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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.

New genes are of recent origin and only present in a subset of species in a phylogeny. Accumulated evidence suggests that new genes, like old genes that are conserved across species, can also take on important functions and be essential for the survival and reproductive success of organisms. Although there are detailed analyses of the mechanisms underlying new genes’ gaining fertility functions, how new genes rapidly become essential for viability remains unclear. We focused on a young retro-duplicated gene (CG7804, which we named Cocoon) in Drosophila that originated between 4 and 10 Ma. We found that, unlike its evolutionarily conserved parental gene, Cocoon has evolved under positive selection and accumulated many amino acid differences at functional sites from the parental gene. Despite its young age, Cocoon is essential for the survival of Drosophila melanogaster at multiple developmental stages, including the critical embryonic stage, and its expression is essential in different tissues from those of its parental gene. Functional genomic analyses found that Cocoon acquired unique DNA-binding sites and has a contrasting effect on gene expression to that of its parental gene. Importantly, Cocoon binding predominantly locates at genes that have other essential functions and/or have multiple gene–gene interactions, suggesting that Cocoon acquired novel essential function to survival through forming interactions that have large impacts on the gene interaction network. Our study is an important step toward deciphering the evolutionary trajectory by which new genes functionally diverge from parental genes and become essential.

Rabbitfish (Siganidae) are coral reef fish that are distributed across diverse habitats that include estuaries, mangroves, reefs, and even seaweed mats. Given their ecological diversity and natural widespread distributions across the Indo-Pacific region, we were interested to investigate the evolutionary history of this group and patterns of divergence that have contributed to their present-day distributions. In the present study, samples were collected from the South China Sea to study taxonomic and phylogenetic relationships, and divergence times. We investigated the taxonomic relationships among modern rabbitfish species, reconstructed their molecular phylogeny, and estimated divergence times among selected lineages based on a fragment of the mtDNA cytochrome oxidase I (COI) and sequences of the nuclear rhodopsin retrogene (RHO). Our results indicate that modern rabbitfish likely originated in the Indo-West Pacific during the late Eocene [37.4 million years ago (mya)], following which they diverged into three major clades during the Pliocene/Pleistocene. Subsequent diversification and origins of the majority of siganids may likely be associated with episodes of paleo-oceanographic events, including greenhouse and glaciation events (Eocene–Miocene) as well as major plate tectonic events (Pliocene–Pleistocene). Some modern siganid species may naturally hybridize with congeneric species where their geographical ranges overlap. A comprehensive taxonomic analysis revealed that the phylogeny of Siganidae (cladogenesis of Clades I, II, and III) is characterized by divergence in several external morphological characters and morphometric parameters. Our study demonstrates that morphological characteristics, geographical heterogeneity, and environmental change have contributed to siganids’ historical diversification.

Evolving to become bigger and/or longer lived should increase cancer susceptibility, but this predicted increase is not observed, a contradiction named Peto's paradox. A solution is that cancer suppression evolves to minimize cancer susceptibility, and the discovery of 19 retrogene (RTG) copies of the tumor suppressor gene TP53 in the African elephant (Loxodonta africana) is increasingly cited as a classic example of such adaptive suppression. However, classic examples need rigorous evaluation and an alternative hypothesis is that the RTGs spread by genetic drift. This study shows that before its duplication, the ancestral elephant RTG was already truncated from 390 amino acids to 157 by a frameshift mutation, and that 14 of the 19 copies are now truncated to ≤88 amino acids. There was no compelling evidence of either positive or negative selection acting on these 88 codons, and the pattern of RTG accumulation fits a neutral model with a duplication rate of ~10−6 per generation. It is concluded that there is no evidence supporting the hypothesis that the 19 elephant RTGs spread to fixation by selection; instead, the evidence indicates that these RTGs accumulated primarily by segmental duplication and drift. It is shown that the evolutionary multistage model of carcinogenesis (EMMC) predicts the recruitment of 1–2 independently acting tumor suppressor genes to suppress the increased cancer risk in elephants, so it is possible that one or a few RTGs may have been favored by selection resulting in the known enhanced sensitivity of elephant cells to DNA damage. However, the analysis does not provide any support for either a direct (via conserved TP53 activity) or indirect (via supporting canonical TP53 function) role of the RTGs sequences, so that the presence of multiple copies of TP53 retrogenes in elephants needs to be further justified before being used as a classic example of tumor suppression in large‐bodied animals.

KLHL and the related KBTBD genes encode components of the Cullin-E3 ubiquitin ligase complex and typically target tissue-specific proteins for degradation, thereby affecting differentiation, homeostasis, metabolism, cell signaling, and the oxidative stress response. Despite their importance in cell function and disease (especially, KLHL40, KLHL41, KBTBD13, KEAP1, and ENC1), previous studies of epigenetic factors that affect transcription were predominantly limited to promoter DNA methylation. Using diverse tissue and cell culture whole-genome profiles, we examined 17 KLHL or KBTBD genes preferentially expressed in skeletal muscle or brain to identify tissue-specific enhancer and promoter chromatin, open chromatin (DNaseI hypersensitivity), and DNA hypomethylation. Sixteen of the 17 genes displayed muscle- or brain-specific enhancer chromatin in their gene bodies, and most exhibited specific intergenic enhancer chromatin as well. Seven genes were embedded in super-enhancers (particularly strong, tissue-specific clusters of enhancers). The enhancer chromatin regions typically displayed foci of DNA hypomethylation at peaks of open chromatin. In addition, we found evidence for an intragenic enhancer in one gene upregulating expression of its neighboring gene, specifically for KLHL40/HHATL and KLHL38/FBXO32 gene pairs. Many KLHL/KBTBD genes had tissue-specific promoter chromatin at their 5′ ends, but surprisingly, two (KBTBD11 and KLHL31) had constitutively unmethylated promoter chromatin in their 3′ exons that overlaps a retrotransposed KLHL gene. Our findings demonstrate the importance of expanding epigenetic analyses beyond the 5′ ends of genes in studies of normal and abnormal gene regulation.

Background The cytosolic arrestin proteins mediate desensitization of activated G protein-coupled receptors (GPCRs) via competition with G proteins for the active phosphorylated receptors. Arrestins in active, including receptor-bound, conformation are also transducers of signaling. Therefore, this protein family is an attractive therapeutic target. The signaling outcome is believed to be a result of structural and sequence-dependent interactions of arrestins with GPCRs and other protein partners. Here we elucidated the detailed evolution of arrestins in deuterostomes. Results Identity and number of arrestin paralogs were determined searching deuterostome genomes and gene expression data. In contrast to standard gene prediction methods, our strategy first detects exons situated on different scaffolds and then solves the problem of assigning them to the correct gene. This increases both the completeness and the accuracy of the annotation in comparison to conventional database search strategies applied by the community. The employed strategy enabled us to map in detail the duplication- and deletion history of arrestin paralogs including tandem duplications, pseudogenizations and the formation of retrogenes. The two rounds of whole genome duplications in the vertebrate stem lineage gave rise to four arrestin paralogs. Surprisingly, visual arrestin ARR3 was lost in the mammalian clades Afrotheria and Xenarthra. Duplications in specific clades, on the other hand, must have given rise to new paralogs that show signatures of diversification in functional elements important for receptor binding and phosphate sensing. Conclusion The current study traces the functional evolution of deuterostome arrestins in unprecedented detail. Based on a precise re-annotation of the exon-intron structure at nucleotide resolution, we infer the gain and loss of paralogs and patterns of conservation, co-variation and selection.

Transposable elements, often considered to be not important for survival, significantly contribute to the evolution of transcriptomes, promoters, and proteomes. Reverse transcriptase, encoded by some transposable elements, can be used in trans to produce a DNA copy of any RNA molecule in the cell. The retrotransposition of protein-coding genes requires the presence of reverse transcriptase, which could be delivered by either non-long terminal repeat (non-LTR) or LTR transposons. The majority of these copies are in a state of “relaxed” selection and remain “dormant” because they are lacking regulatory regions; however, many become functional. In the course of evolution, they may undergo subfunctionalization, neofunctionalization, or replace their progenitors. Functional retrocopies (retrogenes) can encode proteins, novel or similar to those encoded by their progenitors, can be used as alternative exons or create chimeric transcripts, and can also be involved in transcriptional interference and participate in the epigenetic regulation of parental gene expression. They can also act in trans as natural antisense transcripts, microRNA (miRNA) sponges, or a source of various small RNAs. Moreover, many retrocopies of protein-coding genes are linked to human diseases, especially various types of cancer.

Background Processed pseudogenes and retrogenes are defined by their RNA-mediated origin and, by virtue of this origin-based definition, are often interpreted as discrete genomic insertions. The completion of telomere-to-telomere (T2T) reference assemblies has substantially improved the resolution of segmental duplication architectures and centromeric satellite sequences that were previously inaccessible, allowing genomic structural contexts that were effectively invisible in earlier references to be directly examined. Results Using the SEPTIN14P-CICP locus family as a case study, chain-based comparative analyses showed that a genomic window spanning the SEPTIN14 3′ terminal exon and the adjacent processed pseudogene CICP12 is dispersed into multiple segmental duplication-associated units across great apes, rather than being maintained as a single orthologous locus. Genome-wide analyses further indicated that annotated CICP loci preferentially localize within segmental duplication blocks and accumulate near pericentromeric or subtelomeric regions. Despite this duplication-associated dispersion, codon-based selection analyses revealed pervasive purifying selection acting on the full-length SEPTIN14 coding sequence and its 3′ terminal exon, arguing against a model in which the terminal exon was newly formed through segmental duplication. Together, these results show that when highly conserved, strongly constrained coding regions are embedded within segmental duplication-rich regions, co-dispersed processed pseudogene copies can be interpreted as distinct from independently generated LINE-1-mediated insertions and as reflecting secondary structural propagation. Conclusions When considered in light of origin-based definitions of processed pseudogenes and retrogenes, and specifically within duplication-rich and structurally unstable genomic regions resolved by T2T-level assemblies, these results suggest that multiple annotated loci can arise through secondary propagation of a single RNA-derived insertion. Under such contexts, incorporation of selective constraint and cross-species conservation enables more reliable distinction between source insertions and their secondarily propagated copies. This case study highlights a limitation of current annotation frameworks and demonstrates the need for more precise annotation that incorporates evolutionary and structural context in the T2T era.

Pigment production and distribution is controlled through multiple genes, resulting in a wide range of coat color phenotypes in dogs. Dogs that produce only the pheomelanin pigment vary in intensity from white to deep red. The Poodle breed has a wide range of officially recognized coat colors, including the pheomelanin-based white, cream, apricot, and red coat colors, which are not fully explained by the previously identified genetic variants involved in pigment intensity. Here, a genome-wide association study for pheomelanin intensity was performed in Poodles which identified an association on canine chromosome 18. Whole-genome sequencing data revealed an SNN retrocopy insertion (SNNL1) in apricot and red Poodles within the associated region on chromosome 18. While equal numbers of melanocytes were observed in all Poodle skin hair bulbs, higher melanin content was observed in the darker Poodles. Several genes involved in melanogenesis were also identified as highly overexpressed in red Poodle skin. The most differentially expressed gene however was GPR22, which was highly expressed in red Poodle skin while unexpressed in white Poodle skin (log2 fold change in expression 6.1, P < 0.001). GPR22 is an orphan G-protein-coupled receptor normally expressed exclusively in the brain and heart. The SNNL1 retrocopy inserted 2.8 kb upstream of GPR22 and is likely disrupting regulation of the gene, resulting in atypical expression in the skin. Thus, we identify the SNNL1 insertion as a candidate variant for the CFA18 pheomelanin intensity locus in red Poodles.

Premature degeneration of the intervertebral disc and its association with specific chondrodystrophic dog breeds has been recognized for over a century. Several lines of evidence including disease breed predisposition, studies suggesting heritability of premature intervertebral disc degeneration (IVDD) and association of a dog chromosome 12 (CFA 12) locus with intervertebral disc calcification have strongly supported a genetic component in IVDD in dogs. Recent studies documenting association of IVDD with an overexpressing FGF4 retrogene on CFA 12 have opened up new areas of investigation to further define the pathophysiology of premature IVDD. While preliminary data from studies investigating FGF4 retrogenes in IVDD implicate FGF4 overexpression as a major disease factor, they have also highlighted knowledge gaps in our understanding of intervertebral disc herniation which is a complex and multifactorial disease process.