LIPH gene (Lipase member H) located on human 3q27 is reported to be related to hair growth and loss by deletion mechanism of fourth exon. The deletion mechanism is occurred by the homologous recombination and excision event of similar Alu elements of AluSc and AluY. In this report, we investigated the evolutionary mechanism and conservation of exon 4 sequences of LIPH gene. PCR amplification indicated that AluY element have been integrated into our common ancestor genome after the divergence of Old World monkeys and Hominoid primate. Sequencing analysis of various primates DNA samples (5 hominoids, 6 Old World monkeys, and 4 New World monkeys) of exon 4 region shows one non-synonymous substitution, indicating that the region is important portion for the functional protein. The substitution event from Iso to Thr has been occurred in hominoid lineage.………………………………….…………

Evolutionary relationship of LIPH gene and Alu elementJin-Han Bae1, Sang-Je Park1, Jae-Won Huh1, Dae-Soo Kim2, and Heui-Soo Kim1, 2

1 Division of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea

2 PBBRC, Interdisciplinary Research Program of Bioinformatics, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea

http:// www.primate.or.kr

Abstract

RNA intermediate

- LTR element + LTR element

- env + env

- RT + RT

Yeast Ty1/copia/truncated HERVs

LTR ORF1 ORF2 LTR

LTR LTR

Human THE1

ORF1 ORF2PPoly(A)

L1

gag pol envLTR LTR

Full-length HERVs/exogenous retrovirus

Retroelement

Retroposon

Retrotrnasposon

Retrovirus

LINE

PPoly(A)

Human Alu

SINE

Other region

16%

LINE

20%

Coding sequence

3%

Pseudogene1%

HERV element8%

DNA element3%

Gene-related Sequence

36%

SINE13%

Introduction

Materials & Methods

Results & Discussion

7SL-derived leftmonomer

A-richconnector

7SL-derived rightmonomer poly(A)

TSDTSD

B boxA box

X 35

Denature

Anneal

Extension

Template DNA

94℃

Primer

DNA polymerase

50℃

72℃

PCRGene Cloning

& Sequencing

Bioinformatics

References

HUM CH GO GI JM RM

641 b p

L I P H (lipase, member H)

3q27MIR CDS AluY UTR

Chr.3

…

Exon

1 2 3 4 5 6 7 8 9 10S

AS

AluS

c

Insertion of AluY

Sequence analysis of Exon4 in LIPH

Amino acids of Exon4 in LIPH

HU

GO

BO

GI

OR

CR

CA

JM

SQ

RH

TA

NM

MAN

LAN

COL

0.0000.0050.0100.0150.0200.025

I

II

Phylogenic analysis of Exon4 in LIPH

Sequence analysis of Exon4 in various species

1. Kazantseva A, Goltsov A, Zinchenko R, Grigorenko AP, Abrukova AV, Moliaka YK, Kirillov AG, Guo Z, Lyle S, Ginter EK, Rogaev EI. Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH. Science. 2006 Nov 10;314(5801):982-5.

2. Ali G, Chishti MS, Raza SI, John P, Ahmad W. A mutation in the lipase H (LIPH) gene underlie autosomal recessive hypotrichosis. Hum Genet. 2007 May;121(3-4):319-25. Epub 2007 Feb 27.

3. Mills RE, Bennett EA, Iskow RC, Devine SE. Which transposable elements are active in the human genome? Trends Genet. 2007 Apr;23(4):183-91. Epub 2007 Feb 27. Review.

HuHu

FrogFrog

ChCh

CanisCanis

MusMus

GallusGallus

RabbitRabbit

FrogFrog

HuHu

ChCh

CanisCanis

MusMus

GallusGallus

RabbitRabbit

FrogFrog

HuHu

ChCh

CanisCanis

MusMus

GallusGallus

RabbitRabbit

FrogFrog

HuHu

ChCh

CanisCanis

MusMus

GallusGallus

RabbitRabbit

FrogFrog

HuHu

ChCh

CanisCanis

MusMus

GallusGallus

RabbitRabbit

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Sequence analysis of AluY