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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
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Species-specific exon loss in human transcriptomes.

Jinkai Wang1, Zhi-xiang Lu1, Collin J Tokheim1

  • 1Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles.

Molecular Biology and Evolution
|November 16, 2014
PubMed
Summary

Human-specific exon loss events, while understudied, significantly impact gene regulation. This research identified 33 candidate events, with six confirmed losses affecting mRNA translation and gene function during human evolution.

Keywords:
RNA-seqevolutionexon lossprimatesplicing

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Area of Science:

  • Evolutionary biology
  • Genomics
  • Molecular biology

Background:

  • Exon-intron structure changes drive gene function evolution.
  • Exon creation is well-studied in human evolution, but exon loss is less understood.
  • Transcriptome data bias towards humans hinders discovery of human-specific exon loss.

Purpose of the Study:

  • To conduct a transcriptome-wide search for human-specific exon loss events.
  • To investigate the evolutionary impact of these events on gene regulation and function.

Main Methods:

  • Utilized RNA sequencing (RNA-seq) data from humans and other primates.
  • Reconstructed and compared transcript structures across primate phylogeny.
  • Applied stringent experimental filters to validate exon loss and splicing inactivation.

Main Results:

  • Discovered 33 candidate human-specific exon loss events.
  • Confirmed six events with complete loss of splicing activity in human tissues.
  • Identified regulatory impacts, including effects on mRNA translation efficiency in the 5'-UTR of SLC7A6.

Conclusions:

  • Human-specific exon loss is a significant evolutionary mechanism.
  • These events primarily exert regulatory effects, influencing mRNA translation.
  • The study offers new insights into molecular mechanisms and evolutionary consequences of exon loss in human evolution.