RetrogeneDB–a database of plant and animal retrocopies

Rosikiewicz, Wojciech; Kabza, Michał; Kosiński, Jan G.; Ciomborowska-Basheer, Joanna; Kubiak, Magdalena Regina; Makałowska, Izabela

doi:10.1093/database/bax038

Cited by 34 publications

(51 citation statements)

References 38 publications

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“…To study the orientation-dependent transcription of the retroCNVs, we generated a strand-specific RNA-Seq dataset from 10 male individuals of the France Massif Central population (FR_C In order to accurately quantify expression levels, we focused on the recent retrocopies present in the mm10 reference genome (originated from house mouse specific retroCNV genes, and with sequence identity ≥ 95% compared with their parental genes), for which the information was directly inferred from RetrogeneDB version 2 (32). As the recently originated retrocopies are usually highly similar to their parental genes, we implemented an effective-length based approach to calculate their expression values (25).…”

Section: Transcriptional Profiling Of Retrocnvsmentioning

confidence: 99%

“…i s s t u d y , w e o n l y f o c u se d o n h o u se m o u se s p e c i f i c r e t r o C N V g e n e s , w h i c h w e re d e f i n e d a s retroposed parental genes detected in at least one house mouse individual, while absent in both the outgroup species (Mus spicilegus and Mus spretus), neither in wild individual genome sequencing data nor in the inbred reference genomes.Detection of retroCNV allelesBased on the above detected house mouse specific retroCNV genes, we performed detection of retroCNV alleles at individual genome level. For the retrocopies present in the mm10 reference genome (with sequence identity >=95% to their parental gene), we used the ones annotated in RetrogeneDB version 2(32). We searched for proper paired-end alignments (with both correct orientation and expected mapping distance) from each house mouse individual sequencing dataset, that have one read uniquely mapped to the flanking region of the annotated retrocopy and the other read mapped within the focal retrocopy region (unique mapping not required).…”

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The mutational load in natural populations is significantly affected by high primary rates of retroposition

Zhang

Xie

Ullrich

et al. 2020

Preprint

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Gene retroposition is known to contribute to patterns of gene evolution and adaptations. However, possible negative effects of gene retroposition remain largely unexplored, since most previous studies have focussed on between-species comparisons where negatively selected copies are mostly not observed, as they are quickly lost from the populations. Here, we show for natural house mouse populations that the primary rate of retroposition is orders of magnitude higher than previously thought. Comparisons with SNP distribution patterns in the same populations show that most retroposition events are deleterious. Transcriptomic profiling analysis shows that new retroposed copies become easily subject to transcription and have an influence on the expression level of their parental genes, especially when transcribed in the antisense direction. Our results imply that the impact of retroposition on the mutational load in natural populations has been highly underestimated, which has also major implications for strategies of disease allele detection in humans.

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Section: Transcriptional Profiling Of Retrocnvsmentioning

confidence: 99%

mentioning

confidence: 99%

The mutational load in natural populations is significantly affected by high primary rates of retroposition

Zhang

Xie

Ullrich

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…For the functional retrocopies analysis, the parent-retrocopy genes derived in (Parmley et al, 2007) were used. Pseudogenic retrocopies were retrieved from RetrogeneDB (Rosikiewicz et al, 2017). Retrocopy annotations were filtered to only leave human genes with a one-to-one ortholog in Macaca mulatta.…”

Section: Analysis Of Gc Content Variation In the Human Genomementioning

confidence: 99%

Codon usage and splicing jointly influence mRNA localization

Mordstein¹

2020

Preprint

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In the human genome, most genes undergo splicing and patterns of codon usage are splicing-dependent: guanine and cytosine (GC) content is highest within single-exon genes and within first exons of multi-exon genes. However, the effects of codon usage on gene expression are typically characterized in unspliced model genes. Here, we measured the effects of splicing on expression in a panel of synonymous reporter genes that varied in nucleotide composition. We found that high GC content increased protein yield, mRNA yield, cytoplasmic mRNA localization and translation of unspliced reporters. Splicing did not affect the expression of GC-rich variants. However, splicing promoted the expression of AT-rich variants by increasing their steady-state protein and mRNA levels, in part through promoting cytoplasmic localization of mRNA. We propose that splicing promotes the nuclear export of AU-rich mRNAs and that codon-and splicing-dependent effects on expression are under evolutionary pressure in the human genome.

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“…RetrogeneDB (Rosikiewicz et al, 2017). Retrocopy annotations were filtered to 846 only leave human genes with a one-to-one ortholog in Macaca mulatta.…”

Section: Analysis Of Gc Content Variation In the Human Genome 833mentioning

confidence: 99%

Splicing buffers suboptimal codon usage in human cells

Mordstein

Savisaar

Young

et al. 2019

Preprint

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1 2 Although multiple studies have addressed the effects of codon usage on gene 3 expression, such studies were typically performed in unspliced model genes. In 4 the human genome, most genes undergo splicing and patterns of codon usage are 5 splicing-dependent: guanine and cytosine (GC) content is highest within single-6 exon genes and within first exons of multi-exon genes. Intrigued by this 7 observation, we measured the effects of splicing on expression in a panel of 8 synonymous variants of GFP and mKate2 reporter genes that varied in 9 nucleotide composition. We found that splicing promotes the expression of 10 adenine and thymine (AT)-rich variants by increasing their steady-state protein 11 and mRNA levels, in part through promoting cytoplasmic localization of mRNA. 12Splicing had little or no effect on the expression of GC-rich variants. In the 13 absence of splicing, high GC content at the 5' end, but not at the 3' end of the 14 coding sequence positively correlated with expression. Among endogenous 15 human protein-coding transcripts, GC content has a more positive effect on 16 various expression measures of unspliced, relative to spliced mRNAs. We 17 propose that splicing promotes the expression of AT-rich genes, leading to 18 selective pressure for the retention of introns in the human genome. 19 20 Kudla et al., 2006;Zolotukhin et al., 1996). As a result, increasing the GC content 48 of transgenes has become a common strategy in coding sequence optimization 49 for heterologous expression in human cells (Fath et al., 2011). On the other hand, 50 genome-wide analyses of endogenous genes typically show little or no 51 correlation of GC content with expression (Duan et al., 2013;Lercher et al., 2003; 52 Rudolph et al., 2016;Semon et al., 2005). 53 4 54 We hypothesized that the conflicting results in heterologous and endogenous 55 gene expression studies can be partially explained by RNA splicing. Most 56 transgenes used in heterologous expression systems have no introns, whereas 57 97% of genes in the human genome contain one or more introns. Splicing is 58 known to influence gene expression at multiple stages, including nuclear RNP 59 assembly, RNA export, and translation. If splicing selectively increased the 60 expression of AT-rich genes, it could account for the lack of correlation of GC 61 content and gene expression in previous genome-wide studies. We therefore 62 compared spliced and unspliced genes with respect to their (1) genomic codon 63 usage, (2) expression levels of reporter genes in transient and stable transfection 64 experiments and (3) global expression patterns in human transcriptome studies. 65 We show that splicing increases the expression of AT-rich genes, but not GC-rich 66 genes, in part through effects on cytoplasmic RNA enrichment. 67 68 Results 69 70 Codon usage of human protein-coding genes depends on RNA splicing 71We first analysed the relationship between the nucleotide composition of human 72 genes and splicing. GC4 content (GC content at 4-fold degenerate site...

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RetrogeneDB–a database of plant and animal retrocopies

Cited by 34 publications

References 38 publications

The mutational load in natural populations is significantly affected by high primary rates of retroposition

The mutational load in natural populations is significantly affected by high primary rates of retroposition

Codon usage and splicing jointly influence mRNA localization

Splicing buffers suboptimal codon usage in human cells

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