely comprised of protein coding sequences, yet some genomes contain many pseudogenes caused by frameshifts or internal stop codons. These pseudogenes are believed to result from gene degradation during evolution but could also be technical artifacts of genome sequencing or assembly.ResultsUsing a combination of observational and experimental data, we show that many putative pseudogenes are attributable to errors that are incorporated into genomes during assembly. Within 126,564 publicly available genomes, we observed that nearly identical genomes often substantially differed in pseudogene counts. Causal inference implicated assembler, sequencing platform, and coverage as likely causative factors. Reassembly of genomes from raw reads confirmed that each variable affects the number of putative pseudogenes in an assembly. Furthermore, simulated sequencing reads corroborated our observations that the quality and quantity of raw data can significantly impact the number of pseudogenes in an assembler dependent fashion. The number of unexpected pseudogenes due to internal stops was highly correlated (R2 = 0.96) with average nucleotide identity to the ground truth genome, implying relative pseudogene counts can be used as a proxy for overall assembly correctness. Applying our method to assemblies in RefSeq resulted in rejection of 3.6% of assemblies due to significantly elevated pseudogene counts. Reassembly from real reads obtained from high coverage genomes showed considerable variability in spurious pseudogenes beyond that observed with simulated reads, reinforcing the finding that high coverage is necessary to mitigate assembly errors.ConclusionsCollectively, these results demonstrate that many pseudogenes in microbial genome assemblies are actually genes. Our results suggest that high read coverage is required for correct assembly and indicate an inflated number of pseudogenes due to internal stops is indicative of poor overall assembly quality.

Barcoding Fails to Delimit Species in Mongolian Oedipodinae (Orthoptera, Acrididae).

Mongolia, a country in central Asia, with its vast grassland areas represents a hotspot for Orthoptera diversity, especially for the Acrididae. For Mongolia, 128 Acrididae species have been documented so far, of which 41 belong to the subfamily Oedipodinae (band-winged grasshoppers). Yet, few studies concerning the distribution and diversity of Oedipodinae have been conducted in this country. Molecular genetic data is almost completely absent, despite its value for species identification and discovery. Even, the simplest and most used data, DNA barcodes, so far have not been generated for the local fauna. Therefore, we generated the first DNA barcode data for Mongolian band-winged grasshoppers and investigated the resolution of this marker for species delimitation. We were able to assemble 105 DNA barcode (COI) sequences of 35 Oedipodinae species from Mongolia and adjacent countries. Based on this data, we reconstructed maximum likelihood and Bayesian inference phylogenies. We, furthermore, conducted automatic barcode gap discovery and used the Poisson tree process (PTP) for species delimitation. Some resolution was achieved at the tribe and genus level, but all delimitation methods failed to differentiate species by using the COI region. This lack of resolution may have multiple possible reasons, which likely differ between taxa: the lack of resolution in the Bryodemini may be partially explained by their massive genomes, implying the potential presence of large numbers of pseudogenes, while within the Sphingonotini incomplete lineage sorting and incorrect taxonomy are more likely explanations for the lack of signal. Further studies based on a larger number of gene fragments, including nuclear DNA, are needed to distinguish the species also at the molecular level.

Tracking the footsteps of Burkholderia mallei: determination of the molecular differences and potential resistance genes.

Chemical biological radiological nuclear threats are at an important point in the agenda of world health today, as they can cause mass deaths. B. mallei attracts attention as a potential biological warfare agent due to its features such as multidrug resistance, a rapid transmission mechanism via aerosol, the absence of a complete treatment protocol for the infection it causes, and the absence of an approved vaccine for protection against the bacteria. B. mallei suspect samples must be studied by experienced personnel in biosafety level III laboratories. B mallei is a difficult and troublesome pathogen to diagnose and many unknowns about B. mallei today. Therefore, the aim of the study was to determine the molecular differences and potential resistance genes of B mallei strains. Determination of the molecular differences and potential resistance genes of B mallei strains with new bioinformatics approaches by comparatively examining the data of 29 B mallei strains, 10 of which were isolated from Türkiye, on the genome list of the National Biotechnology Information Center (NCBI). According to the genome annotations of the origins, the origin containing the highest number of CDS which is 5172 was found as the 11th strain obtained in Türkiye in 1949. The origin with the highest number of pseudogenes was determined as 23,344 (China 7) origin. Two hundred and eighty-five pseudogenes found in this strain were obtained from a knee effusion in Myanmar. According to chromosome 2 data, B. mallei strain was determined as the most similar strain to ATCC 23344, line 11 with NCTC 10229 strain, and SAVP1 strain was determined as the least similar strain. When the antimicrobial resistance gene markers of the isolates included in the study were examined, amrA and amrB, qacG ade, Burkholderia pseudomallei Omp38 were found to be carrying. In terms of public health, it was thought that the data obtained as a result of our study about B mallei, which is defined as a biological weapon, is very valuable for creating treatment protocols to be applied to possible epidemics in the future. In addition, the available genetic epidemiological data of these strains belonging to a category that is dangerous to work with in a laboratory environment were reviewed.

A large-scale phylogeny-guided analysis of pseudogenes in Pseudomonas aeruginosa bacterium.

Pseudogenes, once considered "junk DNA" based on the incorrect assumption that the absence of full coding potential means a complete lack of functionality, have recently become a subject of significant interest in the scientific community. Concurrently, it is widely assumed that bacterial genomes are compact and have a high density of coding genes with little room for non-coding genes, including pseudogenes. A key aspect of genome annotation is the correct identification of genes and the distinction between coding genes and pseudogenes, as it directly impacts functional and comparative genomics studies. In this study, we analyzed the genomic data of 4,699 strains of the bacterium Pseudomonas aeruginosa (P. aeruginosa) as they exhibit high variability in the number of annotated pseudogenes. In particular, we looked for correlations between the number of pseudogenes and other genomic and meta-features of the strains. We identified clusters of orthologous genes and pseudogenes and compared cluster size distributions and length homogeneity within clusters. We then mapped and examined orthology relationships between genes and pseudogenes. Additionally, we generated a phylogenetic tree of the strains and found that phylogenetically related strains are more homogeneous in the number of pseudogenes and share a significant amount of pseudogenes. Finally, we delved into clusters of orthologous genes and pseudogenes and quantified their phylogenetic neighborhood, classifying pseudogenes into evolutionary preserved pseudogenes, mis-annotated pseudogenes, or pseudogenes formed by failed horizontal transfer events. This in-depth study provides important insights that can be incorporated into pseudogene annotation pipelines in the future. IMPORTANCE Accurate annotation of genes and pseudogenes is vital for comparative genomics analysis. Recent studies have shown that bacterial pseudogenes have an important role in regulatory processes and can provide insight into the evolutionary history of homologous genes or the genome as a whole. Due to pseudogenes' nature as non-functional genes, there is no commonly accepted definition of a pseudogene, which poses difficulties in verifying the annotation through experimental methods and resolving discrepancies among different annotation techniques. Our study introduces an in-depth analysis of annotated genes and pseudogenes and insights that can be incorporated into improved pseudogene annotation pipelines in the future.

Genomic Characteristics of Emerging Intraerythrocytic Anaplasma capra and High Prevalence in Goats, China.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

Constructing Integrative ceRNA Networks and Finding Prognostic Biomarkers in Renal Cell Carcinoma.

Inspired by a newly discovered gene regulation mechanism known as competing endogenous RNA (ceRNA) interactions, several computational methods have been proposed to generate ceRNA networks. However, most of these methods have focused on deriving restricted types of ceRNA interactions such as lncRNA-miRNA-mRNA interactions. Competition for miRNA-binding occurs not only between lncRNAs and mRNAs but also between lncRNAs or between mRNAs. Furthermore, a large number of pseudogenes also act as ceRNAs, thereby regulate other genes. In this study, we developed a general method for constructing integrative networks of all possible interactions of ceRNAs in renal cell carcinoma (RCC). From the ceRNA networks we derived potential prognostic biomarkers, each of which is a triplet of two ceRNAs and miRNA (i.e., ceRNA-miRNA-ceRNA). Interestingly, some prognostic ceRNA triplets do not include mRNA at all, and consist of two non-coding RNAs and miRNA, which have been rarely known so far. Comparison of the prognostic ceRNA triplets to known prognostic genes in RCC showed that the triplets have a better predictive power of survival rates than the known prognostic genes. Our approach will help us construct integrative networks of ceRNAs of all types and find new potential prognostic biomarkers in cancer.

Woronichinia naegeliana: A common nontoxigenic component of temperate freshwater cyanobacterial blooms with 30% of its genome in transposons

Monitoring in the U.S. state of Washington across the period 2007–2019 showed that Woronichinia has been present in many lakes state-wide. This cyanobacterium was commonly dominant or sub-dominant in cyanobacterial blooms in the wet temperate region west of the Cascade Mountains. In these lakes, Woronichinia often co-existed with Microcystis, Dolichospermum and Aphanizomenon flos-aquae and the cyanotoxin microcystin has often been present in those blooms, although it has not been known whether Woronichinia is a toxin producer. We report the first complete genome of Woronichinia naegeliana WA131, assembled from the metagenome of a sample collected from Wiser Lake, Washington, in 2018. The genome contains no genes for cyanotoxin biosynthesis or taste-and-odor compounds, but there are biosynthetic gene clusters for other bioactive peptides, including anabaenopeptins, cyanopeptolins, microginins and ribosomally produced, post-translationally modified peptides. Genes for photosynthesis, nutrient acquisition, vitamin synthesis and buoyancy that are typical of bloom-forming cyanobacteria are present, although nitrate and nitrite reductase genes are conspicuously absent. However, the 7.9 Mbp genome is 3–4 Mbp larger than those of the above-mentioned frequently co-existing cyanobacteria. The increased genome size is largely due to an extraordinary number of insertion sequence elements (transposons), which account for 30.3% of the genome and many of which are present in multiple copies. The genome contains a relatively large number of pseudogenes, 97% of which are transposase genes. W. naegeliana WA131 thus seems to be able to limit the potentially deleterious effects of high rates of recombination and transposition to the mobilome fraction of its genome.

Supergroup F Wolbachia with extremely reduced genome: transition to obligate insect symbionts

BackgroundWolbachia belong to highly abundant bacteria which are frequently found in invertebrate microbiomes and manifest by a broad spectrum of lifestyles from parasitism to mutualism. Wolbachia supergroup F is a particularly interesting clade as it gave rise to symbionts of both arthropods and nematodes, and some of its members are obligate mutualists. Investigations on evolutionary transitions among the different symbiotic stages have been hampered by a lack of the known diversity and genomic data for the supergroup F members.ResultsBased on amplicon screening, short- and long-read WGS approaches, and laser confocal microscopy, we characterize five new supergroup F Wolbachia strains from four chewing lice species. These strains reached different evolutionary stages and represent two remarkably different types of symbiont genomes. Three of the genomes resemble other known members of Wolbachia F supergroup, while the other two show typical signs of ongoing gene inactivation and removal (genome size, coding density, low number of pseudogenes). Particularly, wMeur1, a symbiont fixed in microbiomes of Menacanthus eurysternus across four continents, possesses a highly reduced genome of 733,850 bp. The horizontally acquired capacity for pantothenate synthesis and localization in specialized bacteriocytes suggest its obligate nutritional role.ConclusionsThe genome of wMeur1 strain, from the M. eurysternus microbiome, represents the smallest currently known Wolbachia genome and the first example of Wolbachia which has completed genomic streamlining as known from the typical obligate symbionts. This points out that despite the large amount and great diversity of the known Wolbachia strains, evolutionary potential of these bacteria still remains underexplored. The diversity of the four chewing lice microbiomes indicates that this vast parasitic group may provide suitable models for further investigations.7WEvJWu-ue-vx6WDrtUrQBVideo

Phenotype testing, genome analysis, and metabolic interactions of three lactic acid bacteria strains existing as a consortium in a naturally fermented milk.

This work reports the characterization of three lactic acid bacteria (LAB) strains –Lactococcus lactis LA1, Lactococcus cremoris LA10, and Lactiplantibacillus plantarum LA30– existing as a stable consortium in a backslopping-inoculated, naturally fermented milk (NFM). This study aimed at uncovering the biochemical and genetic basis of the stability of the consortium and the cooperativity among the strains during milk fermentation. All three strains were subjected to phenotyping, covering the utilization of carbohydrates, enzyme activity, and antibiotic resistance. The strains were grown in milk individually, as well as in all possible combinations, and the resulting fermented product was analyzed for sugars, organic acids, and volatile compounds. Finally, the genomes of the three strains were sequenced and analyzed for genes associated with technological and safety properties. As expected, wide phenotypic diversity was seen between the strains. Lactococcus cremoris LA10 was the only strain to reach high cell densities and coagulate milk alone after incubation at 22°C for 24 h; congruently, it possessed a gene coding for a PrtP type II caseinolytic protease. Compared to any other fermentation, acetaldehyde concentrations were greater by a factor of six when all three strains grew together in milk, suggesting that its production might be the result of an interaction between them. Lactococcus lactis LA1, which carried a plasmid-encoded citQRP operon, was able to utilize milk citrate producing diacetyl and acetoin. No genes encoding virulence traits or pathogenicity factors were identified in any of the strains, and none produced biogenic amines from amino acid precursors, suggesting them to be safe. Lactiplantibacillus plantarum LA30 was susceptible to tetracycline, although it harbors a disrupted antibiotic resistance gene belonging to the tetM/tetW/tetO/tetS family. All three strains contained large numbers of pseudogenes, suggesting that they are well adapted (“domesticated”) to the milk environment. The consortium as a whole or its individual strains might have a use as a starter or as starter components for dairy fermentations. The study of simple consortia, such as that existing in this NFM, can help reveal how microorganisms interact with one another, and what influence they may have on the sensorial properties of fermented products.

Differences in pseudogene evolution contributed to the contrasting flavors of turnip and Chiifu, two Brassica rapa subspecies

Pseudogenes are important resources for investigation of genome evolution and genomic diversity because they are nonfunctional but have regulatory effects that influence plant adaptation and diversification. However, few systematic comparative analyses of pseudogenes in closely related species have been conducted. Here, we present a turnip (Brassica rapa ssp. rapa) genome sequence and characterize pseudogenes among diploid Brassica species/subspecies. The results revealed that the number of pseudogenes was greatest in Brassica oleracea (CC genome), followed by B. rapa (AA genome) and then Brassica nigra (BB genome), implying that pseudogene differences emerged after species differentiation. In Brassica AA genomes, pseudogenes were distributed asymmetrically on chromosomes because of numerous chromosomal insertions/rearrangements, which contributed to the diversity among subspecies. Pseudogene differences among subspecies were reflected in the flavor-related glucosinolate (GSL) pathway. Specifically, turnip had the highest content of pungent substances, probably because of expansion of the methylthioalkylmalate synthase-encoding gene family in turnips; these genes were converted into pseudogenes in B. rapa ssp. pekinensis (Chiifu). RNA interference-based silencing of the gene encoding 2-oxoglutarate-dependent dioxygenase 2, which is also associated with flavor and anticancer substances in the GSL pathway, resulted in increased abundance of anticancer compounds and decreased pungency of turnip and Chiifu. These findings revealed that pseudogene differences between turnip and Chiifu influenced the evolution of flavor-associated GSL metabolism-related genes, ultimately resulting in the different flavors of turnip and Chiifu.

The Genome of Rhyzopertha dominica (Fab.) (Coleoptera: Bostrichidae): Adaptation for Success.

The lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae), is a major global pest of cereal grains. Infestations are difficult to control as larvae feed inside grain kernels, and many populations are resistant to both contact insecticides and fumigants. We sequenced the genome of R. dominica to identify genes responsible for important biological functions and develop more targeted and efficacious management strategies. The genome was assembled from long read sequencing and long-range scaffolding technologies. The genome assembly is 479.1 Mb, close to the predicted genome size of 480.4 Mb by flow cytometry. This assembly is among the most contiguous beetle assemblies published to date, with 139 scaffolds, an N50 of 53.6 Mb, and L50 of 4, indicating chromosome-scale scaffolds. Predicted genes from biologically relevant groups were manually annotated using transcriptome data from adults and different larval tissues to guide annotation. The expansion of carbohydrase and serine peptidase genes suggest that they combine to enable efficient digestion of cereal proteins. A reduction in the copy number of several detoxification gene families relative to other coleopterans may reflect the low selective pressure on these genes in an insect that spends most of its life feeding internally. Chemoreceptor genes contain elevated numbers of pseudogenes for odorant receptors that also may be related to the recent ontogenetic shift of R. dominica to a diet consisting primarily of stored grains. Analysis of repetitive sequences will further define the evolution of bostrichid beetles compared to other species. The data overall contribute significantly to coleopteran genetic research.

The World of Pseudogenes: New Diagnostic and Therapeutic Targets in Cancers or Still Mystery Molecules?

Pseudogenes were once considered as “junk DNA”, due to loss of their functions as a result of the accumulation of mutations, such as frameshift and presence of premature stop-codons and relocation of genes to inactive heterochromatin regions of the genome. Pseudogenes are divided into two large groups, processed and unprocessed, according to their primary structure and origin. Only 10% of all pseudogenes are transcribed into RNAs and participate in the regulation of parental gene expression at both transcriptional and translational levels through senseRNA (sRNA) and antisense RNA (asRNA). In this review, about 150 pseudogenes in the different types of cancers were analyzed. Part of these pseudogenes seem to be useful in molecular diagnostics and can be detected in various types of biological material including tissue as well as biological fluids (liquid biopsy) using different detection methods. The number of pseudogenes, as well as their function in the human genome, is still unknown. However, thanks to the development of various technologies and bioinformatic tools, it was revealed so far that pseudogenes are involved in the development and progression of certain diseases, especially in cancer.

Comprehensive Genomic Characterization Analysis Identifies an Oncogenic Pseudogene RP11-3543B.1 in Human Gastric Cancer.

Background: Gastrointestinal Cancer (GICs) is the most common group of malignancies, and many of its types are the leading causes of cancer related death worldwide. Pseudogenes have been revealed to have critical regulatory roles in human cancers. The objective of this study is to comprehensive characterize the pseudogenes expression profiling and identify key pseudogenes in the development of gastric cancer (GC).Methods: The pseudogenes expression profiling was analyzed in six types of GICs cancer from The Cancer Genome Atlas RNA-seq data to identify GICs cancer related pseudogenes. Meanwhile, the genomic characterization including somatic alterations of pseudogenes was analyzed. Then, CCK8 and colony formation assays were performed to evaluate the biological function of RP11-3543B.1 and miR-145 in gastric cancer cells. The mechanisms of pseudogene RP11-3543B.1 in GC cells were explored via using bioinformatics analysis, next generation sequencing and lucifarese reporter assay.Results: We identified a great number of pseudogenes with significantly altered expression in GICs, and some of these pseudogenes expressed differently among the six cancer types. The amplification or deletion in the pseudogenes-containing loci involved in the alterations of pseudogenes expression in GICs. Among these altered pseudogenes, RP11-3543B.1 is significantly upregulated in gastric cancer. Down-regulation of RP11-3543B.1 expression impaired GC cells proliferation both in vitro and in vivo. RP11-3543B.1 exerts oncogene function via targeting miR-145-5p to regulate MAPK4 expression in gastric cancer cells.Conclusion: Our study reveals the potential of pseudogenes expression as a new paradigm for investigating GI cancer tumorigenesis and discovering prognostic biomarkers for patients.

Pseudogenes: Four Decades of Discovery.

A pseudogene is defined as a genomic DNA sequence that looks like a mutated or truncated version of a known functional gene. Nearly four decades since their first discovery it has been estimated that between ~12,000 and~20,000 pseudogenes exist in the human genome. Early efforts to characterize functions for pseudogenes were unsuccessful, thus they were considered functionless relics of evolutionary selection, junk DNA or genetic fossils. Remarkably, an increasing number of pseudogenes have been reported to be expressed as RNA transcripts above and beyond levels considered accidental or spurious transcription. There is emerging evidence that some expressed pseudogene transcripts have biological functions and should be defined as a subclass of functional long noncoding RNAs (lncRNA). In this introductory chapter, I briefly summarize the history and the current knowledge of pseudogenes, and highlight the emerging functions of some pseudogenes in human biology and disease. This second iteration of Pseudogenes in Methods in Molecular Biology highlights new methodological approaches to investigate this intriguing family of lncRNAs and the extent of their biological function.

Pseudogenes as Biomarkers and Therapeutic Targets in Human Cancers.

Pseudogenes are commonly labeled as "junk DNA" given their perceived nonfunctional status. However, the advent of large-scale genomics projects prompted a revisit of pseudogene biology, highlighting their key functional and regulatory roles in numerous diseases, including cancers. Integrative analyses of cancer data have shown that pseudogenes can be transcribed and even translated, and that pseudogenic DNA, RNA, and proteins can interfere with the activity and function of key protein coding genes, acting as regulators of oncogenes and tumor suppressors. Capitalizing on the available clinical research, we are able to get an insight into the spread and variety of pseudogene biomarker and therapeutic potential. In this chapter, we describe pseudogenes that fulfill their role as diagnostic or prognostic biomarkers, both as unique elements and in collaboration with other genes or pseudogenes. We also report that the majority of prognostic pseudogenes are overexpressed and exert an oncogenic role in colorectal, liver, lung, and gastric cancers. Finally, we highlight a number of pseudogenes that can establish future therapeutic avenues.

Multipartite Genome of Lyme Disease Borrelia: Structure, Variation and Prophages.

All members of the Borrelia genus that have been examined harbour a linear chromosome that is about 900 kbp in length, as well as a plethora of both linear and circular plasmids in the 5-220 kbp size range. Genome sequences for 27 Lyme disease Borrelia isolates have been determined since the elucidation of the B. burgdorferi B31 genome sequence in 1997. The chromosomes, which carry the vast majority of the housekeeping genes, appear to be very constant in gene content and organization across all Lyme disease Borrelia species. The content of the plasmids, which carry most of the genes that encode the differentially expressed surface proteins that interact with the spirochete's arthropod and vertebrate hosts, is much more variable. Lyme disease Borrelia isolates carry between 7-21 different plasmids, ranging in size from 5-84 kbp. All strains analyzed to date harbor three plasmids, cp26, lp54 and lp17. The plasmids are unusual, as compared to most bacterial plasmids, in that they contain many paralogous sequences, a large number of pseudogenes, and, in some cases, essential genes. In addition, a number of the plasmids have features indicating that they are prophages. Numerous methods have been developed for Lyme disease Borrelia strain typing. These have proven valuable for clinical and epidemiological studies, as well as phylogenomic and population genetic analyses. Increasingly, these approaches have been displaced by whole genome sequencing techniques. Some correlations between genome content and pathogenicity have been deduced, and comparative whole genome analyses promise future progress in this arena.

Host-Endosymbiont Genome Integration in a Deep-Sea Chemosymbiotic Clam.

Endosymbiosis with chemosynthetic bacteria has enabled many deep-sea invertebrates to thrive at hydrothermal vents and cold seeps, but most previous studies on this mutualism have focused on the bacteria only. Vesicomyid clams dominate global deep-sea chemosynthesis-based ecosystems. They differ from most deep-sea symbiotic animals in passing their symbionts from parent to offspring, enabling intricate coevolution between the host and the symbiont. Here, we sequenced the genomes of the clam Archivesica marissinica (Bivalvia: Vesicomyidae) and its bacterial symbiont to understand the genomic/metabolic integration behind this symbiosis. At 1.52 Gb, the clam genome encodes 28 genes horizontally transferred from bacteria, a large number of pseudogenes and transposable elements whose massive expansion corresponded to the timing of the rise and subsequent divergence of symbiont-bearing vesicomyids. The genome exhibits gene family expansion in cellular processes that likely facilitate chemoautotrophy, including gas delivery to support energy and carbon production, metabolite exchange with the symbiont, and regulation of the bacteriocyte population. Contraction in cellulase genes is likely adaptive to the shift from phytoplankton-derived to bacteria-based food. It also shows contraction in bacterial recognition gene families, indicative of suppressed immune response to the endosymbiont. The gammaproteobacterium endosymbiont has a reduced genome of 1.03 Mb but retains complete pathways for sulfur oxidation, carbon fixation, and biosynthesis of 20 common amino acids, indicating the host’s high dependence on the symbiont for nutrition. Overall, the host–symbiont genomes show not only tight metabolic complementarity but also distinct signatures of coevolution allowing the vesicomyids to thrive in chemosynthesis-based ecosystems.

PgenePapers: a novel database and search tools of reported regulatory pseudogenes

Background: Pseudogenes are non-coding relatives of genes. Recent studies have shown that a considerable number of pseudogenes are transcribed, and some of them can regulate gene expression. Studies have detected pseudogene differential expression in cancer subtypes, indicating potential impact of pseudogenes on cancer development and clinical outcomes. Pseudogenes make a new class of expression modulators. However, there is not yet a database focusing on regulatory roles of pseudogenes. Methods: We constructed the regulatory networks involving pseudogenes and genes with disease and tissue specific annotations, and further included potential miRNAs and drugs targeting components of the networks, based on expression profiles, miRNA binding predictions and FDA approved drugs. Results and conclusion: We developed the first comprehensive database of reported regulatory pseudogenes, and developed the PgenePapers app which allows flexible database search and provides network visualisation. PgenePapers provides a knowledgebase upon which we can develop methods for pseudogene function prediction and validation.

PgenePapers: a novel database and search tools of reported regulatory pseudogenes

Background: Pseudogenes are non-coding relatives of genes. Recent studies have shown that a considerable number of pseudogenes are transcribed, and some of them can regulate gene expression. Studies have detected pseudogene differential expression in cancer subtypes, indicating potential impact of pseudogenes on cancer development and clinical outcomes. Pseudogenes make a new class of expression modulators. However, there is not yet a database focusing on regulatory roles of pseudogenes. Methods: We constructed the regulatory networks involving pseudogenes and genes with disease and tissue specific annotations, and further included potential miRNAs and drugs targeting components of the networks, based on expression profiles, miRNA binding predictions and FDA approved drugs. Results and conclusion: We developed the first comprehensive database of reported regulatory pseudogenes, and developed the PgenePapers app which allows flexible database search and provides network visualisation. PgenePapers provides a knowledgebase upon which we can develop methods for pseudogene function prediction and validation.

Overcoming challenges and dogmas to understand the functions of pseudogenes.

Pseudogenes are defined as regions of the genome that contain defective copies of genes. They exist across almost all forms of life, and in mammalian genomes are annotated in similar numbers to recognized protein-coding genes. Although often presumed to lack function, growing numbers of pseudogenes are being found to play important biological roles. In consideration of their evolutionary origins and inherent limitations in genome annotation practices, we posit that pseudogenes have been classified on a scientifically unsubstantiated basis. We reflect that a broad misunderstanding of pseudogenes, perpetuated in part by the pejorative inference of the 'pseudogene' label, has led to their frequent dismissal from functional assessment and exclusion from genomic analyses. With the advent of technologies that simplify the study of pseudogenes, we propose that an objective reassessment of these genomic elements will reveal valuable insights into genome function and evolution.