SIC Seminar

Host:Prof. Hyunju Lee/Language: English

Wednesday, September 25, 2013, 16:00-17:00, #115, Dasan Building

Functional genomics: the role of gene expression studies

Chungoo Park, Ph.D

School of Biological Sciences and Tehchnology, Chonnam National University
 

 
 
Abstract: In this seminar, I will present two topics.
1. High expression hampers horizontal gene transfer.
Horizontal gene transfer (HGT), the movement of genetic material from one species to another, is a common phenomenon in prokaryotic evolution. Although the rate of HGT is known to vary among genes, our understanding of the cause of this variation, currently summarized by two rules, is far from complete. The first rule states that informational genes, which are involved in DNA replication, transcription, and translation, have lower transferabilities than operational genes. The second rule asserts that prote! in interactivity negatively impacts gene transferability. Here, we hypothesize that high expression hampers HGT, because the fitness cost of an HGT to the recipient, arising from the 1) energy expenditure in transcription and translation, 2) cytotoxic protein misfolding, 3) reduction in cellular translational efficiency, 4) detrimental protein misinteraction, and 5) disturbance of the optimal protein concentration or cell physiology, increases with the expression level of the transferred gene. To test this hypothesis, we examined laboratory and natural HGTs to Escherichia coli. We observed lower transferabilities of more highly expressed genes, even after controlling the confounding factors from the two established rules and the genic GC content. Furthermore, expression level predicts gene transferability better than all other factors examined. We also confirmed the significant negative impact of gene expression on the rate of HGTs to 127 of 133 genomes of eubacteria and ar! chaebacteria. Together, these findings establish the gene expression level as a major determinant of horizontal gene transferability. They also suggest that most successful HGTs are initially slightly deleterious, fixed because of their negligibly low costs rather than high benefits to the recipient.

2. Genomic evidence for elevated mutation rates in highly expressed genes.
Reporter gene assays have demonstrated both transcription-associated mutagenesis (TAM) and transcription-coupled repair, but the net impact of transcription on mutation rate remains unclear, especially at the genomic scale. Using comparative genomics of related species as well as mutation accumulation lines, we show in yeast that the rate of point mutation in a gene increases with the expression level of the gene. Transcription induces mutagenesis on both DNA strands, indicating simultaneous actions of several TAM mechanisms. A significant positive correlation is also detected between the human germline mutation rate and expression level. These results indicate that transcription is overall mutagenic.

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Chungoo Park, Ph.D.

Assistant Professor, School of Biological Sciences and Technology,Chonnam National University
2000.2 B.S., Computer Science & Engineering, Inha University, Incheon, South Korea
2002. 2 M.S., Information and Communications, GIST,  South Korea
2010. 7 Ph.D., Biology; Molecular Evolutionary Biology option, The Pennsylvania State University, University Park, PA, USA