The PLOS Genetics Editors-in-Chief and Senior Editors congratulate Santiago Naranjo, Justin D. Smith, Carlo G. Artieri, Mian Zhang, Yiqi Zhou, Michael E. Palmer and Hunter B. Fraser, authors of the article chosen as the recipient of the PLOS Genetics Research Prize 2016, Dissecting the Genetic Basis of a Complex cis-Regulatory Adaptation.
In the winning article, Naranjo and colleagues set out to identify the molecular basis of polygenic adaptation. To achieve this goal, they used a clever approach in testing for evidence of selection on gene expression (via a sign-test), specifically looking for sets of genes showing allele-specific expression in F1 hybrids between Saccharomyces paradoxus and S. cerevisiae. The authors found that genes from a pathway involved in resistance to citrinin – a naturally occurring mycotoxin produced by fungi – showed highly significant bias towards the S. paradoxus alleles. Growth assays with several strains showed that S. paradoxus recently evolved citrinin resistance. RNA-sequence analysis on hybrids exposed to citrinin was used to identify candidate genes underlying this resistance. The authors identified five candidates and were able to confirm four of them by knockout. Promoter-replacement experiments showed that S. paradoxus promoters drive much of the identified divergence in expression. Higher expression of these genes confers a fitness advantage in the presence of citrinin, while exacting a cost in its absence—a fitness trade-off.
Overall, the manuscript makes a major contribution to our understanding of evolutionary processes, telling a comprehensive story. It uses an elegant approach to screen for cis-regulatory divergence of expression and then follows up candidate genes with functional tests to better understand their underlying molecular mechanisms. The editors were particularly impressed not only with this specific result – demonstrating how small individual effects of regulatory elements can together have a large impact on fitness – but also the potential of the overall approach to be used to identify the genetic basis of polygenic adaptation in additional conditions or species.
The PLOS Genetics Research Prize was born from the editors’ desire to recognize the outstanding work published in the journal, and was launched in 2015 as part of the journal’s 10-year anniversary celebrations. This year members of the genetics community nominated their favorite research article published in PLOS Genetics in 2015, with Senior Editors selecting the winning article from these nominations based on scientific excellence and the community impact of the work. Last year’s winning article described adaptation dynamics of Escherichia coli populations evolving in the complex environment of the mammalian intestine.