Acquisition of inverted GSTM exons by an intron of primate GSTM5 gene

Abstract

The human GSTM gene family is composed of five gene members, GSTM1-5, and plays an important role in detoxification. In this study, the human GSTM5 gene was found to have a long inverted repeat (LIR) in intron 5. The LIR is able to form a stem-loop structure with a 31-bp stem and a 9-nt loop. The intronic LIR was also identified in other primates but not in non-primates. The human and chimpanzee LIRs had undergone compensating mutations that make the stem loop more stable, suggesting a functional role for the LIR. Sequence homology showed that the LIR was actually a part of inverted exons acquired by the intron. Results of phylogenetic analysis indicate that the inverted exons were derived from exon 5 of GSTM4 and exon 5 of GSTM1. The intronic LIR and inverted GSTM exons can probably introduce complexity in the expression of GSTM gene family.

Lirex: A Package for Identification of Long Inverted Repeats in Genomes

“…Over 100 recombinogenic LIRs were found in the human genome. Occasionally, one repeat of an LIR is located in an exon, exemplified by GSTM5 gene [10]. Involvement of an exon in the formation of a stem-loop structure would result in even more complicated gene structures by creating various alternative splicing patterns, which has not been fully acknowledged at present.…”

“…The evolutionary significance of the LIRs in primates is still under hot debate. A previous study has identified primate-specific LIRs in long introns of the genes that are involved in development of nervous systems and detoxification in humans [10]. Some of them are suggested to be inducers of cancers [11], [12].…”