Dataset Information

Evidence that alternative transcriptional initiation is largely nonadaptive.

ABSTRACT: Alternative transcriptional initiation (ATI) refers to the frequent observation that one gene has multiple transcription start sites (TSSs). Although this phenomenon is thought to be adaptive, the specific advantage is rarely known. Here, we propose that each gene has one optimal TSS and that ATI arises primarily from imprecise transcriptional initiation that could be deleterious. This error hypothesis predicts that (i) the TSS diversity of a gene reduces with its expression level; (ii) the fractional use of the major TSS increases, but that of each minor TSS decreases, with the gene expression level; and (iii) cis-elements for major TSSs are selectively constrained, while those for minor TSSs are not. By contrast, the adaptive hypothesis does not make these predictions a priori. Our analysis of human and mouse transcriptomes confirms each of the three predictions. These and other findings strongly suggest that ATI predominantly results from molecular errors, requiring a major revision of our understanding of the precision and regulation of transcription.

SUBMITTER: Xu C

PROVIDER: S-EPMC6438578 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evidence that alternative transcriptional initiation is largely nonadaptive.

Xu Chuan C Park Joong-Ki JK Zhang Jianzhi J

PLoS biology 20190318 3

Alternative transcriptional initiation (ATI) refers to the frequent observation that one gene has multiple transcription start sites (TSSs). Although this phenomenon is thought to be adaptive, the specific advantage is rarely known. Here, we propose that each gene has one optimal TSS and that ATI arises primarily from imprecise transcriptional initiation that could be deleterious. This error hypothesis predicts that (i) the TSS diversity of a gene reduces with its expression level; (ii) the frac ...[more]

PMID: 30883542

Similar Datasets

Project description:Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response.

Dataset Information

Evidence that alternative transcriptional initiation is largely nonadaptive.

Publications

Evidence that alternative transcriptional initiation is largely nonadaptive.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets