'Junk' DNA May Have Important Role In Gene Regulation

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'Junk' DNA May Have Important Role In Gene Regulation

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/10/081017080145.htm

For about 15 years, scientists have known that certain " junk " DNA --

repetitive DNA segments previously thought to have no function --

could evolve into exons, which are the building blocks for protein-

coding genes in higher organisms like animals and plants. Now, a

University of Iowa study has found evidence that a significant number

of exons created from junk DNA seem to play a role in gene regulation.

The findings, which increase understanding of how humans differ from

other animals, including non-human primates, appear Oct. 17 in the

open-access journal PLoS Genetics.

Nearly half of human DNA consists of repetitive DNA, including

transposons, which can " transpose " or move around to different

positions within the genome. A type of transposon called

retrotransposons are transcribed into RNA and then reintegrated into

the genomic DNA. The most common form of retrotransposons in the

human genome are Alu elements, which have more than one million

copies and occupy approximately 10 percent of the human genome.

" Alu elements are a major source of new exons. Because Alu is a

primate-specific retrotransposon, creation of new exons from Alu may

contribute to unique traits of primates, so we want to better

understand this process, " said the study's senior author Yi Xing,

Ph.D., assistant professor of internal medicine and biomedical

engineering, who holds a joint appointment in the University of Iowa

Carver College of Medicine and the UI College of Engineering.

To study the impact of Alu-derived exons on human gene expression,

the researchers used a high-density exon microarray. The technology

has nearly six million probes for monitoring the expression patterns

of all human exons. Using data generated by these microarrays, the

scientists analyzed 330 Alu-derived exons in 11 human tissues. The

team then identified a number of exons with interesting expression

and functional characteristics.

" Hundreds of exons in the human genome were created from Alu

elements. The whole-genome exon microarray allowed us to quickly

identify exons that most likely contribute to the regulation of gene

expression and function, " said Lan Lin, Ph.D., University of Iowa

postdoctoral fellow in internal medicine and the lead author of this

study.

Analysis of one human gene, SEPN1, which is known to be involved in a

type of muscular dystrophy, along with comparative data from

chimpanzee and macaque tissues, suggested that the presence of a

muscle-specific Alu-derived exon resulted from a human-specific

change that occurred after humans and chimpanzees diverged

evolutionarily.

" In this case, this exon is only expressed at a high level in the

human muscle but not in any other human or non-human primate tissue,

so this implies that the exon plays a functional role in muscle, and

this role is human-specific, " said Xing, who is also affiliated with

University of Iowa Center for Bioinformatics and Computational

Biology.

Other University of Iowa researchers on the paper included Shihao

Shen, master's student in biostatistics in the UI College of Public

Health; Anne Tye, undergraduate in the UI College of Liberal Arts and

Sciences and an Iowa Center for Research by Undergraduates Scholar

Assistant; Peng Jiang, Ph.D., postdoctoral fellow in internal

medicine; and Beverly son, Ph.D., UI professor of internal

medicine who holds the Roy J. Carver Biomedical Research Chair in

Internal Medicine. Cai, Ph.D., postdoctoral scholar in biology

at Stanford University, also contributed to the paper.