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The research team led by Professor Xiaoshu Chen and Investigator Zheng Hu have made new progress in the study of position effects

Last updated :2021-04-30

Source: Zhongshan School of Medicine
Edited by: Tan Rongyu, Wang Dongmei

Recently, the research team led by Professor Xiaoshu Chen from the Zhongshan School of Medicine of Sun Yat-sen University and the team led by Investigator Zheng Hu from the First Affiliated Hospital of Sun Yat-sen University have made new progress in the research of position effects and their externality. This new study “Transcriptome Analysis in Yeast Reveals the Externality of Position Effects” was published on April 19, 2021 in the internationally renowned journal of Molecular Biology & Evolution.

The activity of a gene newly integrated into a chromosome depends on the genomic context of the integration site. This “position effect” has been widely reported, although the other side of the coin, i.e., how the integration affects the local chromosomal environment, has remained largely unexplored. In this article, the researchers examined the transcriptome profiles of ~250 Saccharomyces cerevisiae strains, each with GFP integrated into a different locus of the wild-type strain. They found that in genomic regions enriched in essential genes, GFP expression tended to be lower, and the genes near the integration site tended to show greater expression reduction. More importantly, they found that changes in the expression of neighboring genes, but not GFP expression, are significantly associated with the cellular growth rate. As a result, genomic loci that showed high GFP expression immediately after integration were associated with growth disadvantages caused by elevated expression of neighboring genes, ultimately leading to a low total yield of GFP in the long run.

Their findings thus offer unequivocal evidence for a previously unappreciated facet of the position effects, which has profound theoretical and practical implications. First, traditional studies of the position effects focused on the influence of genomic local environment over the gene integrated into the genome, but largely ignored how the integrated gene influenced the genomic local environment. Their study therefore revealed a novel regulatory mechanism by the position effects, and contributed the largest dataset for the investigation of externality to date. Second, they found genomic evidence that the externality of position effects was at least partially explainable by the local density of essential genes, thereby offering novel mechanistic insight of the position effect and its externality. Third, by simultaneous measurement of growth rates of the ~250 constructed yeast strains, they found, unexpectedly, that cellular fitness was significantly correlated with the expression change of genes surrounding the integration site. This result highlighted the nonnegligible role of the externality in determining the phenotypic consequence of the position effects. Together, this study highlights the impact of position effects on the fate of exogenous gene integration and has significant implications for biological engineering and the pathology of viral integration into the host genome.

 
Schematic diagram of the externality of the position effect and its influence on the total yield of an integrated foreign gene.

Master student Qian Gui and doctoral student Shuyun Deng from the team of Professor Xiaoshu Chen, are the first authors of the paper. Investigator Zheng Hu and Professor Xiaoshu Chen are the co-corresponding authors of the paper. This research is supported by grants from the National Key R&D Program of China, National Special Research Program of China for Important Infectious Diseases and the National Natural Science Foundation of China.

Link to the paper: https://academic.oup.com/mbe/advance-article/doi/10.1093/molbev/msab104/6237911