Biology subjects

Yang, J.-R.

Publications and source records attributed to Yang, J.-R..

4 recordsLinked to original sources

bioRxiv2018

Specificity of RNA folding and its association with evolutionarily adaptive mRNA secondary structure

Secondary structure is a fundamental feature for both noncoding and messenger RNA. However, our understandings about the secondary structure of mRNA, especially for the coding regions, remain elusive, likely due to translation and the lack of RNA binding proteins that sustain the consensus structure, such as those bind to noncoding RNA. Indeed, mRNA has recently been found to bear pervasive alternative structures, whose overall evolutionary and functional significance remained untested. We hereby approached this problem by estimating folding specificity, the probability that a fragment of RNA folds back to the same partner once re-folded. We showed that folding specificity for mRNA is lower than noncoding RNA, and displays moderate evolutionary conservation between orthologs and between paralogs. More importantly, we found that specific rather than alternative folding is more likely evolutionarily adaptive, since it is more frequently associated with functionally important genes or sites within a gene. Additional analysis in combination with ribosome density suggests the capability of modulating ribosome movement as one potential functional advantage provided by specific folding. Our findings revealed a novel facet of RNA structome with important functional and evolutionary implications, and points to a potential way of disentangling mRNA secondary structures maintained by natural selection from molecular noise.

evolutionary biology↗

bioRxiv2018

Dosage sensitivity of X-linked genes in human embryonic single cells

Fifty years ago, Susumu Ohno proposed that the expression levels of X-linked genes have doubled as dosage compensation for autosomal genes due to degeneration of Y-linked homologs during evolution of mammalian sex chromosomes. Recent studies have nevertheless shown that the X to autosome expression ratio equals ~1 in haploid human parthenogenetic embryonic stem (pES) cells and ~0.5 in diploid pES cells, thus refuting Ohnos hypothesis. Here, by reanalyzing a RNA-seq-based single-cell transcriptome dataset of human embryos (Petropoulos, et al. 2016), we found that from the 8-cell stage until the time-point just prior to implantation, the expression levels of X-linked genes are not two-fold upregulated in male cells and gradually decrease from two-fold in female cells. This observation suggests that the expression levels of X-linked genes are imbalanced, with autosomal genes starting from the early 8-cell stage, and that the dosage conversion is fast, such that the X:AA expression ratio reaches ~0.5 in no more than a week. Additional analyses of gene expression noise further suggest that the dosage sensitivity of X-linked genes is weaker than that of autosomal genes in differentiated female cells, which contradicts a key assumption of Ohnos hypothesis. Moreover, the dosage-sensitive housekeeping genes are preferentially located on autosomes, implying selection against X-linkage for dosage-sensitive genes. Our results collectively suggest an alternative to Ohnos hypothesis that X-linked genes are less likely to be dosage sensitive than autosomal genes.

genomics↗

bioRxiv2016

Intra- and inter-specific variations of gene expression levels in yeast are largely neutral

It is commonly, although not universally, accepted that most intra- and inter-specific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only [~]0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra- and inter-specific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution.

evolutionary biology↗

bioRxiv2016

Deciphering the genic basis of environmental adaptations by simultaneous forward and reverse genetics in Saccharomyces cerevisiae

The budding yeast Saccharomyces cerevisiae is the best studied eukaryote in molecular and cell biology, but its utility for understanding the genetic basis of natural phenotypic variation is limited by the inefficiency of association mapping owing to strong and complex population structure. To facilitate association mapping, we analyzed 190 high-quality genomes of diverse strains, including 85 newly sequenced ones, to uncover yeasts population structure that varies substantially among genomic regions. We identified 181 yeast genes that are absent from the reference genome and demonstrated their expression and role in important functions such as drug resistance. We then simultaneously measured the growth rates of over 4500 lab strains each deficient of a nonessential gene and 81 natural strains across multiple environments using unique DNA barcode present in each strain. We combined the genome-wide reverse genetic information with genome-wide association analysis to determine potential genomic regions of importance to environmental adaptations, and for a subset experimentally validated their role by reciprocal hemizygosity tests. The resources provided permit efficient and reliable association mapping in yeast and significantly enhances its value as a model for understanding the genetic mechanisms of phenotypic polymorphism and evolution.

genomics↗