Species-specific exon loss in human transcriptomes.
Changes in exon-intron structures and splicing patterns represent an important mechanism for the evolution of gene functions and species-specific regulatory networks. Although exon creation is widespread during primate and human evolution and has been studied extensively, much less is known about the scope and potential impact of human-specific exon loss events. Historically, transcriptome data and exon annotations are significantly biased toward humans over nonhuman primates. This ascertainment bias makes it challenging to discover human-specific exon loss events. We carried out a transcriptome-wide search of human-specific exon loss events, by taking advantage of RNA sequencing (RNA-seq) as a powerful and unbiased tool for exon discovery and annotation. Using RNA-seq data of humans, chimpanzees, and other primates, we reconstructed and compared transcript structures across the primate phylogeny. We discovered 33 candidate human-specific exon loss events, among which six exons passed stringent experimental filters for the complete loss of splicing activities in diverse human tissues. These events may result from human-specific deletion of genomic DNA, or small-scale sequence changes that inactivated splicing signals. The impact of human-specific exon loss events is predominantly regulatory. Three of the six events occurred in the 5' untranslated region (5'-UTR) and affected cis-regulatory elements of mRNA translation. In SLC7A6, a gene encoding an amino acid transporter, luciferase reporter assays suggested that both a human-specific exon loss event and an independent human-specific single nucleotide substitution in the 5'-UTR increased mRNA translational efficiency. Our study provides novel insights into the molecular mechanisms and evolutionary consequences of exon loss during human evolution.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles.
Jinkai
J
Wang
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles.
Zhi-xiang
ZX
Lu
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles.
Collin J
CJ
Tokheim
Department of Internal Medicine, University of Iowa.
Sara E
SE
Miller
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles yxing@ucla.edu.
Yi
Y
Xing
D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D000818:Animals; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D006801:Humans; D011323:Primates / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*
D026923:Amino Acid Transport Systems, Basic; C469951:SLC7A6 protein, human
RNA-seq; evolution; exon loss; primate; splicing