Biology subjects

Hunter Fraser

Publications and source records attributed to Hunter Fraser.

3 recordsLinked to original sources

bioRxiv2016

Phylogenetic expression profiling reveals widespread coordinated evolution of gene expression

Phylogenetic profiling, which infers functional relationships between genes based on patterns of gene presence/absence across species, has proven to be highly effective. Here we introduce a complementary approach, phylogenetic expression profiling (PEP), which detects gene sets with correlated expression levels across a phylogeny. Applying PEP to RNA-seq data consisting of 657 samples from 309 diverse unicellular eukaryotes, we found several hundred gene sets evolving in a coordinated fashion. These allowed us to predict a role of the Golgi apparatus in Alzheimer's disease, as well as novel genes related to diabetes pathways. We also detected adaptive evolution of tRNA ligase levels to match genome-wide codon usage. In sum, we found that PEP is an effective method for inferring functional relationships - especially among core cellular components that are never lost, to which phylogenetic profiling cannot be applied - and that many subunits of the most conserved molecular machines are coexpressed across eukaryotes.

Evolutionary Biology↗

bioRxiv2016

Cis-regulatory evolution in prokaryotes revealed by interspecific archaeal hybrids.

The study of allele-specific expression (ASE) in interspecific hybrids has played a central role in our understanding of a wide range of phenomena, including genomic imprinting, X-chromosome inactivation, and cis-regulatory evolution. However across the hundreds of studies of hybrid ASE, all have been restricted to sexually reproducing eukaryotes, leaving a major gap in our understanding of the genomic patterns of cis-regulatory evolution in prokaryotes. Here we introduce a method to generate stable hybrids between two species of halophilic archaea, and measure genome-wide ASE in these hybrids with RNA-seq. We found that over half of all genes have significant ASE, and that genes encoding kinases show evidence of lineage-specific selection on their cis-regulation. This pattern of polygenic selection suggested species-specific adaptation to low phosphate conditions, which we confirmed with growth experiments. Altogether, our work extends the study of ASE to archaea, and suggests that cis-regulation can evolve under polygenic lineage-specific selection in prokaryotes.

Evolutionary Biology↗

bioRxiv2015

Dissecting the genetic basis of a complex cis-regulatory adaptation

Although single genes underlying several evolutionary adaptations have been identified, the genetic basis of complex, polygenic adaptations has been far more challenging to pinpoint. Here we report that the budding yeast Saccharomyces paradoxus has recently evolved resistance to citrinin, a naturally occurring mycotoxin. Applying a genome-wide test for selection on cis-regulation, we identified five genes involved in the citrinin response that are constitutively up-regulated in S. paradoxus. Four of these genes are necessary for resistance, and are also sufficient to increase the resistance of a sensitive strain when over-expressed. Moreover, cis-regulatory divergence in the promoters of these genes contributes to resistance, while exacting a cost in the absence of citrinin. Our results demonstrate how the subtle effects of individual regulatory elements can be combined, via natural selection, into a complex adaptation. Our approach can be applied to dissect the genetic basis of polygenic adaptations in a wide range of species.\n\nAuthor SummaryAdaptation via natural selection has been a subject of great interest for well over a century, yet we still have little understanding of its molecular basis. What are the genetic changes that are actually being selected? While single genes underlying several adaptations have been identified, the genetic basis of complex, polygenic adaptations has been far more challenging to pinpoint. The complex trait that we study here is the resistance of Saccharomyces yeast to a mycotoxin called citrinin, which is produced by many other species of fungi, and is a common food contaminant for both humans and livestock. We found that sequence changes in the promoters of at least three genes have contributed to citrinin resistance, by up-regulating their transcription even in the absence of citrinin. Higher expression of these genes confers a fitness advantage in the presence of citrinin, while exacting a cost in its absence-- a fitness tradeoff. Our results provide a detailed view of a complex adaptation, and our approach can be applied to polygenic adaptations in a wide range of species.

Evolutionary Biology↗