[Frontiers in Bioscience E2, 1334-1343, June 1, 2010]

Evolution of peroxisome proliferator-activated receptor gamma alternative splicing

Tonghai Dou1,2, Jiaxi Xu3, Yuan Gao1, Jianlei Gu1, Chaoneng Ji3, Yi Xie3, Yan Zhou1,4

1 Department of Microbiology, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China, 2 Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China, 3State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China, 4Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, People's Republic of China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Material and methods
3.1. Sequence collection
3.2. Isoform identification
3.3. Ka/Ks
3.4. SNP
4. Results
4.1. Genomic Comparison
4.2. Exon Profile
4.3. SNP frequency
4.4. Ka/Ks in coding alternative splicing exon (exon B)
5. Discussion
5.1. Evolutionary history of the alternative splicing exons
5.2. Implication of high SNP frequency
5.3. The Ka/Ks story
6. Conclusion
7. Acknowledgments
8. Reference

1. ABSTRACT

Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays an important role in the control of energy balance and lipid and glucose homeostasis. Different transcript variants were investigated not only in human but also in other vertebrates. To look into the evolutionary changes of these variants, we analyzed the genomic sequences of PPAR gamma genes from several vertebrate species, as well as their mRNA and EST data. Several potential alternative splicing exons at the 5'-end of the PPAR gamma gene were identified. The 5'-end of the PPAR gamma gene is discovered to be evolutionarily active and recruits new exons via different strategies. Moreover, it is shown that the only coding alternative exon (exon B) processes much higher Ka/Ks compared with its constitutive counterparts. In addition, its Ka/Ks is greater than 1 in the rat, mouse, and rabbit, indicating adaptive evolution and possible energy storage related gain-of-function for the exon.