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Open Access Open Badges Research article

Human-specific protein isoforms produced by novel splice sites in the human genome after the human-chimpanzee divergence

Dong Seon Kim and Yoonsoo Hahn*

Author affiliations

Department of Life Science, Research Center for Biomolecules and Biosystems, Chung-Ang University, Seoul 156-756, Korea

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Citation and License

BMC Bioinformatics 2012, 13:299  doi:10.1186/1471-2105-13-299

Published: 13 November 2012



Evolution of splice sites is a well-known phenomenon that results in transcript diversity during human evolution. Many novel splice sites are derived from repetitive elements and may not contribute to protein products. Here, we analyzed annotated human protein-coding exons and identified human-specific splice sites that arose after the human-chimpanzee divergence.


We analyzed multiple alignments of the annotated human protein-coding exons and their respective orthologous mammalian genome sequences to identify 85 novel splice sites (50 splice acceptors and 35 donors) in the human genome. The novel protein-coding exons, which are expressed either constitutively or alternatively, produce novel protein isoforms by insertion, deletion, or frameshift. We found three cases in which the human-specific isoform conferred novel molecular function in the human cells: the human-specific IMUP protein isoform induces apoptosis of the trophoblast and is implicated in pre-eclampsia; the intronization of a part of SMOX gene exon produces inactive spermine oxidase; the human-specific NUB1 isoform shows reduced interaction with ubiquitin-like proteins, possibly affecting ubiquitin pathways.


Although the generation of novel protein isoforms does not equate to adaptive evolution, we propose that these cases are useful candidates for a molecular functional study to identify proteomic changes that might bring about novel phenotypes during human evolution.

Splice site; Human genome; Protein variant; Molecular evolution