Alu-derived old world monkeys exonization event and experimental validation of the LEPR gene.
The leptin receptor (LEPR) is a crucial regulatory protein that interacts with Leptin. In our analysis of LEPR, novel AluJb-derived alternative transcripts were identified in the genome of the rhesus monkey. In order to investigate the occurrence of AluJb-derived alternative transcripts and the mechanism underlying exonization events, we conducted analyses using a number of primate genomic DNAs and adipose RNAs of tissue and primary cells derived from the crab-eating monkey. Our results demonstrate that the AluJb element has been integrated into our common ancestor genome prior to the divergence of simians and prosimians. The lineage-specific exonization event of the LEPR gene in chimpanzees, orangutans, and Old World monkeys appear to have been accomplished via transition mutations of the 5' splicing site (second position of C to T). However, in New World monkeys and prosimians, the AluJb-related LEPR transcript should be silenced by the additional transversion mutation (fourth position of T to G). The AluJb-related transcript of human LEPR should also be silenced by a mutation of the 5' splicing site (first position of G to A) and the insertion of one nucleotide sequence (minus fourth position of A). Our data suggests that lineage-specific exonization events should be determined by the combination event of the formation of splicing sites and protection against site-specific mutation pressures. These evolutionary mechanisms could be major sources for primate diversification.
Huh
Jae-Won
JW
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, 363-883, Korea.
Kim
Young-Hyun
YH
Kim
Dae-Soo
DS
Park
Sang-Je
SJ
Lee
Sang-Rae
SR
Kim
Sang-Hyun
SH
Kim
Ekyune
E
Kim
Sun-Uk
SU
Kim
Myeong-Su
MS
Kim
Heui-Soo
HS
Chang
Kyu-Tae
KT
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics; D020087:Alu Elements / Q000235:genetics; D000818:Animals; D005075:Biological Evolution; D002460:Cell Line; D002520:Cercopithecidae; D004252:DNA Mutational Analysis; D020868:Gene Silencing; D016678:Genome; D006801:Humans; D009154:Mutation / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*
D022821:RNA Splice Sites; D054411:Receptors, Leptin