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Background: Ticks, hematophagous Acari, pose a significant threat by transmitting various pathogens to their vertebrate hosts during feeding. Despite advances in tick genomics, high-quality genomes were lacking until recently, particularly in the genus Ixodes, which includes the main vectors of Lyme disease. Results: Here, we present the genome sequences of four tick species, derived from a single female individual, with a particular focus on the European species Ixodes ricinus, achieving a chromosome-level assembly. Additionally, draft assemblies were generated for the three other Ixodes species, I. persulcatus, I. pacificus, and I. hexagonus. The quality of the four genomes and extensive annotation of several important gene families have allowed us to study the evolution of gene repertoires at the level of the genus Ixodes and of the tick group. We have determined gene families that have undergone major amplifications during the evolution of ticks, while an expression atlas obtained for I. ricinus reveals striking patterns of specialization both between and within gene families. Notably, several gene family amplifications are associated with a proliferation of single-exon genes—most strikingly for fatty acid elongases and sulfotransferases. Conclusions: The integration of our data with existing genomes establishes a solid framework for the study of gene evolution, improving our understanding of tick biology. In addition, our work lays the foundations for applied research and innovative control targeting these organisms. [ABSTRACT FROM AUTHOR]

Abstract Background Gene duplication is a dominant mechanism for the evolution of genomes and plays a key role in genome expansion. Gene duplication via retroposition produces RNA-mediated intron-less copies called retrocopies, that may gain regulatory sequence and biological function to generate retrogenes. Retrocopies dynamics have been reported in several model insect species, but there is still a huge knowledge gap about retrocopies dynamics in most insects, and their role in adaptation. Results In this study, we reported retrocopy dynamics in 40 species of insect pests of plants belonging to six insect orders. We identified a total of 9,930 retrocopies, which is so far the largest set of retrocopies identified in insects. The identified retrocopies were further grouped into 2,599 Retrogenes, 4,578 Chimeras, 1,241 Intact retrocopies, and 1,512 Pseudogene. We also analyzed all the identified retrogenes that were annotated into 506 gene families. The highest number of retrogenes annotated belong to the heat shock proteins superfamily and are present across all the 40 species from the six orders. We found a significant expansion of the heat shock protein superfamily in the studied species. Almost all the retrogenes, including those belonging to heat shock proteins, are under purifying selection. In summary, we report the retrocopies and retrogenes dynamics in a large set of insect pests of plants and the expansion of the heat shock protein family due to retroposition. Conclusion This study unveils retrocopy dynamics in the insect pests of plants and highlights the evolution of new genes due to retroposition, and their role in important gene families’ expansion.

Background: Gene duplication is a dominant mechanism for the evolution of genomes and plays a key role in genome expansion. Gene duplication via retroposition produces RNA-mediated intron-less copies called retrocopies, that may gain regulatory sequence and biological function to generate retrogenes. Retrocopies dynamics have been reported in several model insect species, but there is still a huge knowledge gap about retrocopies dynamics in most insects, and their role in adaptation. Results: In this study, we reported retrocopy dynamics in 40 species of insect pests of plants belonging to six insect orders. We identified a total of 9,930 retrocopies, which is so far the largest set of retrocopies identified in insects. The identified retrocopies were further grouped into 2,599 Retrogenes, 4,578 Chimeras, 1,241 Intact retrocopies, and 1,512 Pseudogene. We also analyzed all the identified retrogenes that were annotated into 506 gene families. The highest number of retrogenes annotated belong to the heat shock proteins superfamily and are present across all the 40 species from the six orders. We found a significant expansion of the heat shock protein superfamily in the studied species. Almost all the retrogenes, including those belonging to heat shock proteins, are under purifying selection. In summary, we report the retrocopies and retrogenes dynamics in a large set of insect pests of plants and the expansion of the heat shock protein family due to retroposition. Conclusion: This study unveils retrocopy dynamics in the insect pests of plants and highlights the evolution of new genes due to retroposition, and their role in important gene families' expansion. [ABSTRACT FROM AUTHOR]

Dinoflagellates are a remarkable group of protists, not only for their association with harmful algal blooms and coral reefs but also for their numerous characteristics deviating from the rules of eukaryotic biology. Genome research on dinoflagellates has lagged due to their immense genome sizes in most species (~ 1-250 Gbp). Nevertheless, the last decade marked a fruitful era of dinoflagellate genomics, with 27 genomes sequenced and many insights attained. This review aims to synthesize information from these genomes, along with other omic data, to reflect on where we are now in understanding dinoflagellates and where we are heading in the future. The most notable insights from the decade-long genomics work include: (1) dinoflagellate genomes have been expanded in multiple times independently, probably by a combination of rampant retroposition, accumulation of repetitive DNA, and genome duplication; (2) Symbiodiniacean genomes are highly divergent, but share about 3,445 core unigenes concentrated in 219 KEGG pathways; (3) Most dinoflagellate genes are encoded unidirectionally and are not intron-poor; (4) The dinoflagellate nucleus has undergone extreme evolutionary changes, including complete or nearly complete loss of nucleosome and histone H1, and acquisition of dinoflagellate viral nuclear protein (DVNP); (5) Major basic nuclear protein (MBNP), histone-like protein (HLP), and bacterial HU-like protein (HCc) belong to the same protein family, and MBNP can be the unifying name; (6) Dinoflagellate gene expression is regulated by poorly understood mechanisms, but microRNA and other epigenetic mechanisms are likely important; (7) Over 50% of dinoflagellate genes are "dark" and their functions remain to be deciphered using functional genetics; (8) Initial insights into the genomic basis of parasitism and mutualism have emerged. The review then highlights functionally unique and interesting genes. Future research needs to obtain a finished genome, tackle large genomes, characterize the unknown genes, and develop a quantitative molecular ecological model for addressing ecological questions. [ABSTRACT FROM AUTHOR]

Gene duplication is the process of a gene copied via specific molecular mechanisms to form more duplicate genes. As an important approach to the origination of new genes, gene duplication contributes to around half of the genes in eukaryotic genomes, facilitating the adaptive evolution of species. Over the past fifty years, especially since entering the genomics era in the last two decades, there have been extensive and profound discussions on the mechanisms, evolutionary processes and forces behind the emergence of duplicate genes. Sequence similarity of duplicate genes often leads to functional redundancy, enhancing organismal robustness. Conversely, functional divergence can create novel functions and improve evolvability. In this review, we summarize the mechanism of gene duplication, the fate and the evolutionary models of duplicate genes. This article concludes by outlining how long-read sequencing technologies, gene editing, and various other high-throughput techniques will further advance our understanding of the role of duplicate genes in the genetics-development-evolution network.

Genes that originate during evolution are an important source of novel biological functions. Retrogenes are functional copies of genes produced by retroduplication and as such are located in different genomic positions. To investigate retroposition patterns and retrogene expression, we computationally identified interchromosomal retroduplication events in nine portions of the phylogenetic history of malaria mosquitoes, making use of species that do or do not have classical sex chromosomes to test the roles of sex-linkage. We found 40 interchromosomal events and a significant excess of retroduplications from the X chromosome to autosomes among a set of young retrogenes. These young retroposition events occurred within the last 100 million years in lineages where all species possessed differentiated sex chromosomes. An analysis of available microarray and RNA-seq expression data for Anopheles gambiae showed that many of the young retrogenes evolved male-biased expression in the reproductive organs. Young autosomal retrogenes with increased meiotic or postmeiotic expression in the testes tend to be male biased. In contrast, older retrogenes, i.e., in lineages with undifferentiated sex chromosomes, do not show this particular chromosomal bias and are enriched for female-biased expression in reproductive organs. Our reverse-transcription PCR data indicates that most of the youngest retrogenes, which originated within the last 47.6 million years in the subgenus Cellia, evolved non-uniform expression patterns across body parts in the males and females of An. coluzzii. Finally, gene annotation revealed that mitochondrial function is a prominent feature of the young autosomal retrogenes. We conclude that mRNA-mediated gene duplication has produced a set of genes that contribute to mosquito reproductive functions and that different biases are revealed after the sex chromosomes evolve. Overall, these results suggest potential roles for the evolution of meiotic sex chromosome inactivation in males and of sexually antagonistic conflict related to mitochondrial energy function as the main selective pressures for X-to-autosome gene reduplication and testis-biased expression in these mosquito lineages. [ABSTRACT FROM AUTHOR]

Retroduplication variation (RDV), a type of retrocopy polymorphism, is considered to have essential biological significance, but its effect on gene function and species phenotype is still poorly understood. To this end, we analyzed the retrocopies and RDVs in 3,010 rice genomes. We calculated the RDV frequencies in the genome of each rice population; detected the mutated, ancestral and expressed retrogenes in rice genomes; and analyzed their RDV influence on rice phenotypic traits. Collectively, 73 RDVs were identified, and 14 RDVs in ancestral retrogenes can significantly affect rice phenotypes. Our research reveals that RDV plays an important role in rice migration, domestication and evolution. We think that RDV is a good molecular breeding marker candidate. To our knowledge, this is the first study on the relationship between retrogene function, expression, RDV and species phenotype.

The major advantage of mRNA vaccines over more conventional approaches is their potential for rapid development and large-scale deployment in pandemic situations. In the current COVID-19 crisis, two mRNA COVID-19 vaccines have been conditionally approved and broadly applied, while others are still in clinical trials. However, there is no previous experience with the use of mRNA vaccines on a large scale in the general population. This warrants a careful evaluation of mRNA vaccine safety properties by considering all available knowledge about mRNA molecular biology and evolution. Here, I discuss the pervasive claim that mRNA-based vaccines cannot alter genomes. Surprisingly, this notion is widely stated in the mRNA vaccine literature but never supported by referencing any primary scientific papers that would specifically address this question. This discrepancy becomes even more puzzling if one considers previous work on the molecular and evolutionary aspects of retroposition in murine and human populations that clearly documents the frequent integration of mRNA molecules into genomes, including clinical contexts. By performing basic comparisons, I show that the sequence features of mRNA vaccines meet all known requirements for retroposition using L1 elements—the most abundant autonomously active retrotransposons in the human genome. In fact, many factors associated with mRNA vaccines increase the possibility of their L1-mediated retroposition. I conclude that is unfounded to a priori assume that mRNA-based therapeutics do not impact genomes and that the route to genome integration of vaccine mRNAs via endogenous L1 retroelements is easily conceivable. This implies that we urgently need experimental studies that would rigorously test for the potential retroposition of vaccine mRNAs. At present, the insertional mutagenesis safety of mRNA-based vaccines should be considered unresolved. [ABSTRACT FROM AUTHOR]

Abstract Background The huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington’s disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT. Results We found that in amniotes HAP40 is encoded by a single-exon gene, whereas in all other organisms it is expressed from multi-exon genes. HAP40 co-occurs with HTT in unikonts, including filastereans such as Capsaspora owczarzaki and the amoebozoan Dictyostelium discoideum, but both proteins are absent from fungi. Outside unikonts, a few species, such as the free-living amoeboflagellate Naegleria gruberi, contain putative HTT and HAP40 orthologs. Biochemically we show that the interaction between HTT and HAP40 extends to fish, and bioinformatic analyses provide evidence for evolutionary conservation of this interaction. The closest homologue of HAP40 in current protein databases is the family of soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs). Conclusion Our results indicate that the transition from a multi-exon to a single-exon gene appears to have taken place by retroposition during the divergence of amphibians and amniotes, followed by the loss of the parental multi-exon gene. Furthermore, it appears that the two proteins probably originated at the root of eukaryotes. Conservation of the interaction between HAP40 and HTT and their likely coevolution strongly indicate functional importance of this interaction.

Abstract Background Nicotinic acetylcholine receptors (nAChRs) are among the oldest and most conserved transmembrane receptors involved in signal transduction. Despite the prevalence and significance of cholinergic signaling, the diversity and evolution of nAChRs are not fully understood. Result By comparative genomic analysis, we found massive expansions of nAChR genes in molluscs and some other lophotrochozoans. The expansion is particularly pronounced in stationary bivalve molluscs with simple nervous systems, with the number of nAChR genes ranging from 99 to 217 in five bivalves, compared with 10 to 29 in five ecdysozoans and vertebrates. The expanded molluscan nAChR genes tend to be intronless and in tandem arrays due to retroposition followed by tandem duplication. Phylogenetic analysis revealed diverse nAChR families in the common ancestor of bilaterians, which subsequently experienced lineage-specific expansions or contractions. The expanded molluscan nAChR genes are highly diverse in sequence, domain structure, temporal and spatial expression profiles, implying diversified functions. Some molluscan nAChR genes are expressed in early development before the development of the nervous system, while others are involved in immune and stress responses. Conclusion The massive expansion and diversification of nAChR genes in bivalve molluscs may be a compensation for reduced nervous systems as part of adaptation to stationary life under dynamic environments, while in vertebrates a subset of specialized nAChRs are retained to work with advanced nervous systems. The unprecedented diversity identified in molluscs broadens our view on the evolution and function of nAChRs that are critical to animal physiology and human health.

Gene duplication occurs by either DNA- or RNA-based processes; the latter duplicates single genes via retroposition of messenger RNA. The expression of a retroposed gene copy (retrocopy) is expected to be uncorrelated with its source gene because upstream promoter regions are usually not part of the retroposition process. In contrast, DNA-based duplication often encompasses both the coding and the intergenic (promoter) regions; hence, expression is often correlated, at least initially, between DNA-based duplicates. In this study, we identified 150 retrocopies in rice (Oryza sativa L. ssp japonica), most of which represent ancient retroposition events. We measured their expression from high-throughput RNA sequencing (RNAseq) data generated from seven tissues. At least 66% of the retrocopies were expressed but at lower levels than their source genes. However, the tissue specificity of retrogenes was similar to their source genes, and expression between retrocopies and source genes was correlated across tissues. The level of correlation was similar between RNA- and DNA-based duplicates, and they decreased over time at statistically indistinguishable rates. We extended these observations to previously identified retrocopies in Arabidopsis thaliana, suggesting they may be general features of the process of retention of plant retrogenes.

Background: The huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington's disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT. Results: We found that in amniotes HAP40 is encoded by a single-exon gene, whereas in all other organisms it is expressed from multi-exon genes. HAP40 co-occurs with HTT in unikonts, including filastereans such as Capsaspora owczarzaki and the amoebozoan Dictyostelium discoideum, but both proteins are absent from fungi. Outside unikonts, a few species, such as the free-living amoeboflagellate Naegleria gruberi, contain putative HTT and HAP40 orthologs. Biochemically we show that the interaction between HTT and HAP40 extends to fish, and bioinformatic analyses provide evidence for evolutionary conservation of this interaction. The closest homologue of HAP40 in current protein databases is the family of soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs). Conclusion: Our results indicate that the transition from a multi-exon to a single-exon gene appears to have taken place by retroposition during the divergence of amphibians and amniotes, followed by the loss of the parental multi-exon gene. Furthermore, it appears that the two proteins probably originated at the root of eukaryotes. Conservation of the interaction between HAP40 and HTT and their likely coevolution strongly indicate functional importance of this interaction. [ABSTRACT FROM AUTHOR]

Retroposition is RNA-based gene duplication leading to the creation of single exon nonfunctional copies. Nevertheless, over time, many of these duplicates acquire transcriptional capabilities. In human in most cases, these so-called retrogenes do not code for proteins but function as regulatory long noncoding RNAs (lncRNAs). The mechanisms by which they can regulate other genes include microRNA sponging, modulation of alternative splicing, epigenetic regulation and competition for stabilizing factors, among others. Here, we summarize recent findings related to lncRNAs originating from retrocopies that are involved in human diseases such as cancer and neurodegenerative, mental or cardiovascular disorders. Special attention is given to retrocopies that regulate their progenitors or host genes. Presented evidence from the literature and our bioinformatics analyses demonstrates that these retrocopies, often described as unimportant pseudogenes, are significant players in the cell’s molecular machinery.

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis.

The birth and evolution of retrogenes have played crucial roles in genome evolution. Dinoflagellates represent a unique lineage for retrogene research because the retrogenes can be reliably identified by the presence of a 22 nucleotide splice leader called DinoSL, which is post-transcriptionally added to the 5′ terminus of all mRNAs. Compared to studies of retrogenes conducted in other model genomes, dinoflagellate retrogenes can potentially be more comprehensively characterized because intron-containing retrogenes have already been detected. Unfortunately, dinoflagellate retrogene research has long been neglected. Here, we review the work on dinoflagellate retrogenes and show their distinct character. Like the dinoflagellate genome itself, dinoflagellate retrogenes are also characterized by many unusual features, including a high survival rate and large numbers in the genome. These data are critical complements to what we know about retrogenes, and will further frame our understanding of retroposition and its roles in genome evolution, as well as providing new insights into retrogene studies in other genomes.

Proliferating cell nuclear antigen (PCNA) plays critical roles in eukaryotic DNA replication and replication‐associated processes. It is typically encoded by one or two gene copies (pcna) in eukaryotic genomes. Recently reported higher copy numbers of pcna in some dinoflagellates raised a question of how this gene has uniquely evolved in this phylum. Through real‐time PCR quantification, we found a wide range of pcna copy number (2–287 copies) in 11 dinoflagellate species (n = 38), and a strong positive correlation between pcna copy number and genome size (log10–log10 transformed). Intraspecific pcna diverged up to 21% and are dominated by nonsynonymous substitutions, indicating strong purifying selection pressure on and hence functional necessity of this gene. By surveying pcna copy numbers in eukaryotes, we observed a genome size threshold at 4 pg DNA, above which more than two pcna copies are found. To examine whether retrotransposition is a mechanism of pcna duplication, we measured the copy number of retroposed pcna, taking advantage of the 22‐nt dinoflagellate‐specific spliced leader (DinoSL) capping the 5′ end of dinoflagellate nuclear‐encoded mRNAs, which would exist in the upstream region of a retroposed gene copy. We found that retroposed pcna copy number increased with total pcna copy number and genome size. These results indicate co‐evolution of dinoflagellate pcna copy number with genome size, and retroposition as a major mechanism of pcna duplication in dinoflagellates. Furthermore, we posit that the demand of faithful replication and maintenance of the large dinoflagellate genomes might have favored the preservation of the retroposed pcna as functional genes. [ABSTRACT FROM AUTHOR]

Summary: Ubiquitin (Ub) and Ub‐like proteins, collectively forming the ubiquiton family, regulate nearly all aspects of cellular processes via post‐translational modifications. Studies devoted to specific members suggested a large expansion of this family in plants; however, a lack of systematic analysis hinders the comparison of individual members at both evolutionary history and functional divergence levels, which may provide new insight into biological functions. In this work, we first retrieved a total of 5856 members of 17 known ubiquiton subfamilies in 50 plant genomes by searching both prior annotations and missing loci in each genome. We then applied this list to analyze the duplication history of major ubiquiton subfamilies in plants. We show that autophagy‐related protein 8 (ATG8), membrane‐anchored Ub‐fold (MUB), small Ub‐like modifier (SUMO) and Ub loci encode 88% of the plant ubiquiton family. Although whole genome duplications (WGDs) significantly expanded the family, we discovered contrasting duplication patterns both in species and in subfamilies. Within the family, the ATG8 and MUB members were primarily duplicated through WGDs, whereas a significant number of Ub and SUMO loci were generated through retroposition and tandem duplications, respectively. Although Ub coding regions are highly conserved in plants, promoter activity analysis demonstrated lineage‐specific expression patterns of polyUb genes in Oryza sativa (rice) and Arabidopsis, confirming their retroposition origin. Based on the theory of dosage balance constraints, our study suggests that ubiquiton members duplicated through WGDs play crucial roles in plants, and that the regulatory pathways involving ATG8 and MUB are more conserved than those controlled by Ub and SUMO. [ABSTRACT FROM AUTHOR]

The birth and evolution of retrogenes have played crucial roles in genome evolution. Dinoflagellates represent a unique lineage for retrogene research because the retrogenes can be reliably identified by the presence of a 22 nucleotide splice leader called DinoSL, which is post-transcriptionally added to the 5′ terminus of all mRNAs. Compared to studies of retrogenes conducted in other model genomes, dinoflagellate retrogenes can potentially be more comprehensively characterized because intron-containing retrogenes have already been detected. Unfortunately, dinoflagellate retrogene research has long been neglected. Here, we review the work on dinoflagellate retrogenes and show their distinct character. Like the dinoflagellate genome itself, dinoflagellate retrogenes are also characterized by many unusual features, including a high survival rate and large numbers in the genome. These data are critical complements to what we know about retrogenes, and will further frame our understanding of retroposition and its roles in genome evolution, as well as providing new insights into retrogene studies in other genomes. [ABSTRACT FROM AUTHOR]

Background: Retroposition, one of the processes of copying the genetic material, is an important RNA-mediated mechanism leading to the emergence of new genes. Because the transcription controlling segments are usually not copied to the new location in this mechanism, the duplicated gene copies (retrocopies) become pseudogenized. However, few can still survive, e.g. by recruiting novel regulatory elements from the region of insertion. Subsequently, these duplicated genes can contribute to the formation of lineage-specific traits and phenotypic diversity. Despite the numerous studies of the functional retrocopies (retrogenes) in animals and plants, very little is known about their presence in green algae, including morphologically diverse species. The current availability of the genomes of both uni- and multicellular algae provides a good opportunity to conduct a genome-wide investigation in order to fill the knowledge gap in retroposition phenomenon in this lineage. Results: Here we present a comparative genomic analysis of uni- and multicellular algae, Chlamydomonas reinhardtii and Volvox carteri, respectively, to explore their retrogene complements. By adopting a computational approach, we identified 141 retrogene candidates in total in both genomes, with their fraction being significantly higher in the multicellular Volvox. Majority of the retrogene candidates showed signatures of functional constraints, thus indicating their functionality. Detailed analyses of the identified retrogene candidates, their parental genes, and homologs of both, revealed that most of the retrogene candidates were derived from ancient retroposition events in the common ancestor of the two algae and that the parental genes were subsequently lost from the respective lineages, making many retrogenes 'orphan'. Conclusion: We revealed that the genomes of the green algae have maintained many possibly functional retrogenes in spite of experiencing various molecular evolutionary events during a long evolutionary time after the retroposition events. Our first report about the retrogene set in the green algae provides a good foundation for any future investigation of the repertoire of retrogenes and facilitates the assessment of the evolutionary impact of retroposition on diverse morphological traits in this lineage. [ABSTRACT FROM AUTHOR]

Previous studies of the function and evolution of retrocopies in plants, Drosophila and non-mammalian chordates provided new insights into the origin of novel genes. However, little is known about retrocopies and their parental genes in teleosts, and it remains obscure whether there is any correlation between them. The present study aimed to characterize the spatial and temporal expression profiles of retrogenes and their parental genes based on RNA-Seq data from Danio rerio embryos and tissues from adult. Using a modified pipeline, 306 retrocopies were identified in the zebrafish genome, most of which exhibited ancient retroposition, and 76 of these showed a Ks < 2.0. Expression of a retrocopy is generally expected to present no correlation with its parental gene, as regulatory regions are not part of the retroposition event. Here, this assumption was tested based on RNA-Seq data from eight stages and thirteen tissue types of zebrafish. However, the result suggested that retrocopies displayed correlated expression with their parental genes. The level of correlation was found to decrease during embryogenesis, but to increase slightly within a tissue using Ks as the proxy for the divergence time. Tissue specificity was also observed: retrocopies were found to be expressed at a more specific level compared with their parental genes. Unlike Drosophila, which has sex chromosomes, zebrafish do not show testis-biased expression. Our study elaborated temporal and spatial patterns of expression of retrocopies in zebrafish, examined the correlation between retrocopies and parental genes and analyzed potential source of regulated elements of retrocopies, which lay a foundation for further functional study of retrocopies. [ABSTRACT FROM AUTHOR]

Freed from the competition of large raptors, Paleocene carnivores could expand their newly acquired habitats in search of prey. Such changing conditions might have led to their successful distribution and rapid radiation. Today, molecular evolutionary biologists are faced, however, with the consequences of such accelerated adaptive radiations, because they led to sequential speciation more rapidly than phylogenetic markers could be fixed. The repercussions being that current genealogies based on such markers are incongruent with species trees. Our aim was to explore such conflicting phylogenetic zones of evolution during the early arctoid radiation, especially to distinguish diagnostic from misleading phylogenetic signals, and to examine other carnivore-related speciation events. We applied a combination of high-throughput computational strategies to screen carnivore and related genomes in silico for randomly inserted retroposed elements that we then used to identify inconsistent phylogenetic patterns in the Arctoidea group, which is well known for phylogenetic discordances. Our combined retrophylogenomic and in vitro wet lab approach detected hundreds of carnivore-specific insertions, many of them confirming well-established splits or identifying and solving conflicting species distributions. Our systematic genome-wide screens for Long INterspersed Elements detected homoplasy-free markers with insertion-specific truncation points that we used to distinguish phylogenetically informative markers from conflicting signals. The results were independently confirmed by phylogenetic diagnostic Short INterspersed Elements. As statistical analysis ruled out ancestral hybridization, these doubly verified but still conflicting patterns were statistically determined to be genomic remnants from a time of ancestral incomplete lineage sorting that especially accompanied large parts of Arctoidea evolution. [ABSTRACT FROM AUTHOR]

Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution. [ABSTRACT FROM PUBLISHER]

Highlights: [•] Cercospora spp. harbor MAT gene fragments at random locations in the genome. [•] MAT fragments reconstituted MAT exons with high identity when manually assembled. [•] MAT fragmentation pattern suggests fused MAT genes in homothallic ancestor. [•] Concerted evolution homogenized MAT fragments and MAT genes in each species. [Copyright &y& Elsevier]

Highlights: [•] Two burst of retropositions were found during primate evolution. [•] Approximately 10% intact retrocopies (potential functional genes) may be under positive selection. [•] Over 4% retrocopies eventually become functional after their origination. [•] Human intact retrocopies are enriched for functions involved in transcription. [ABSTRACT FROM AUTHOR]

The major problem with removable functional appliance is that a large amount of patient co-operation is required. The efficacy of the removable Twin Block (RTB) appliance (and its modifications) has already been proved by many workers. A major drawback of this appliance is patient compliance, therefore, the aim of this study was to evaluate the effectiveness of a fixed twin block appliance (bonded type) in subjects who reported during the last phases of skeletal growth with a Class II skeletal pattern. A six month cross-sectional prospective cohort study was conducted with a sample size of 20 subjects (9 males and 11 females). Evaluation of the changes in the profile view using clinical and cephalometrical findings were carried out. Appliance was found to be effective and useful for correction of retropositioned lower jaw, specially during the circumpubertal growth spurts in both sexes. [ABSTRACT FROM AUTHOR]

Gene duplication occurs by either DNA- or RNA-based processes; the latter duplicates single genes via retroposition of messenger RNA. The expression of a retroposed gene copy (retrocopy) is expected to be uncorrelated with its source gene because upstream promoter regions are usually not part of the retroposition process. In contrast, DNA-based duplication often encompasses both the coding and the intergenic (promoter) regions; hence, expression is often correlated, at least initially, between DNA-based duplicates. In this study, we identified 150 retrocopies in rice (Oryza sativa L. ssp japonica), most of which represent ancient retroposition events. We measured their expression from high-throughput RNA sequencing (RNAseq) data generated from seven tissues. At least 66% of the retrocopies were expressed but at lower levels than their source genes. However, the tissue specificity of retrogenes was similar to their source genes, and expression between retrocopies and source genes was correlated across tissues. The level of correlation was similar between RNA- and DNA-based duplicates, and they decreased over time at statistically indistinguishable rates. We extended these observations to previously identified retrocopies in Arabidopsis thaliana, suggesting they may be general features of the process of retention of plant retrogenes. [ABSTRACT FROM AUTHOR]

Abstract: New gene origination is a fundamental process underlying evolution of biological diversity. Although new genes usually evolve rapidly in sequences, structure and expression, the evolutionary pattern of alternative splicing (AS) in new genes and the molecular mechanisms involved in this alternation remain to be explored. Here, we used the new genes identified in the Drosophila melanogaster lineage to study alternation of AS and the possible functional consequences of these genes. We found that new genes tended to exhibit low degree of AS, though a few new genes were alternatively spliced. Interestingly loss of introns in retroposed new genes can only account for one third of the low-level AS in new genes, while partial gene duplication without AS exons and mutations in the duplicated AS exons/introns together have resulted in two-third AS losses in new genes, indicating that reducing the degree of AS is a general trend in all categories of new genes. Further investigations on tissue expression patterns of these new genes showed that those with AS alternation had a relatively lower expression level, were expressed in fewer tissues and tended to be more likely expressed in testis than their parental genes. All these observations imply that these new genes may have gained diverged structures and expression patterns from their parental genes after AS alternation. [ABSTRACT FROM AUTHOR]

While once almost synonymous, there is an increasing gap between the expanding definition of what constitutes a gene and the conservative and narrowly defined terms code or coding, which for a long time, almost exclusively constituted the open reading frame. Much confusion results from this disparity, especially in light of the plethora of noncoding RNAs (more correctly termed “non-protein-coding RNAs”) that usually are encoded and transcribed by their own genes. A simple solution would be to adopt Ed Trifonov's less constrained definition of a code as any sequence pattern that can have a biological function. Such consideration favors not only a more complex view of the gene as an entity composed of many more or less conserved subgenic modules, but also a concept of modular evolution of genes and entire genomes. [ABSTRACT FROM AUTHOR]

Recent literature demonstrates that retrogenes tend to leave the X chromosome and integrate onto the autosomes and evolve male-biased expression patterns. Several selection-based evolutionary mechanisms have been proposed to explain this observation. Testing these selection-based models requires examining the evolutionary history and functional properties of new retrogenes, particularly those that show evidence of directional movement between the X and the autosomes (X-related retrogenes). This includes autosomal retrogenes with parental paralogs on the X chromosome (X-derived autosomal retrogenes) and those retrogenes integrated onto the X chromosomes (X-linked retrogenes). In order to understand why retrogenes tend to move nonrandomly in genomes, we examined the expression patterns and evolutionary mechanisms concerning gene pairs having young retrogenes—originating less than 20 MYA (after mouse–rat split). We demonstrate that these X-derived autosomal retrogenes evolved a more restricted male-biased expression pattern: they are expressed exclusively or predominantly in the testis, in particular, during the late stages of spermatogenesis. In contrast, the parental counterparts have relatively broad expression patterns in various tissues and spermatogenetic stages. We further observed that positive selection is targeting these X-derived autosomal retrogenes with novel male-biased expression patterns. This suggests that such retrogenes evolved new male germ-line functions that may be complementary to the functions of the parental paralogs, which themselves contribute little during spermatogenesis. Such evolutionary changes may be beneficial to the populations. Furthermore, most identified X-related retrogenes have recruited novel adjacent sequences as their untranslated regions (UTRs), suggesting that these UTRs, acquired de novo, may play an important role in establishing new regulatory mechanisms to carry out the new male germ-line functions. [ABSTRACT FROM PUBLISHER]

Gene duplication plays important roles in organismal evolution, because duplicate genes provide raw materials for the evolution of mechanisms controlling physiological and/or morphological novelties. Gene duplication can occur via several mechanisms, including segmental duplication, tandem duplication and retroposition. Although segmental and tandem duplications have been found to be important for the expansion of a number of multigene families, the contribution of retroposition is not clear. Here we show that plant SKP1 genes have evolved by multiple duplication events from a single ancestral copy in the most recent common ancestor (MRCA) of eudicots and monocots, resulting in 19 ASK ( rabidopsis P1-like) and 28 OSK ( ryza P1-like) genes. The estimated birth rates are more than ten times the average rate of gene duplication, and are even higher than that of other rapidly duplicating plant genes, such as type I MADS box genes, R genes, and genes encoding receptor-like kinases. Further analyses suggest that a relatively large proportion of the duplication events may be explained by tandem duplication, but few, if any, are likely to be due to segmental duplication. In addition, by mapping the gain/loss of a specific intron on gene phylogenies, and by searching for the features that characterize retrogenes/retrosequences, we show that retroposition is an important mechanism for expansion of the plant SKP1 gene family. Specifically, we propose that two and three ancient retroposition events occurred in lineages leading to Arabidopsis and rice, respectively, followed by repeated tandem duplications and chromosome rearrangements. Our study represents a thorough investigation showing that retroposition can play an important role in the evolution of a plant gene family whose members do not encode mobile elements. [ABSTRACT FROM AUTHOR]

To systematically estimate the gene duplication events in closely related species, we have to use comparative genomic approaches, either through genomic sequence comparison or comparative genomic hybridization (CGH). Given the scarcity of complete genomic sequences of plant species, in the present study we adopted an array based CGH to investigate gene duplications in the genus Arabidopsis. Fragment genomic DNA from four species, namely Arabidopsis thaliana, A. lyrata subsp. lyrata, A. lyrata subsp. petraea, and A. halleri, was hybridized to Affymetrix (Santa Clara, CA, USA) tiling arrays that are designed from the genomic sequences of A. thaliana. Pairwise comparisons of signal intensity were made to infer the potential duplicated candidates along each phylo-genetic branch. Ninety-four potential candidates of gene duplication along the genus were identified. Among them, the majority (69 of 94) were A. thaliana lineage specific. This result indicates that the array based CGH approach may be used to identify candidates of duplication in other plant genera containing closely related species, such as Oryza, particularly for the AA genome species. We compared the degree of gene duplication through retrotransposon between O. sativa and A. thaliana and found a strikingly higher number of chimera retroposed genes in rice. The higher rate of gene duplication through retroposition and other mechanisms may indicate that the grass species is able to adapt to more diverse environments. [ABSTRACT FROM AUTHOR]

Inferences about the evolutionary impact of gene duplications often rely on the analysis of their long-term outcome. The fate of the majority of them must, however, be decided shortly after duplication. Here we analysed the evolutionary pattern of 10 mouse genes very recently duplicated by retrotransposition, by sequencing the retroposed copy in five to 10 closely related mouse species. In all cases the retroposed copy experienced accelerated nonsynonymous evolution whereas the divergence pattern of the source copy appeared unaffected by the duplication, consistent with the neofunctionalization model. The analysis further revealed that most retrogenes, including pseudogenes, did not experience a period of relaxed neutral evolution, but have been submitted to purifying selection ever since their retroposition. We propose that these duplicates play a biochemical role but are not indispensable. Purifying selection prevents them from acquiring a negative role until they are lost or silenced. This period of unnecessary redundancy could in rare cases give the time for new functions to evolve. [ABSTRACT FROM AUTHOR]

A genomic pattern of new gene origination is often dependent on a genomic method that can efficiently identify a statistically adequate number of recently originated genes. The heterochromatic regions have often been viewed as genomic deserts with low coding potential and thus a low flux of new genes. However, increasing reports revealed unexpected roles of heterochromatic regions in the evolution of genes and genomes. We identified recently retroposed genes that originated in heterochromatic regions in Drosophila, by developing microarray-based comparative genomic hybridization (CGH) with multiple species. This new gene family, named Ifc-2h, originated in the common ancestor of the clade of D. simulans, D. mauritiana, and D. sechellia. The sequence features and phylogenetic distribution indicated that Ifc-2h resulted from the retroposition from its parental gene, Infertile crescent ( Ifc), and integrated into heterochromatic region of common ancester of the three sibling species 2 million years ago. Expression analysis revealed that Ifc-2h had developed a new expression pattern by recruiting a putative regulatory element from its target sequence. The distribution of indel variation in Ifc-2h of D. simulans and D. mauritiana revealed a significant sequence constraint, suggesting that the Ifc-2h gene may be functional. These analyses cast fresh insight into the evolution of heterochromatin and the origin of its coding regions. [ABSTRACT FROM AUTHOR]

Abstract: Segmental duplications (SDs) play a key role in genome evolution by providing material for gene diversification and creation of variant or novel functions. They also mediate recombinations, resulting in microdeletions, which have occasionally been associated with human genetic diseases. Here, we present a detailed analysis of a large genomic region (about 240 kb), located on human chromosome 1q22, that contains a tandem SD, SD1q22. This duplication occurred about 37 million years ago in a lineage leading to anthropoid primates, after their separation from prosimians but before the Old and New World monkey split. We reconstructed the hypothetical unduplicated ancestral locus and compared it with the extant SD1q22 region. Our data demonstrate that, as a consequence of the duplication, new anthropoid-specific genetic material has evolved in the resulting paralogous segments. We describe the emergence of two new genes, whose new functions could contribute to the speciation of anthropoid primates. Moreover, we provide detailed information regarding structure and evolution of the SD1q22 region that is a prerequisite for future studies of its anthropoid-specific functions and possible linkage to human genetic disorders. [Copyright &y& Elsevier]

Two release factors (eRF1 and eRF3) are responsible for correct termination of translation in eukaryotes. While the structure and functions of different domains of eRF1 have been sufficiently characterized, the role of eRF3 in translation termination remains unclear. Moreover, the N-terminal domain of eRF3, which is dispensable for termination, is highly divergent. Mammalian eRF3 exists in two isotypes, eRF3a and eRF3b, encoded by genes GSPT1 and GSPT2, respectively. Here we propose that GSPT2 originated through retrotransposition of processed GSPT1 transcript into the genome. Comparison of the 5' non-coding sequences of both genes revealed existence of potential promoter element in 5'UTR of GSPT1 which we suppose to be responsible for GSPT2 transcription. iubmb Life , 58: 199–202, 2006 [ABSTRACT FROM AUTHOR]

Abstract: YY2 was originally identified due to its unusual similarity to the evolutionarily well-conserved zinc finger gene YY1. In this study, we have determined the evolutionary origin and conservation of YY2 using comparative genomic approaches. Our results indicate that YY2 is a retroposed copy of YY1 that has been inserted into another gene locus named Mbtps2 (membrane-bound transcription factor protease site 2). This retroposition is estimated to have occurred after the divergence of placental mammals from other vertebrates based on the detection of YY2 only in the placental mammals. The N- and C-terminal regions of YY2 have evolved under different selection pressures. The N-terminal region has evolved at a very fast pace with very limited functional constraints, whereas the DNA-binding, C-terminal region still maintains a sequence structure very similar to that of YY1 and is also well conserved among placental mammals. In situ hybridizations using different adult mouse tissues indicate that mouse YY2 is expressed at relatively low levels in Purkinje and granular cells of cerebellum and in neuronal cells of cerebrum, but at very high levels in testis. The expression levels of YY2 are much lower than those of YY1, but the overall spatial expression patterns are similar to those of Mbtps2, suggesting a possible shared transcriptional control between YY2 and Mbtps2. Taken together, the formation and evolution of YY2 represent a very unusual case where a transcription factor was first retroposed into another gene locus encoding a protease and survived with different selection schemes and expression patterns. [Copyright &y& Elsevier]

Given that retroposed copies of genes are presumed to lack the regulatory elements required for their expression, retroposition has long been considered a mechanism without functional relevance. However, through an in silico assay for transcriptional activity, we identify here >1,000 transcribed retrocopies in the human genome, of which at least ≈120 have evolved into bona fide genes. Among these, ≈50 retrogenes have evolved functions in testes, more than half of which were recruited as functional autosomal counterparts of X-linked genes during spermatogenesis. Generally, retrogenes emerge ‘out of the testis,’ because they are often initially transcribed in testis and later evolve stronger and sometimes more diverse spatial expression patterns. We find a significant excess of transcribed retrocopies close to other genes or within introns, suggesting that retrocopies can exploit the regulatory elements and/or open chromatin of neighboring genes to become transcribed. In direct support of this hypothesis, we identify 36 retrocopy-host gene fusions, including primate-specific chimeric genes. Strikingly, 27 intergenic retrogenes have acquired untranslated exons de novo during evolution to achieve high expression levels. Notably, our screen for highly transcribed retrocopies also uncovered a retrogene linked to a human recessive disorder, gelatinous drop-like corneal dystrophy, a form of blindness. These functional implications for retroposition notwithstanding, we find that the insertion of retrocopies into genes is generally deleterious, because it may interfere with the transcription of host genes. Our results demonstrate that natural selection has been fundamental in shaping the retrocopy repertoire of the human genome. [ABSTRACT FROM AUTHOR]

In eukaryotes, the primary components of the ribosome are encoded by multicopy nuclear ribosomal RNA (rRNA) genes: 28/265, 185 5.85, and 55. Copies of these genes are typically localized within tandem arrays and homogenized within a genome. As a result, nuclear rRNA gene families have become a paradigm of concerted evolution. In filamentous fungi of the subphylum Pezizomycotina, 55 rRNA genes exist as a large and dispersed multigene family, with between 50 and 100 copies per genome. To determine whether these genes defy the concerted evolution paradigm, we examined the patterns of evolution of these genes by using sequences from the complete genomes of four species. Analyses of these sequences revealed (i) multiple 55 gene types within a genome, (ii) interspecies clustering of gene types, (110 multiple identical gene types shared among species, (iv) multiple pseudogenes within a genome, and (v) presence/absence variation of individual 55 copies in comparisons of closely related species. These results demonstrate that the 55 family in these species is characterized by birth-and-death evolution under strong purifying selection. Furthermore, our results suggest that birth-and-death evolution occurs at different rates in the genera examined, and that the multiplication and movement of 55 genes across the genome are highly dynamic. As such, we hypothesize that a mechanism resembling retroposition controls 55 rRNA gene amplification, dispersal, and integration in the genomes of filamentous fungi. [ABSTRACT FROM AUTHOR]

OXCT/SCOT is the rate-determining enzyme in ketolysis in mitochondria of many extrahepatic organs. Two testicular isoforms, Oxct2a and Oxct2b, are highly homologous and specifically expressed in haploid spermatids of the mouse. In this report, we analyzed the structure and evolution of Oxct2a and Oxct2b. Both Oxct2''s are single-copy intronless genes, of which nucleotide sequences are conserved with Oxct, indicating that these genes are transposons generated from Oxct. A CpG island was found within both Oxct2''s. Oxct2a and Oxct2b are located in the third introns of Bmp8a and Bmp8b, and they are positioned within a 240-kb region in a tail-to-tail orientation on chromosome 4. This structural feature was also conserved in a syntenic region of human 1p34.3. Structural similarity between mice and humans indicated that these two sets of genes were generated by a segmental gene duplication, which occurred before the primate–rodent split. Dot matrix and phylogenetic tree analyses demonstrated that multiple rounds of intrachromosomal gene conversion between the two loci occurred in each species independently. [Copyright &y& Elsevier]

A lambda clone containing a rainbow trout IL-1β1 gene was isolated by a PCR screening strategy from a genomic library cloned in lambda GEM-11, and an EcoRI fragment from this clone was fully sequenced, and contained 1680 bp 5′-flanking sequence, the whole IL-1β1 gene open reading frame, and the 3′-flanking region with two potential poly A signals and poly A sites. This clone encoded a protein that shared 99.8% identity to the previously published trout IL-1β1 cDNA sequence, with only three base substitutions. The main difference was that this clone had an additional complete HpaI SINE insertion in the 3rd intron making intron III 211 bp larger (834 bp via 623 bp). Thus this sequence was designated as allele B (Big intron III) of IL-1β1 and the previously reported sequence as allele S (Short intron III). Three lines of evidence (allele specific PCR, cloning and sequencing, and direct sequencing of PCR products) revealed that allele B was constitutively expressed and could respond to stimulation with lipopolysaccharide or trout recombinant IL-1β.Searching of the GenBank database with the HpaI SINE sequence resulted in three additional HpaI loci being identified in rainbow trout. Another SINE retroposition was also identified in the same intron of both alleles of IL-1β1 by comparison with the trout IL-1β2 gene. This novel SINE sequence, sharing high homology with the HpaI SINE at the 3′-end region, is present in EST databases of several species including human, mouse and fish. The consensus of this novel SINE shares 57 to 61% identities to tRNA–Leu from different species. Another older retroposition event in the same intron of IL-1β1 has also been hypothesised, recognised as six adenines, that may function as a RNA polIII terminator. A model for the IL-1β1 allele formation is proposed. Following the earliest retroposition into one of the two IL-1β genes that resulted from a genome duplication in salmonids, the proper environment for successive PV SINE retroposition was created. A recent retroposition of the HpaI SINE in IL-1β1 resulted in the formation of the two alleles of IL-1β1. Examination of the SINEs insertion and their host gene microenvironments revealed that the SINE retroposition does not appear random, both in the site selection and the direction of insertion. The mechanism governing this outcome is discussed. [Copyright &y& Elsevier]