Positive selection for the male functionality of a co-retroposed gene in the hominoids.
BACKGROUND
New genes generated by retroposition are widespread in humans and other mammalian species. Usually, this process copies a single parental gene and inserts it into a distant genomic location. However, retroposition of two adjacent parental genes, i.e. co-retroposition, had not been reported until the hominoid chimeric gene, PIPSL, was identified recently. It was shown how two genes linked in tandem (phosphatidylinositol-4-phosphate 5-kinase, type I, alpha, PIP5K1A and proteasome 26S subunit, non-ATPase, 4, PSMD4) could be co-retroposed from a single RNA molecule to form this novel chimeric gene. However, understanding of the origination and biological function of PIPSL requires determination of the coding potential of this gene as well as the evolutionary forces acting on its hominoid copies.


RESULTS
We tackled these problems by analyzing the evolutionary signature in both within-species variation and between species divergence in the sequence and structure of the gene. We revealed a significant evolutionary signature: the coding region has significantly lower sequence variation, especially insertions and deletions, suggesting that the human copy may encode a protein. Moreover, a survey across five different hominoid species revealed that all adaptive changes of PSMD4-derived regions occurred on branches leading to human and chimp rather than other hominoid lineages. Finally, computational analysis suggests testis-specific transcription of PIPSL is regulated by tissue-dependent methylation rather than some transcriptional leakage.


CONCLUSIONS
Therefore, this set of analyses showed that PIPSL is an extraordinary co-retroposed protein-coding gene that may participate in the male functions of humans and its close relatives.
Zhang
Yong
Y
Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, 100871, PR China. pkuzhangy@gmail.com
Lu
Shujuan
S
Zhao
Shuqi
S
Zheng
Xiaofeng
X
Long
Manyuan
M
Wei
Liping
L
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005828:Genetics, Population; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008745:Methylation; D002679:Pan troglodytes / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011323:Primates / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D016601:RNA-Binding Proteins; D018626:Retroelements; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic
D002352:Carrier Proteins; C524460:PIPSL protein, human; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; D018626:Retroelements; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D046988:Proteasome Endopeptidase Complex