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Báo cáo khoa học: Genome-wide identification of glucosinolate synthesis genes in Brassica rapa potx

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genes in Brassica rapaYun-Xiang Zang1,2,*, Hyun Uk Kim1,*, Jin A Kim1, Myung-Ho Lim1, Mina Jin1, Sang Choon Lee1, Soo-Jin Kwon1, Soo-In Lee1, Joon Ki Hong1, Tae-Ho Park1, Jeong-Hwan Mun1

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genes in Brassica rapa

Yun-Xiang Zang1,2,*, Hyun Uk Kim1,*, Jin A Kim1, Myung-Ho Lim1, Mina Jin1, Sang Choon Lee1, Soo-Jin Kwon1, Soo-In Lee1, Joon Ki Hong1, Tae-Ho Park1, Jeong-Hwan Mun1, Young-Joo Seol1, Seung-Beom Hong3and Beom-Seok Park1

1 Genomics Division, Department of Agricultural Bio-resources, National Academy of Agricultural Science (NAAS), Rural Development Administration (RDA), Suwon, Korea

2 School of Agricultural and Food Science, Zhejiang Forestry University, Lin’an, Hangzhou, China

3 Department of Biology, San Jacinto College, Houston, TX, USA

Keywords

bioinformatics; biosynthesis pathway;

Brassica rapa; gene identification;

glucosinolate

Correspondence

B S Park, Genomics Division, Department

of Agricultural Bio-resources, National

Academy of Agricultural Science (NAAS),

Rural Development Administration (RDA),

Suwon 441-707, Korea

Fax: +82 31 299 1672

Tel: +82 31 299 1671

E-mail: pbeom@rda.go.kr

*These authors contributed equally to this work

Database

The following have been deposited to the

GenBank database Accession numbers are

shown in parenthesis: BrBCAT4 (FJ376036–

FJ376037), BrMAM (FJ376038–FJ376041),

BrBCAT3 (FJ376042–FJ376043), BrCYP79F1

(FJ376044), BrCYP79B2 (FJ376045–

FJ376046), BrCYP79B3 (FJ376047),

BrCYP79A2-1 (FJ376048), BrCYP83A1

(FJ376049–FJ376050), BrCYP83B1

(FJ376051), BrC-S lyase (FJ376052–

FJ376053), BrUGT74B1-1 (FJ376054),

BrUGT74C1 (FJ376055–FJ376057), BrST5a

(FJ376058–FJ376059), BrST5b (FJ376060–

FJ376068), BrST5c-1 (FJ376069), BrFMOGS-OX1

(FJ376070), BrFMOGS-OX5(FJ376071),

BrAOP2 (FJ376073), BrGSL-OH (FJ376074),

BrBZO1p (FJ376075), BrDof1.1 (FJ584284–

FJ584285), BrIQD1-1 (FJ584286), BrMYB28

(FJ584287–FJ584289), BrMYB29 (FJ584290–

FJ584292), BrMYB34 (FJ584293–FJ584295),

BrMYB51 (FJ584296–FJ584299),

BrMYB122-1 (FJ584300)

(Received 15 February 2009, revised 31

March 2009, accepted 24 April 2009)

doi:10.1111/j.1742-4658.2009.07076.x

Glucosinolates play important roles in plant defense against herbivores and microbes, as well as in human nutrition Some glucosinolate-derived isothi-ocyanate and nitrile compounds have been clinically proven for their anti-carcinogenic activity To better understand glucosinolate biosynthesis in Brassica rapa, we conducted a comparative genomics study with Arabidopsis thaliana and identified total 56 putative biosynthetic and regulator genes This established a high colinearity in the glucosinolate biosynthesis path-way between Arabidopsis and B rapa Glucosinolate genes in B rapa share 72–94% nucleotide sequence identity with the Arabidopsis orthologs and exist in different copy numbers The exon⁄ intron split pattern of B rapa is almost identical to that of Arabidopsis, although inversion, insertion, dele-tion and intron size variadele-tions commonly occur Four genes appear to be nonfunctional as a result of the presence of a frame shift mutation and retrotransposon insertion At least 12 paralogs of desulfoglucosinolate sulfotransferase were found in B rapa, whereas only three were found in Arabidopsis The expression of those paralogs was not tissue-specific but varied greatly depending on B rapa tissue types Expression was also developmentally regulated in some paralogs but not in other paralogs Most of the regulator genes are present as triple copies Accordingly, gluc-osinolate synthesis and regulation in B rapa appears to be more complex than that of Arabidopsis With the isolation and further characterization of the endogenous genes, health-beneficial vegetables or desirable animal feed crops could be developed by metabolically engineering the glucosinolate pathway

Abbreviations

BAC, bacterial artificial chromosome; CDS, coding sequence; EST, expressed sequence tag; LTR, long terminal repeat; MAM,

methylthioalkylmalate synthase; NCBI, National Center for Biotechnology Information.

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Glucosinolates, a group of sulfur-rich secondary

metabolites, have received much attention because

their breakdown products display several potent

bio-activities that serve as plant defense, as well as

anti-carcinogenesis compounds, in mammals [1–3] Upon

tissue disruption, the enzyme myrosinase cleaves off

the glucose group from a glucosinolate, and the

remaining molecule then quickly converts to a

bioac-tive substance (i.e an isothiocyanate, nitrile or

thiocya-nate) Among the isothiocyanates, sulforaphane, a

derivative of glucoraphanin, is known to be the most

promising anticancer agent because of its strong and

broad spectrum activity against several types of cancer

cells [3–10] Indole-3-carbinol, a derivative of

gluco-brassicin, also comprises a good anticarcinogen Both

exhibit their effects by inducing phase II detoxification

enzymes, altering estrogen metabolism, blocking the

cell cycle or protecting against oxidative damages

[11–15] Phenethyl isothiocyanate, a derivative of

gluconasturtiin, was reported to be effective for

chemoprotection [16–18], although it possesses

geno-toxic activity [19–21] Crambene

(1-cyano-2-hydroxy-3-butene), an aliphatic nitrile derived from progoitrin,

upregulates the synthesis of glutathione S-transferase

in the liver and other organs [22]

Glucosinolates are classified into three major groups,

namely aliphatic, indolyl and aromatic glucosinolates,

based on the amino acids from which they are

synthe-sized [23] Biosynthesis of aliphatic and aromatic

gluc-osinolates generally involves three steps (Fig 1) and

begins with the elongation of methionine and

phenyl-alanine, respectively The initial step of aliphatic

glucosinolate synthesis is catalyzed by

methylthioalkyl-malate synthase (MAM) to form the elongated

homologs [24,25] The core structures are made via

oxidation by cytochrome P450 enzymes, CYP79 and

CYP83, followed by C-S cleavage, glucosylation and

sulfation Finally, the side chains are modified by

oxidation, elimination, akylation or esterification

Some of the genes involved in this step, FMOGS-OX15,

AOP, GSL-OH and BZO1, have been isolated recently

[26–31]

Cruciferous vegetables, including broccoli, cabbage,

Chinese cabbage, cauliflower, and brussels sprouts, are

rich in glucosinolates A high intake of cruciferous

vegetables was shown to significantly reduce the risk

of certain cancers and cardiovascular diseases [32–34]

Chinese cabbage (Brassica rapa ssp pekinensis) is one

of the most highly consumed vegetable crops in Asia

However, unlike broccoli, many Chinese cabbage

culti-vars do not produce detectable levels of glucoraphanin

To date, most of the structural genes responsible for

the biosynthesis of the three groups of glucosinolates

have been identified and characterized in Arabidopsis [23,35] In addition, several regulators that control glucosinolate biosynthesis have been identified recently

in Arabidopsis [36–43] However, little is known about the specific genes existing in Brassica crops, except for the MAM and AOP genes in Brassica oleracea [44–46] The glucosinolate profile is highly dependent on genotype, although it is also affected by developmental

or environmental changes [47–49] Previously, we reported that the ectopic expression of Arabidopsis glucosinolate synthesis genes altered the glucosinolate profile in Chinese cabbage [50,51] Because most of the Arabidopsis genes encoding glucosinolate biosynthesis pathways have been identified and Chinese cabbage is

a close relative of Arabidopsis, comparative genomic studies will allow for the easy identification of relevant genes in Brassicas The identification and characteriza-tion of glucosinolate synthesis genes in Chinese cab-bage would pave the way for further improvement of agronomic traits via genetic engineering In the present study, we report the genome-wide identification of

B rapa glucosinolate synthesis (BrGS) and regulator genes using our B rapa genome sequence in conjunc-tion with the available Arabidopsis sequence We also show that many BrGS genes exist in a small multigene family and that at least 12 desulfoglucosinolate sulfotransferase (BrST) paralogs are present and are differentially expressed

Results BrGS gene identification from cDNA and bacterial artificial chromosome (BAC) libraries

As part of the B rapa genome sequencing project, we produced 127 143 expressed sequence tags (ESTs) from

28 different cDNA libraries that were released to the National Center for Biotechnology Information (NCBI) database and a new B rapa EST database, BrEMD (http://www.brassica-rapa.org/BrEMD/) with microarray data Furthermore, we determined more than 127 000 BAC end sequences, and approximately

589 seed BACs were sequenced and anchored in Arabidopsis whole chromosomes The 65.8 Mb seed BAC sequence information covered approximately 75.3% of the Arabidopsis genome and 40% of the

B rapa euchromatin region [52] On the basis of these databases, homologous genes were identified by a blastn search using the Arabidopsis gene sequence as query All the ESTs that matched each query sequence were aligned to remove the redundant clones, and EST clones containing a start codon were resequenced

to generate the full-length cDNA sequence Through

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Fig 1 Biosynthesis pathways of the three major groups of glucosinolates in B rapa The genes involved in each step are shown Numbers

in parenthesis denote gene copy numbers.

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this alignment, a total of 35 different genes was found

from ESTs In the same way, blastn searches were

per-formed against the BAC sequence databases, yielding

44 different genes, among which 23 overlapped the EST

sequences Thus, a total of 56 individual genes was

identified from both EST and BAC clones, of which

44 contained the full-length coding sequence (CDS)

(Fig 1,Tables 1 and 2) They contain all the homologs

of Arabidopsis except for CYP79F2, FMOGS-OX24,

AOP3 and MYB76 In Arabidopsis, AOP2 and AOP3

are tandemly located on chromosome IV [29]; however,

AOP2was only found in B rapa The same observation

was also made in B oleracea [45] This suggests that duplication occurred in Arabidopsis after its divergence from Brassica Four genes, BrUGT74C1-1, BrST5b-6, BrST5b-4 and BrMYB122-1, appear to be nonfunc-tional as a result of a frame shift or retrotransposon– insertion mutations (Fig 2)

To estimate the total number of putative BrGS genes

in the whole genome of B rapa, a genomic blot was performed using the CYP79F1⁄ F2, CYP79B2 ⁄ B3, CYP83A1 and CYP83B1 genes as probes (see Support-ing information, Fig S1) [53] This analysis predicted the presence of a total of eight genes (two, three, two

Table 1 Comparison of putative BrGS biosynthetic genes with the Arabidopsis orthologs The nucleotide sequence of the coding region was used for comparison analysis; the BrGS gene sequence is from the partial- or full-length CDS; the single percentage indicates the single

B rapa orthologous sequence that was available Most of the genes are full length except those marked with an asterisk.

Glucosinolate pathway

B rapa gene name

Corresponding AGI

No of genes found

Corresponding clones

% Identity At and B rapa

Amino acid side chain

elongation

78.4–87.0

Core structure formation

step

References [24], [25], [26], [27], [28], [29], [31], [57], [58], [59], [79]

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and one copies for each gene, respectively) On the

other hand, a total of seven genes was found from our

database search for those genes, suggesting that the

percentage of BrGS genes identified in the present

study is approximately 87.5%

BrGS gene identity with Arabidopsis and other

Brassica orthologs

BrGS biosynthetic genes share 72–90% nucleotide

sequence identity with Arabidopsis orthologs and 28

genes exist in a small multigene family (Table 1) This

close relatedness is further substantiated by our

phy-logenetic tree analyses (Fig 3; see also Supporting

information, Figs S2–S11) However, most of the

BrGS genes share more than 90% identity with other

Brassica orthologs (Table 3) This is consistent with

the notion that the Brassica species evolved after

divergence from the Arabidopsis lineage Notably,

BrAOP2 has the lowest sequence identity with the

orthologs of Arabidopsis and B oleracea Identities

within the BrGS paralogs are usually higher than

those with Arabidopsis and other Brassica species All

of the BrST5b paralogous genes except BrST5b-4

share more than 80% sequence identity with AtST5b

(Table 4) Identities between BrST5b and AtST5b

(76–86%) are comparable to those between tandem

BrST5b repeats (77–89%) and between nontandem

repeats BrST5b-6 and BrST5b-9 (88%) (Fig 4,

Table 4) This suggests that duplication occurred after

a very recent divergence between Arabidopsis and

B rapa One putative benzoate-CoA ligase gene

BrBZO1pwas identified (see also Supporting

informa-tion, Fig S11) It has a similarity of 81% compared

to both BZO1 and At1g65890

Similar to the biosynthetic genes, BrGS regulator genes share 81–94% nucleotide sequence identity with Arabidopsis orthologs and 15 genes exist in a small multigene family (Table2) Most of the genes are trip-licated, indicating that regulator genes are mostly retained after the Brassica genome triplication

Structure of BrGS genes Ordered assembly of the overlapping sequences of BAC and EST clones yielded the overall gene struc-tures shown in Fig 5 The exon and intron structures

of the BrGS genes were identical to those of Arabidop-sis homologs However, insertion, deletion and intron size variations were commonly noted in BrGS genes One of the two BrC-S lyase genes had a 2 bp deletion

at the last exon, which resulted in a 3¢ truncated pro-tein with a 16 amino acid deletion compared to the Arabidopsis homolog The truncation of 3¢ end exon might alter either gene function or the expression pat-tern in such a way to change feedback regulation, as previously proposed by Gao et al [46] Desulfogluco-sinolate sulfotransferase genes did not have any intron

in both Arabidopsis and B rapa (Fig 5A) The AOP2 structure of B rapa was compared with that of B oler-acea and Arabidopsis All three species contained four exons and three introns, along with considerable changes in intron sizes (Fig 5B) One of the two BrST5a genes contained a 3 bp insertion (Fig 5A), which did not lead to a frame shift mutation

Insertion or deletion often gives rise to a frame shift mutation that causes the loss of gene function This type of mutation occurred in two BrGS genes with pre-mature stop codons immediately after the deletion sites (Fig 2A) Among nine BrST5b paralogs, BrST5b-4

A

B

Fig 2 Structures of the predicted nonfunctional BrGS genes (A) Three of the four carried deletion mutations and (B) the fourth one carried a putative restrotransposon insertion A non-LTR retrotransposon insertion is marked by approximately 6 kb insertion Asterisks indicate the posi-tion of a premature stop codon Thick, thin and dotted lines denote the exon, intron and the gap between BrST5b-4 and BrST5b-x, respectively.

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appears to be a pseudogene because it contains an approximately 6 kb insert of a putative non-long ter-minal repeat (LTR) retrotransposon that encodes a reverse transcriptase (Fig 2B) Transposon insertion mutations in coding sequences or intergenic regions were also previously observed in B oleracea [45] Another gene, BrST5b-x, with only a 150 bp 3¢ end partial sequence, was found to be located in the inter-genic region approximately 500 bp downstream of BrST5b-4 (Fig 2B) However, we did not consider this

as another copy of BrST5b because of the presence of only a small amount of remainder sequence as a result

of a massive deletion event Pseudogenes are assumed

to arise frequently during genome evolution and are often regarded as ‘molecular fossils’ in evolutionary genomics [54] Pseudogenes might be the result of natural selection reducing functional redundancy However, the divergent copies of duplicated genes would be further diversified to evolve for neofunction-alization or subfunctionneofunction-alization [55,56]

Divergent duplication and differential expression

of BrST genes

In comparison with three orthologs in Arabidopsis, desulfoglucosinolate sulfotransferase exists in a small

Table 2 Comparison of putative BrGS regulator genes with the Arabidopsis orthologs The nucleotide sequence of the coding region was used for comparison; the BrGS gene sequences used are either partial or full-length CDS Most of the genes are full length except those marked with an asterisk.

Transcription factors

B rapa gene name

Corresponding AGI

No of genes found

Corresponding clones

% Identity At and B rapa

R2R3-Myb transcription

factors for aliphatic

glucosinolates

R2R3-Myb transcription

factors for indole

glucosinolates

KBrB118H07R &

KBrH078K01R

BR115967

References [36], [37], [38], [39], [40],[41],[42],[43]

Fig 3 Nonrooted neighbor-joining phylogenetic tree of B rapa

desulfoglucosinolate sulfotransferases and Arabidopsis

sulfotrans-ferases Coding sequences of AtST5b were used to identify the

orthologs between these two species because some of BrST5b are

pseudogenes Bootstrap values with 500 replicates are denoted as

percentages.

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Fig 4 Comparative map of the five BACs

containing BrST paralogs and their

counter-parts in Arabidopsis At Chr1, Arabidopsis

chromosome 1; Br R7 (Chr7), B rapa

link-age group R7 (chromosome 7); Br R9

(Chr1), B rapa linkage group R9

(chromo-some 1); Mb, megabase; cM, centimorgan.

The loci of AtST5a,b (At1g74100 and

At1g74090) and BrST counterparts are

indi-cated by oval-shaped bars The loci that

cor-respond to the five Brassica BACs are all

located on Arabidopsis chromosome 1 and

are marked by stick bars Colinear and

non-colinear genes are indicated by dashed and

dotted lines, respectively The location of

KBrB034H04 on the B rapa chromosome

has not yet been established.

Table 3 Sequence similarities between BrGS genes and other Brassica orthologs The nucleotide sequence of the coding region was used for comparison analysis; the highest percentages are shown when a gene has several copies.

B rapa

gene

Gene of other Brassica species

% of

Table 4 Similarity and divergence among desulfoglucosinolate sulfotransferase genes of Arabidopsis and B rapa Values represent the per-centage similarity in the upper triangle area and perper-centage divergence in the lower triangle area as demarcated by the diagonally aligned black squares; full-length CDS was employed for the analyses using DNASTAR software (DNASTAR Inc., Madison, WI, USA).

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multigene family with 12 paralogs in which two EST

clones are not mapped on B rapa (Table 1, Fig 4)

Most of them are clustered in a tandem array, as

shown in the chromosomal loci of BAC clones

(Fig 4) In addition, they are usually clustered

together in the phylogenetic tree (Fig 3)

Two Arabidopsis desulfoglucosinolate

sulfotrans-ferases, AtST5a (At1g74100) and AtST5b (At1g74090),

are involved in the biosynthesis of indolyl and ali-phatic glucosinolates, respectively [57] Nevertheless, they share 80% nucleotide identity and are tandemly located on chromosome 1 (Fig 4) Thus, we examined the expression patterns of BrST genes in different tis-sues by RT-PCR (Fig 6) BrActin1, an actin gene of

B rapa, was used as an internal control to adjust the amount of cDNA template for PCR because it is con-stitutively expressed in all types of tissues Primers were designed from the gene specific untranslated region (see Supporting information, Table S1) All of the genes except BrST5b-4 were expressed in all six ferent tissues, although the expression profiles were dif-ferent Generally, BrST5b was expressed at higher levels than BrST5c but at lower levels than BrST5a Specifically, BrST5b-6 and BrST5b-7 were expressed at the lowest levels because their products were not shown until after 40 cycles of PCR (Fig 6) All of the PCR products were sequenced and were matched to individual gene sequences (data not shown) BrST5a-1

A

B

Fig 5 Structures of representative BrGS genes (A) Comparison

with Arabidopsis orthologs (B) Structural comparison of AOP2

orthologs of Arabidopsis (At), B rapa (Br) and B oleracea (Bo).

Representative BrGS gene structures were composed based on

the full-length genomic, cDNA, or coding sequences of BAC and

EST clones Arabidopsis gene structures were generated according

to NCBI sequence information Each pair of genes was aligned in a

colinear form Positions of introns are indicated by the triangles,

above which intron sizes (bp) are shown as numerals The position

and size of the nucleotide insertion and deletion are also marked as

In ⁄ Del.

Fig 6 RT-PCR analysis of BrST genes in different types of tissues.

L, mature leaf; R, mature root; FB, floral bud; SL, seedling; S, sta-men; C, carpel The PCR products of the BrST genes are approxi-mately 1 kb; BrActin1 is approxiapproxi-mately 450 bp, which serves as an internal control.

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was strongly expressed in all tissues except the stamen.

By contrast, BrST5a-2 was strongly expressed in the

stamen, but weakly in the floral bud and carpel

Over-all, BrST5b paralogs were expressed at a very low level

in the floral bud However, some genes (i.e BrST5b-1

and BrST5b-2) were expressed strongly in the carpel,

whereas others (i.e BrST5b-2, BrST5b-8 and BrST5b-9)

were expressed strongly in the stamen The results

obtained demonstrate that the expression of the

paralogs is not tissue-specific but varies greatly

depending on tissue type In terms of the overall

expression level, mature leaf and root expressed BrST

paralogs at higher levels than other tissues,

demonstra-ting functional redundancy for differential expression

In seedling tissue, BrST5a paralogs were more strongly

expressed than BrST5b paralogs No significant

differ-ences in the expression levels of BrST5a paralogs were

noted between the seedling and mature leaf and root

tissues On the other hand, significant differences

between those tissues were found for the expression

levels of BrST5b paralogs except BrST5b-1 Thus,

expression is developmentally regulated in some BrST5b

paralogs but not in BrST5a paralogs

Discussion

Similarity between B rapa and Arabidopsis

in the glucosinolate biosynthesis pathway

Our B rapa genome sequence database searches

identi-fied the counterparts of most of Arabidopsis

glucosino-late synthesis genes, and they are present in various

copy numbers (Fig 1) Only a few genes that

corre-spond to Arabidopsis CYP79F2, FMOGS-OX24 and

AOP3 were not found in B rapa Thus, a high

colin-earity in the glucosinolate biosynthesis pathway exists

between Arabidopsis and B rapa despite the difference

in gene copy numbers

As the first step, two different genes, BCAT and

MAM, are known to be involved in the chain elongation

of Met-derived aliphatic glucosinolate biosynthesis

BCAT4and BCAT3 enzymes catalyze the deamination

and transamination, respectively [58,59] B rapa

con-tains two BCAT4 paralogs that have 92% nucleotide

sequence identity and are the same size B rapa also

carries two BCAT3 paralogs, one of which has a

full-length CDS MAM enzyme catalyzes the condensation

of acetyl-coenzyme A with a series of

x-methylthio-2-oxoalkanoic acids MAM1⁄ MAM2, two tandem

paralogs found in some of Arabidopsis ecotypes, are

responsible for the first two cycles of chain elongation

[24] MAM3 enzyme catalyzes all the different cycles of

Met chain elongation [25] We identified four MAM

paralogs in the B rapa genome that share approxi-mately 78–87% identities with the Arabidopsis ortho-logs, although we were unable to determine which

of these is individually equivalent to MAM1, 2 and 3 Two of them are not identical in an approximately

200 bp region of the 3¢ ends This is also the case in the

B oleracea MAM (BoGSL-ELONG) gene family [46] and did not affect its enzymatic function equivalent to the Arabidopsis ortholog MAM1 [60] In addition to tissue-dependent differential expression, the members of BrMAM gene family may encode enzymes of different biochemical properties with respect to chain elongation, such as Arabidopsis MAM orthologs Two Arabidopsis genes, IPMS1 and IPMS2, that encode isopropylmalate synthase are similar to the MAM family genes, with 60% similarity in their amino acid sequence [46,61] Nevertheless, they are not involved in Met chain elongation but are involved in leucine biosynthesis Phy-logenetic analysis indicates that the BrMAM genes do not belong to the IPMS family but, instead, belong to the the MAM gene family We were unable to identify the genes responsible for phenylalanine chain elonga-tion, an initial step of aromatic glucosinolate synthesis, because the corresponding genes have not yet been isolated in Arabidopsis and other Brassica species

As the second step, the formation of the glucosino-late core structure is initiated by the conversion of amino acid to the corresponding aldoxime, and this is catalyzed by the CYP79 enzymes [23] Three groups of CYP79 family genes, CYP79F1,2, CYP79B2,3 and CYP79A2, are involved in aliphatic, indolyl and aro-matic glucosinolate biosynthesis, respectively Our database searches indicate two copies of the CYP79B2 and C-S lyase genes and three copies of UGT74C1 in

B rapa, unlike the single copy genes in Arabidopsis Such duplication may necessate a redundant function for tissue- or development-dependent differential expression Excluding two copies of nonfunctional BrST5 carrying frameshift and transposon insertion mutations, eight copies of BrST5 are actually involved

in aliphatic glucosinolate synthesis in B rapa (Table 1, Figs 2 and 4), whereas two copies of the orthologs exist in Arabidopsis The expression level of BrST5 is not only developmentally regulated, but also highly dependent on tissue type (Fig 6) Because sulfonation

is a penultimate step of glucosinolate biosynthesis, the expression of BrST5 may play a crucial role in the tis-sue-specific and developmental accumulation of gluco-sinolates It remains to be determined whether BrST5 transcript levels are correlated with the accumulated levels of indole and aliphatic glucosinolates

The final step of glucosinolate synthesis is side chain modification and, currently, this step is well

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characterized only for aliphatic glucosinolate in

Arabidopsis Glucoraphanin

(4-methylsulfinylbutyl-glucosinolate) is abundant in Columbia but is absent in

the Landsberg ecotype of Arabidopsis This difference is

attributed to the AOP2 gene, whose expression diverts

glucoraphanin into alkenyl-glucosinolate [29] Our

gen-ome database search yielded the presence of a single

copy of AOP2 in B rapa However, two AOP2

quanti-tative trait loci, Ali-QTL3.1 and Ali-QTL9.1, were

recently reported to be involved in determining the type

and concentration of glucosinolates found in B rapa

leaves [62] Consistent with this finding, our Southern

blot analysis indicated the presence of two copies of

AOP2 in B rapa (data not shown) The presence of

AOP2 explains why glucoraphanin was not detectable

in Chinese cabbage [50,51] In B oleracea, two

tan-demly repeated copies of AOP2 contain a 2 bp deletion

at the third exon, which is responsible for the high

accumulation of glucoraphanin (Fig 5B) [45] Brassica

napus, a species resulting from interspecific

hybridiza-tion between B rapa and B oleracea, was reported to

be absent in glucoraphanin [63] This is most likely as

result of the AOP2 gene introduced from B rapa The

content of glucoraphanin in B rapa and B napus could

be elevated by inhibiting AOP2 expression via antisense

or RNA interference approaches

Similarity of the genes controlling glucosinolate

biosynthesis between B rapa and Arabidopsis

B rapa contains the orthologs of the Arabidopsis

glucosinolate regulators, except MYB76 (Table 2)

Unlike Arabidopsis, they are normally triplicated,

con-sistent with the Brassica genome triplication event The

duplication and divergence of the regulators in a small

multigene family along with multiple duplications of

their target biosynthesis genes may result in phenotypic

variation AOP2⁄ AOP3 null accessions of Arabidopsis

were shown to accumulate an increased level of the

precursor methylsulfinylalkyl glucosinolate but also a

considerably lower level of total aliphatic

glucosino-lates than the accessions with a functional AOP2 allele,

which has been explained by the differential feedback

regulation of transcript regulators MYB28, 76 and 29

by the side chain modification end products [29,30,64]

Similarly, epistatic interactions between AOP2 and

transcript regulators MYB28 and MYB29 may exist in

B rapa

BrGS gene duplication

The Brassica genome is believed to have triplicated

soon after its divergence from Arabidopsis [65–67] The

genome sizes of B rapa (550 Mb) and B oleracea (696 Mb) are more than four- and five-fold greater than that of Arabidopsis (125 Mb), respectively [68,69] This could be explained in part by the presence of big-ger gene families as a result of genome diploidization, segmentation or gene duplication In B oleracea, genome rearrangement is commonly followed by gene loss, fragmentation and dispersal [70] Many gene duplications arose as a result of the triplication event, and those genes involved in signal transduction or tran-scriptional control are more extensively retained than others during the evolution process [70] Some tandemly duplicated genes in B rapa and B oleracea are likely to

be the result of an unequal crossover during the rear-rangement process after Brassica genome triplication [45,46] Approximately 14% of B rapa genome is esti-mated to consist of transposable elements, the majority

of which are retrotransposons [69] It has been proposed that gene duplication also is facilitated by retrotranspo-son carrying a LTR [71] BrST is a good example of a multigene family with tandem arrays of genes in

B rapa The genes adjacent to two tandem repeats, BrST5b-1 and BrST5b-2, were colinear with their Arabidopsiscounterparts, and all the other BrST genes jumped to completely new positions (Fig 4) BrST5b-1,

3, 4 and 5 were found to be flanked by LTR Copia-like retrotransposons (data not shown) BrST5b-4 was dis-rupted by insertion of a putative non-LTR retrotrans-poson and shares 89% sequence identity with BrST5b-5

in a tandem array They also are tandemly arranged with BrST5b-3 in the same BAC clone, but with lower sequence identities compared to that between them This suggests two consecutive steps of duplication occur at the same locus

Sequence comparison of glucosinolate synthesis genes reflects evolution of Brassica lineage Soon after divergence from the Arabidopsis lineage and genome triplication, extensive interspersed gene loss or gain events and large-scale chromosomal rearrange-ments gave rise to three basic diploid species: B rapa (AA genome), Brassica nigra (BB genome) and B oler-acea (CC genome) [66] Our data support this pre-sumptive evolution order; BrGS sequence similarities among the Brassicas (mostly > 90%) are normally higher than those between Brassica and Arabidopsis (mostly 80–90%) Individual tandem repeats or dis-persed duplication events are indicative of the self-rear-rangements occurring within each species A convincing example is that AOP3 is only present in Arabidopsis and that AOP2 is tandemly duplicated in

B oleraceabut not in B rapa Even within B oleracea,

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