Dataset Information

Tandem RNA chimeras contribute to transcriptome diversity in human population and are associated with intronic genetic variants.

ABSTRACT: Chimeric RNAs originating from two or more different genes are known to exist not only in cancer, but also in normal tissues, where they can play a role in human evolution. However, the exact mechanism of their formation is unknown. Here, we use RNA sequencing data from 462 healthy individuals representing 5 human populations to systematically identify and in depth characterize 81 RNA tandem chimeric transcripts, 13 of which are novel. We observe that 6 out of these 81 chimeras have been regarded as cancer-specific. Moreover, we show that a prevalence of long introns at the fusion breakpoint is associated with the chimeric transcripts formation. We also find that tandem RNA chimeras have lower abundances as compared to their partner genes. Finally, by combining our results with genomic data from the same individuals we uncover intronic genetic variants associated with the chimeric RNA formation. Taken together our findings provide an important insight into the chimeric transcripts formation and open new avenues of research into the role of intronic genetic variants in post-transcriptional processing events.

SUBMITTER: Greger L

PROVIDER: S-EPMC4136775 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tandem RNA chimeras contribute to transcriptome diversity in human population and are associated with intronic genetic variants.

Greger Liliana L Su Jing J Rung Johan J Ferreira Pedro G PG Lappalainen Tuuli T Dermitzakis Emmanouil T ET Brazma Alvis A

PloS one 20140818 8

Chimeric RNAs originating from two or more different genes are known to exist not only in cancer, but also in normal tissues, where they can play a role in human evolution. However, the exact mechanism of their formation is unknown. Here, we use RNA sequencing data from 462 healthy individuals representing 5 human populations to systematically identify and in depth characterize 81 RNA tandem chimeric transcripts, 13 of which are novel. We observe that 6 out of these 81 chimeras have been regarde ...[more]

PMID: 25133550

Similar Datasets

Project description:One paradigm to explain the complexity of viral RNA populations is that the low fidelity of the RNA-dependent RNA polymerase (RdRp) drives high mutation rates and consequently genetic diversity. Like most RNA viruses, wild-type yellow fever virus (YFV) replication is error-prone due to the lack of proofreading by the virus-encoded RdRp. However, there is evidence that replication of the live attenuated YF vaccine virus 17D, derived from wild-type strain Asibi, is less error-prone than wild-type RNA viruses. Recent studies comparing the genetic diversity of wild-type Asibi and 17D vaccine virus found that wild-type Asibi has the typical heterogeneous population of an RNA virus, while there is limited intra- and interpopulation variability of 17D vaccine virus. Utilizing chimeric and mutant infectious clone-derived viruses, we show that high and low genetic diversity profiles of wild-type Asibi virus and vaccine virus 17D, respectively, are multigenic. Introduction of either structural (pre-membrane and envelope) genes or NS2B or NS4B substitutions into the Asibi and 17D backbone resulted in altered variant population, nucleotide diversity, and mutation frequency compared to the parental viruses. Additionally, changes in genetic diversity of the chimeric and mutant viruses correlated with the phenotype of multiplication kinetics in human alveolar A549 cells. Overall, the paradigm that only the error-prone RdRp controls genetic diversity needs to be expanded to address the role of other genes in genetic diversity, and we hypothesize that it is the replication complex as a whole and not the RdRp alone that controls genetic diversity.IMPORTANCE With the advent of advanced sequencing technology, studies of RNA viruses have shown that genetic diversity can contribute to both attenuation and virulence and the paradigm is that this is controlled by the error-prone RNA-dependent RNA polymerase (RdRp). Since wild-type yellow fever virus (YFV) strain Asibi has genetic diversity typical of a wild-type RNA virus, while 17D virus vaccine has limited diversity, it provides a unique opportunity to investigate RNA population theory in the context of a well-characterized live attenuated vaccine. Utilizing infectious clone-derived viruses, we show that genetic diversity of RNA viruses is complex and that multiple genes, including structural genes and NS2B and NS4B genes also contribute to genetic diversity. We suggest that the replication complex as a whole, rather than only RdRp, drives genetic diversity, at least for YFV.

Project description:BACKGROUND:Life history characteristics are considered important factors influencing the evolutionary processes of natural populations, including the patterns of population genetic structure of a species. The sister species Cottus hangiongensis and C. koreanus are small bottom-dwelling freshwater sculpin fishes from South Korea that display marked life history divergence but are morphologically nearly indistinguishable. Cottus hangiongensis evolved an 'amphidromous' life history with a post-hatching pelagic larval phase. They spawn many small eggs in the low reaches of rivers, and hatched larvae migrate to the sea before returning to grow to maturity in the river mouth. In contrast, C. koreanus evolved a 'fluvial' landlocked type with benthic larvae. They release a smaller number of larger eggs, and the larvae undergo direct development, remaining benthic in the upstream rivers throughout their entire lives. We tested whether there were differences in patterns and levels of within-population genetic diversities and spatial population structure between the two closely related Korean sculpins using mitochondrial DNA control region sequences and seven nuclear microsatellite loci. RESULTS:The combined analyses of both marker sets revealed that C. hangiongensis harboured considerably higher levels of within-population genetic diversities (e.g. haplotype/allelic richness, heterozygosities) than C. koreanus. In contrast, the fluvial sculpin exhibited noticeably more spatial population structure than did the amphidromous sculpin, as suggested by pairwise FST statistics. The finding that C. hangiongensis individuals comprised a single random mating population across the east-flowing river basins in the Korean Peninsula, whereas C. koreanus individuals comprised genetically discrete individual populations, was further supported by an individual-based Bayesian population assignment and also factorial correspondence analyses. CONCLUSIONS:The higher genetic diversity, but lower population structure, of the amphidromous sculpin relative to the fluvial sculpin may have resulted from its greater larval dispersal and also possibly, higher fecundity accompanied by an amphidromous life history. Hence, we conclude that contrasting early life histories - including the presence or absence of the pelagic larval phase - may have led to divergent patterns of within-population genetic diversities and spatial population structure between the sister Cottus species following speciation from a common ancestor of marine sculpin.

Dataset Information

Tandem RNA chimeras contribute to transcriptome diversity in human population and are associated with intronic genetic variants.

Publications

Tandem RNA chimeras contribute to transcriptome diversity in human population and are associated with intronic genetic variants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets