© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

ARTICLES

Comparative analysis of chimpanzee and human Y
chromosomes unveils complex evolutionary pathway
Yoko Kuroki1, Atsushi Toyoda1, Hideki Noguchi1,2, Todd D Taylor1, Takehiko Itoh3, Dae-Soo Kim4,
Dae-Won Kim4,5, Sang-Haeng Choi4, Il-Chul Kim4, Han Ho Choi4, Yong Sung Kim4, Yoko Satta6,
Naruya Saitou7, Tomoyuki Yamada2, Shinichi Morishita2, Masahira Hattori1,8, Yoshiyuki Sakaki1,
Hong-Seog Park4,5 & Asao Fujiyama1,9
The mammalian Y chromosome has unique characteristics compared with the autosomes or X chromosomes. Here we report thefinished sequence of the chimpanzee Y chromosome (PTRY), including 271 kb of the Y-specific pseudoautosomal region 1 and12.7 Mb of the male-specific region of the Y chromosome. Greater sequence divergence between the human Y chromosome(HSAY) and PTRY (1.78%) than between their respective whole genomes (1.23%) confirmed the accelerated evolutionary rateof the Y chromosome. Each of the 19 PTRY protein-coding genes analyzed had at least one nonsynonymous substitution, and 11
genes had higher nonsynonymous substitution rates than synonymous ones, suggesting relaxation of selective constraint, positive
selection or both. We also identified lineage-specific changes, including deletion of a 200-kb fragment from the pericentromericregion of HSAY, expansion of young Alu families in HSAY and accumulation of young L1 elements and long terminal repeat
retrotransposons in PTRY. Reconstruction of the common ancestral Y chromosome reflects the dynamic changes in our genomes
in the 5–6 million years since speciation.

The completion of the sequencing of the human genome has demonstrated the importance of comparative studies for deciphering theinformation and functions written in our genomes1,2. As chimpanzees
are evolutionarily the closest living species to humans, various
studies3–11 have aimed to understand the genetic basis of the similarities and differences between the two species. Sequence-based genomewide studies have defined with precision the nucleotide difference
between human and chimpanzee as 1.23% (refs. 4,5,8). Owing to thishigh similarity in the sequences, it was essential to produce highquality sequence data in order to delineate species-specific changes
accumulated after the species diverged10.
The mammalian sex chromosomes are thought to have originatedfrom a pair of autosomes that ultimately evolved into the X and Y
chromosomes through (i) the incorporation of genes controlling sex
determination and (ii) the acquisition of mechanisms to prevent
recombination between the X and Y chromosomes and compensate
for the difference in gene dosage of the X chromosome–encoded genes
between male and female12–17. Thus, unlike other chromosomes,
modern-day Y chromosomes have undergone numerous structuralchanges without correction through recombinatorial processes17–21.
We have reported previously that chimpanzee BAC clones
mapped poorly onto the human Y chromosome compared with otherchromosomes4. Thus, we produced a high-quality sequence of the Y
chromosome for the same male chimpanzee that we had previously
analyzed for the chimpanzee chromosome 22 (PTR22; ref. 10). In thisstudy, we sequenced approximately 12.7 Mb of PTRY, which corresponds mostly to the X-degenerate region of HSAY and partly to thechimpanzee ampliconic region (Fig. 1). Precise alignments produced
from the PTRY sequences and the corresponding sequences of HSAY
allowed us to carry out comparative analyses with HSAY19, HSAX20
and the only other finished human-chimpanzee chromosome complement of HSA21 and PTR22 (ref. 10).
RESULTS
Analysis of the PTRY sequence
We isolated clones from the whole-genome BAC library and Y-specific
BAC and fosmid libraries originating from a single male chimpanzee(named Gon) that we had previously analyzed for PTR22 (ref. 10).
The minimum tiling path, at the time of data freeze for this analysis,
consisted of 96 minimally overlapping clones forming four clone
contigs covering 905,338 bp of PTRYp and 10,074,253 bp of PTRYq,
including 271 kb of the Y-specific pseudoautosomal region 1 (PAR1)
sequence at the end of PTRYq (Figs. 1 and 2, Table 1, Supplementary
Table 1 and Supplementary Methods online). The accuracy of the

1RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan. 2Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-0882, Japan.
3Mitsubishi Research Institute, Tokyo 100-8141, Japan. 4Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333,

Korea. 5University of Science and Technology, Daejeon 305-333, Korea. 6The Graduate University for Advanced Studies, Hayama 240-0193, Japan. 7National
Institute of Genetics, Mishima 411-8540, Japan. 8Kitasato University, Sagamihara 228-8555, Japan. 9National Institute of Informatics, Tokyo 101-8430, Japan.
Correspondence should be addressed to H.-S.P. (hspark@kribb.re.kr) or A.F. (afujiyam@nii.ac.jp).
Received 18 July 2005; accepted 30 November 2005; published online 1 January 2006; corrected after print 29 January 2006 (details online); doi:10.1038/ng1729

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Figure 1 Schematic view of the sequenced area and major landmarks on
chimpanzee chromosome Y. Although in the text we followed a previously
reported method21 for the designation of the p- and q-arms of HSAY and
PTRY, in this figure, for simplicity, PTRY is inverted, and the PAR1 regionsof each chromosome are aligned. From FISH imaging and from fluorescencevalues obtained from flow karyotyping, we estimated the size of PTRY as
23 Mb (data not shown). P1–P8, P6+ and CSP1 indicate the positions of
the palindromic structures.

PAR1 (2.7 Mb)
P6+X-transposed region (3.7 Mb)

P7
HSAYp

PTRYq
P8

CSP1
Centromere (1 Mb)© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

P8
P7
P6

200 kb duplication

P4, P5
HSAYq

PTRYp

P1, P2, P3

PTRY (estimated length ~23 Mb)
Heterochromatin (~30 Mb)

Regions analyzed in this study
X-degenerate regions
Ampliconic regions

PAR2 (0.33 Mb)
HSAY (~60 Mb)

sequence was estimated at 99.9998%. One of two internal clone gaps
(between PTB-143L19 and PTB-101K22) was subsequently closed
after the data freeze. The remaining gap, sized as 15 kb by fiber–
fluorescent in situ hybridization (FISH), lies within a palindromic
structure on PTRYq (between PTFY-072J06 and PTFY-037C19). The

a
b
c
d

CSP1

200 kb dup.
R01
R02

Synteny blocks

PTRYq sequence now covers 10,243,335 bp including additionalsequences from the chimpanzee ampliconic region.
Owing to the limited availability of chimpanzee cDNA sequences,the positions of the chimpanzee genes were inferred from themanually annotated HSAY genes and were mapped onto PTRY
using the HSAY-PTRY sequence alignments (9,006,686 bp in total;
see Methods). Another gene map, including annotation inferred from
HSAY at the National Center for Biotechnology Information (NCBI),is provided separately (Supplementary Fig. 1 online). Altogether, we
identified 32 genes (19 protein-coding genes and 13 non–proteinencoding RNAs) and 59 pseudogenes in the analyzed regions of PTRY
(Supplementary Table 2 online). All possible PTRY transcripts inthese regions corresponding to annotated HSAY pseudogenes werealso identified as pseudogenes (that is, their ORFs were disrupted). We
mapped 19 protein-coding genes on our sequence, whereas 20 coding
genes were identified on the corresponding regions of HSAY (Table 2).
This difference comes from the lack of a complete CD24L4 genesequence in PTRY. Using comparative PCR analysis, we further
P8

R03 R05 R07
R04 R06

P6+

P7

R11 R13 R15
R10 R14

R09

R08

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

100
80
60
LINE
40
20
LTR
0
Other
0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

1.0

2.0

3.0

4.0

5.0

6.0

1.0

2.0

3.0

4.0

5.0

6.0

PAR1
R17
R16

10.0

11.0

12.0

9.0

10.0

11.0

12.0

8.0

9.0

10.0

11.0

12.0

7.0

8.0

9.0

10.0

11.0

12.0

7.0

8.0

9.0

10.0

11.0

12.0

R12

Genes
Pseudogenes
Repeats (%)

SINE

e

G+C (%)

50
45
40
35
30

f

0.0
Divergence (%)

g

3.5
3.0
2.5
2.0
1.5
1.0
0.0

0.20
0.16
Ci/Hd 0.12
0.08
Cd/Hi
0.04
0.00

Indels (%)

h0.0
Indels (large)

Figure 2 Features of the PTRY sequence. (a) Alignment blocks with human chromosome Y. (b) Mapped genes according to the VEGA HSAY annotation.
Genes on the plus and minus strands are located above and below the axis, respectively. (c) Pseudogenes according to the VEGA HSAY annotation.
(d) Interspersed repetitive sequence content. Window size: 100 kb. (e) G+C content. Window size: 100 kb. (f) Divergence rate with human chromosome Y.
Window size: 100 kb. (g) Indel (o10 bp) rate with human chromosome Y. Window size of 100 kb. Ci/Hd indicates chimpanzee insertion or human deletion.
Cd/Hi indicates chimpanzee deletion or human insertion. (h) Large indels (4250 bp) are indicated by rectangles. The length of the base of each triangle
indicates indel size.

2

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Table 1 Statistics on HSAYa and PTRY
HSAY

Size (bp)b
G+C content (%)© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

Repeats
SINEs

All
AluY

PTRY

All

Aligned regions

All

Aligned regions

24,871,691
39.85

9,678,597
39.48

10,950,101
39.58

10,197,059
39.61

NumberLength (bp)

NumberLength (bp)

NumberLength (bp)

NumberLength (bp)10,0891,288

2,484,596
366,9893,965
457

993,015
131,117

4,327
534

1,083,963
153,863

4,083
490

1,023,286
141,103

AluYa5,AluYa8,AluYb8,AluYb9

97

29,022

46

13,619

2

526

2

526

6,332
115

6,280,931
303,8542,519
392,730,875
123,8792,769
592,986,580
175,9852,622
572,820,027
170,953

LTRs
DNAs

4,701
1,487

4,393,986
407,6772,150
759

1,858,604
199,472

2,428
821

2,103,312
217,370

2,307
781

2,007,340
204,604

RNA
Satellites

55
1,161

5,424
1,110,631

17
170

1,892
188,879

17
309

1,857
270,957

15
200

1,707
197,966

OthersSimple repeats/low

15
7,842

17,013
660,735

7
2,899

7,671
229,318

9
3,268

9,196
246,199

7
3,037

8,725
232,178complexity regions
Total

31,682

15,360,993

12,486

6,209,726

13,9486,919,434

13,052

6,495,833

LINEs

All
L1HS, L1PA2

(%)

61.76

64.16

63.19

63.70

aHSAY data was taken from ref. 19. Both the whole and aligned sequences were analyzed using the same parameters (see Methods). bNs are not included.

confirmed that CD24L4 was inserted in the human lineage after the
speciation of human and chimpanzee (Supplementary Fig. 2 andSupplementary Methods online).
Many genes on the Y chromosome are reported to have evolved
rapidly and to have undergone positive selection22. We tested thishypothesis for the 19 PTRY protein-coding genes by comparison of
nonsynonymous and synonymous substitutions between HSAY andPTRY (Table 2). All genes analyzed in this study were found to have atleast one nonsynonymous substitution in their coding regions withthe exception of GYG2 isoform 2, which has none (Supplementary
Table 3 online).
Comparative analysis of the PTRY sequence
We first constructed a whole base-to-base sequence alignment between
PTRY and HSAY (see Methods) to compare structural differences. The
overall substitution level between PTRY and HSAY is 1.78% (excluding
insertions or deletions (indels)). This value decreases to 1.66% whenrepetitive sequences are excluded. In contrast, the values are 1.83%
and 1.91% in L1 long interspersed nuclear elements (LINEs) and Alu
short interspersed nuclear elements (SINEs), respectively (Table 1 andSupplementary Table 4 online). In all cases, the nucleotide divergence
between HSAY and PTRY exceeds that of HSA21 and PTR22 (1.44%,
excluding indels; 1.38%, L1/LINEs; 1.81%, Alu/SINEs)10. This higher
substitution rate between the Y chromosomes confirms the accelerated
evolutionary rate of the Y chromosome, as previously reported23–25.
This is presumably a consequence of the large number of cell divisions
in the male germ line (Supplementary Note online).
Notably, the correlation coefficient between base substitutions andindels (about 17,400 sites; most of them are short, as described below)
is 0.40, which is considerably higher than that between substitutionsand G+C content (0.26; Supplementary Fig. 3 online). Because amolecular clock exists for substitutions and indels26, this correlation
might indicate that the evolutionary or mutation rate for bothsubstitutions and indels varies from region to region of the nonrecombining Y chromosome. To examine this hypothesis, we compared the observed distribution of nucleotide differences (within

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10-kb windows) and expected differences under the Poisson distribution (Supplementary Fig. 3). The results show that the observed
distribution is considerably more varied than the Poisson expectation.
This discrepancy suggests that the evolutionary or mutation rate varies
depending on the region of the Y chromosome sequence, although
there is essentially no recombination. If this finding applies to otherchromosomes, it will have significant implications on many evolutionary analyses, such as correlation of substitution and recombination rates and estimation of ancestral population size.
As the PTRY sequence analyzed in this study originated from asingle male animal, Gon10 (PTB library), we compared intraspecies
nucleotide diversity using the sequences in the public database51(Supplementary Table 5 online). The result shows relatively lower
nucleotide diversity in a pairwise comparison with two other animals,
Clint (CHORI-251 library) and Donald (RP-43 library), 0.0422 ±0.0006% (s.e.m.) and 0.0343 ± 0.0012%, respectively. This extent ofdiversity is lower than the result (0.067%) from a previous study27.
The most likely explanation to this difference is that the current
analysis is most likely from one subspecies, Pan troglodytes verus(P. t. verus), whereas the former result included the two othersubspecies (Supplementary Note).
From the intra- and interspecies comparisons, we detected thepresence of several blocks around the boundary of PAR1 and the malespecific region of the Y chromosome (MSY), in which nucleotide
differences between HSAY and PTRY were significantly higher than inother regions (Fig. 3). It has been reported recently28 that there is a
gradient of silent substitution rates in the human PAR1 region. It
would be interesting if such an L1-rich region were to function as an
insulator that prevented homologous recombination between the X
and Y chromosomes proceeding beyond the PAR1-MSY boundary(Supplementary Note).
Identification of lineage-specific events
Indels are one of the major types of events that have caused structuraldifferences between the human and chimpanzee genomes1,3,8–10,29–31.
In this study, we compared PTRY and HSAY using sequence

3

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Table 2 Comparison of HSAY and PTRY genes located in the male-specific regions
Human
Isoform

CDSc

RPS4Y2 a
EIF1AY

1
1

C
C

JARID1D

2
1© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

Gene

Length (nt)

Length (aa)Length (nt)

1
1,3

792
435

263
144

C
C

2
1,3

384
4620

127
1539

4608

2
3

C
P

2
4

4449
4429

1482
1475

4

P

5

880

292

CYorf15B

5
1

P
C

6
1,2

1276
546

424
181

CYorf15A
CD24L4b

2
1

C
C

2
1

396
243

131
80

AC002992.5(GYG2-like)

1
2

C
c

1,2
3

192
195

3
4

c
c

4
5

USP9Y

1
2

c
p

DDX3Y

1
2

Position
Start

End

Strand

Ks

Ka

Ka/ks

3255247
3443800

3280582
3460706––

0.00401
0.00705

0.01256
0.003483.1322
0.49361535

3443275
4005775

3460706
4044929–+0.007900.01272

0.00397
0.00356

0.50250.2799

4437
4417

1478
1471

4005937400577540449244044270++0.01192
0.01192

0.003700.003440.31040.2886868

288

4041398

4043150+

0.013080.004710.3601144

474005987414921440293854162932+–

0.023280.00000

0.004190.00000

0.1800inf

41649484188018–0.01478

0.02197

1.4865

–

–

63
64

57470725772349

58130625812998––

0.02818
0.02818

0.01691
0.00000

0.60010.0000

360
291

119
96

57948935798765

58130625812978––0.04083
0.02549

0.012020.005400.29440.2118

1,2
3

7668
713

2555
236

6110319625066062644766263247++

0.008220.00832

0.01151
0.007681.40020.9231

c
p

1,3,4
2

1983
673

660
223

630811463081246322604
6317902++0.00608
0.00000

0.007640.01377

1.2566
inf

3
1

p
c

5
1,2

750
4044

249
1347

63097426675101

6318698
6909521+–0.004210.010400.012390.00885

2.94300.8510

2
3

c
c

3
4

3723
3240

1240
1079

6724040674911669095186909518––

0.011310.01371

0.00805
0.00989

0.71180.7214

TMSB4Y

4
1

c
c

5
1,2

624
135

207
44

682212071632396908834
7165658–+

0.014400.06752

0.015800.02001

1.09720.2964

VCY1B
VCY

1
1

c
c

1,2
1

378
378

125
125

74739297506529

74749127507516–+0.01784
0.01784

0.05604
0.05604

3.14133.1413

NLGN4Y

1
2

c
c

1
2,4

1947
2451

648
816

8783257
8785183

90771859076187––

0.03518
0.03373

0.00830
0.008940.23590.2650

3
4

c
p

3
5

2622
710

873
235

776

257

878518388937299076187
8986249––

0.032850.02625

0.00950
0.01030

0.2892
0.3924

PRKY
BL1Y

1
1

c
c

1,2
1,2,3,4

834
1569

277
522

414

137

10975071
11262846

11083898
11452127––

0.02292
0.053680.03046
0.01320

1.32900.2459

AMELY

1
2

c
c

1,3
2

579
621

192
206

11651925
11653343

11660023
11659868++

0.005450.005070.00871
0.00808

1.5982
1.5937

ZFY

1
2

c
p

1,2
3

2406
274

801
90

11847686
11868852

11897737
11897513––

0.008150.00000

0.003560.010700.4368
inf

RPS4Y

1
2

c
p

1,2
3

792
787

263
261

11964546
11964640

11989729
11989295––

0.020160.020240.00155
0.00157

0.07690.0776

SRY

1

c

1,2

615

204

12047711

12048555+

0.00504

0.01568

3.1111UTY

Variant

Chimp

5601

753

375
375

Length (aa)

1866

250

124
124

inf, infinite. aRPS4Y2, ribosomal protein S4, Y-linked 2, is defined as a pseudogene in NCBI Entrez Gene. bCD24L4 is a member of the CD24 family (NCBI Entrez Gene). The other four CD24
family members are found in both human (CD24, 6q21; CD24L1, 1p36; CD24L2, 15q21-q22; and CD24L3, chr20; NCBI Entrez Gene) and chimpanzee (exact positions unclear). cc: complete
coding sequence (CDS); p: partial coding sequence.

alignments (excluding the ampliconic region), emphasizing both thedifference between the two Y chromosomes and the difference
between the autosomes and the Y chromosomes. For this purpose,
we extracted all the gaps from the sequence alignment as potential
indel sites (Methods). Most of the indels were found to be small andto account for 88% (1–10 bp) or 98% (1–100 bp) of the total gaps.
The largest event identified was a 3.7-Mb insertion into HSAY. This is
known as the X-transposed region and is thought to have occurred
after the speciation of humans and chimpanzees19,20.
We and others have previously reported that a copy of a 200-kb
paralogous fragment is missing from the pericentromeric region of
PTR22q10,32,33. This 200-kb segmental duplication originated from the
HSA21q22.1 region through transposition to the pericentromeric4

regions of HSA18p11, HSA13q11, HSA21q11.1 and the ancestralchromosome(s) of HSA2q and the corresponding regions in thegreat apes32,33. It has been reported that the 200-kb fragment is notfound on HSAY and PTRY; however, through sequence comparison,
we identified another copy of this fragment at the pericentromericregion of PTRYp (Figs. 1 and 2). In contrast, the corresponding
sequence was not found on HSAY. A neighbor-joining tree showedessentially the same tree topology as previous reports except for an
acceleration in the substitution rate (that is, a longer branch) of the
PTRY copy (Supplementary Fig. 4 online). As the copy on PTRY
shares a greater abundance of base substitutions with the copies on
PTR22 and HSA21q22.1 than with those of other pericentromericcopies (98 versus 2, respectively), it is most likely that the PTRY copy

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PAR1

a

XG

RPS4Y

ZFY
–200 –180 –160 –140 –120 –100

–80

–60

–40

–20

0

20

SRY

CD99
40

60

80

100

180

220

240

260

280

300 kbPTBY-001M14

BS000657
PTBY-009O17

BS000560b

200

BS000622
PTBY-002C07

BS000614© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

160

PTB-461C11

PTB-475G01c

140BS000556
PTBY-009K01

PTB coverage

BS000612

CH251-395K13
CH251 coverage

120

CH251-490L21
AC146189
CH251-549F12

AC146206
AC146174

Sequence divergence
between PTRY and HSAY (%)

3.5
3.0
2.5
2.0
1.5
1.0
–200 –180 –160 –140 –120 –100

dSequence divergence
between chimpanzee individuals (%)

–80

–60

–40

–20

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300 kb

–80

–60

–40

–20

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300 kb

–80

–60

–40

–20

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300 kb

–80

–60

–40

–20

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300 kb0.00050.00040.00030.00020.00010.0000–200 –180 –160 –140 –120 –100e

G+C (%)

50
45
40
35
30

f

–200 –180 –160 –140 –120 –100
Repeats (%)

100
80

SINE
LINE
LTR
Other

60
40
20
0
–200 –180 –160 –140 –120 –100

Figure 3 Comparison of the PAR1 and MSY regions of PTRY. The boundary between PAR1 and MSY is indicated by a red vertical line. The region to theright of the boundary is PAR1. (a) PTB clone coverage. (b) CH251 clone coverage. (c) Divergence between PTRY (PTB clones) and HSAY. Window size:
10 kb. (d) Divergence between PTB clones and CH251 clones. Window size: 10 kb. (e) G+C content. Window size: 10 kb. (f) Interspersed repetitive
sequence content. Window size: 10 kb.

was duplicated from the ancestral PTR22/HSA21q22.1 copy.
The presence of the 200-kb fragment on PTRY was further confirmed by FISH analysis (Supplementary Fig. 4). Through comprehensive sequence comparison, we concluded that it is most likelythat duplication of the HSA21q22.1/PTR22 copy occurred on
the ancestral Y chromosome before the speciation of humans
and chimpanzees and that the copy on HSAY was lost thereafter(Supplementary Note).
LINEs and long terminal repeat (LTR) retrotransposons comprisethe major component of repetitive sequences on both PTRY and
HSAY19 (Table 1). In an extreme case, we found that the LTR12B/D
retrotransposon is repeated 36 times within a 260-kb insertion in
HSAY at the site corresponding to the 3.7 Mb position of the PTRY
sequence (Fig. 2). Furthermore, we found at least 14 integration sites,
ranging from 4.5 kb to 9.0 kb in size, of chimpanzee endogenous
retroviruses on PTRY34–36. We were unable to find such sequences in
the human genome (cutoff value of identity was 90%). Twelve of the
14 integration sites share sequence identity greater than 95% and arelikely to belong to the same viral group (CERV1 and CERV2)
previously reported on chimpanzee chromosome 7. The remaining
two copies, located at internal ends of the P8 palindrome arms, were

NATURE GENETICS ADVANCE ONLINE PUBLICATION

found to be completely identical, suggesting conversion of sequences
between the palindrome arms.
By comparing HSA21 and PTR22, we have shown previously thatthe human genome experienced almost ten times more Alu insertions
than the chimpanzee genome, and that the mode of Alu insertion is
distinctly different between the two species; that is, the observed ratioof the insertion frequencies between AluYa to AluYb is approximately
1:2 (ref. 10). To explore whether or not such phenomena are also
observed on the Y chromosomes, we selected 62 young Alu elementsfrom the sequence alignments for further analysis (Methods andSupplementary Table 6 online). In contrast to HSA21, the AluYa5
subfamily forms a larger cluster than the AluYb subfamily on HSAY
(Fig. 4a). Thus, it seems likely that the insertions in autosomes have ahigher chance of removal, possibly through recombination, although
we cannot rule out the possibility that the insertion frequency was
higher in the Y chromosomes. It is also notable that HSAY contains alarger number of young AluY subfamilies than HSA21 (at approximately a 2:1 ratio) although the total content of SINEs is the same
(approximately 10%) among these chromosomes10 (also reported inthis study), suggesting that roughly half of the young Alu elements
have been removed from HSA21. In contrast, the number of AluYa

5

ARTICLESa

Hl_61_AluY

Hl_18_AluYg6

Hl_31_AluY

Hl_9_AluY

Hl_3_L1HS
Hl_16_L1HS
Hl_25_L1HS
Hl_10_L1HS
Hl_7_L1HS
Hl_29_L1HSb

Hl_29_AluYh9
Hl_32_AluYh9

Cl_13_AluY
Cl_14_AluY

Hl_11_AluY

Cl_26_AluY

Hl_19_AluY

Hl_43_L1PA2

Cl_18_AluY
Cl_19_AluY
Cl_28_AluY

Hl_8_AluY

Cl_11_AluY
Hl_12_AluYd8
Hl_15_AluYd8
Hl_20_AluYb9
Hl_51_AluYb9
Hl_33_AluYb9
Hl_36_AluYb9
Hl_49_AluYb9
Hl_56_AluYb9
Yb
Hl_68_AluYb9
Hl_46_AluYb9
Hl_58_AluYb9
Hl_45_AluYb9
Hl_21_AluYa5
Hl_43_AluYa5
Hl_55_AluYa5
Hl_42_AluYa5
Hl_67_AluYa5
Hl_13_AluYa5
Hl_30_AluYa5
Hl_48_AluYa5
Hl_28_AluYa5
Hl_35_AluYa5

Hl_47_L1PA2
Hl_18_L1PA2
Hl_42_L1PA2
Hl_45_L1PA2
Cl_7_L1PA2
Hl_41_L1PA2

Hl_14_AluY
Cl_27_AluY

Cl_3_L1PA2
Cl_51_L1PA2© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

Yd

Ya

Hl_10_AluYa5
Hl_54_AluYa5
Hl_26_AluYa5
Hl_34_AluYa5

Hl_66_AluYa5
Hl_50_AluYa5
Hl_40_AluYa5
Hl_41_AluYa5
Hl_53_AluYa5
Hl_16_AluYa5

Hl_52_AluYa5
Hl_22_AluYa5
Hl_38_AluYa5
Hl_23_AluYa5
Hl_25_AluYa5
Hl_27_AluYa5
Hl_60_AluYa5

Hl_3_AluY_16
Hl_5_Alu
Hl_7_AluY
Hl_39_AluY

Hl_44_L1PA2
Cl_22_L1PA2
Cl_4_L1PA2
Cl_52_L1PA2

Hl_24_AluYb9

Cl_42_L1PA2
Cl_49_L1PA2
Cl_53_L1PA2
Cl_46_L1PA2
Cl_8_L1PA2
Cl_6_L1PA2
Cl_9_L1PA2
Cl_50_L1PA2
Cl_55_L1PA2
Cl_48_L1PA2
Cl_10_L1PA2
Cl_2_L1PA2
Cl_47_L1PA2
Cl_45_L1PA2

Hl_4_AluYa5

0.01

Cl_18_L1PA2

Hl_1_AluYa8
Hl_37_AluYa8
Hl_17_AluYa5

Cl_3_AluY
Cl_5_AluY
Cl_7_AluY
Cl_10_AluY

Cl_29_AluY
Cl_24_AluY
Cl_25_AluY
Cl_1_AluY

Cl_9_AluY
Cl_31_AluY
Cl_30_AluY
Cl_15_AluY
Cl_12_AluY
Cl_17_AluY
Cl_8_AluY
Cl_16_AluY
Cl_23_AluY
Cl_120_AluY
Cl_2_AluY
Cl_4_AluY
Cl_20_AluY
Cl_6_AluY
Hl_6_AluY
Hl_57_AluY
Hl_59_AluY
Hl_44_AluY

Cl_21_AluY

0.01

and AluYb subfamilies is markedly lower in PTRY (two in PTRY
versus 46 in HSAY; Table 1), confirming previous reports on expansion of these specific Alu subfamilies in the human lineage10,31,37,38.
The human and chimpanzee Y chromosomes are enriched forLINEs (25% and 27% of the total sequence, respectively (ref. 19 andthis study)), as is the X chromosome (29%; ref. 20), whereas LINEs
make up only 17% of the total sequence in HSA21 and PTR22(ref. 10). Although most of these LINEs must have been inheritedfrom a common ancestor, we confirmed that the content of young L1
elements (L1PA2 and L1HS) within the entire LINE sequences washigher in both HSAY and PTRY (4.5% and 6.1%, respectively, incontrast to 1.4% for both HSA21 and PTR22; refs. 1,10). However, wefound that the L1 elements integrated into PTRY were mostly fromthe L1PA2 subfamily, whereas they were mostly from the L1HS
subfamily in HSAY, suggesting that there was a period of time when
L1PA2 actively expanded in the chimpanzee lineage (Fig. 4b). We also
carried out comparative PCR analysis to identify the lineage specificityof these events (Fig. 4 and Supplementary Methods). As we reported
previously10, most of the insertions were found to be related torepetitive sequences, and, in contrast, most of the deletions were not(Supplementary Note).
Global structural changes
As most of the PTRY sequence analyzed in this study corresponds to
the X-degenerate region, and the structure of the X chromosome isstrongly conserved among mammalian species20, evolution of theregion could be described as a process of structural changes from

6

Figure 4 Evolutionary relationship between inserted repetitive elements.
(a,b) Neighbor-joining tree of (a) young Alu families and (b) young L1
families inserted into PTRY (blue) and HSAY (red) after speciation. The
scale indicates an evolutionary distance of 0.01. Sequences with green
stars indicate confirmation of lineage specificity (either insertion into HSAY
or PTRY) through comparative PCR analysis (experimental details can befound in Supplementary Methods). Ya, Yb and Yd designate clusters ofspecific Alu subfamilies in human.

the corresponding regions of the current human X chromosome20.
Consequently, we inferred the evolutionary process through computational calculation (see Methods) and reconstructed the common
ancestral Y chromosome shared by human and chimpanzee (Fig. 5
and Supplementary Fig. 5 online).
A majority of the structural differences between HSAY and PTRY
can be explained by single inversion events that occurred in theancestral Y chromosomes of each lineage. In the case of HSAY, we
speculate that the inversion event occurred around the NLGN4Y-STS
region (Fig. 5c), which concurrently split synteny blocks 5 and 7 into
5-h1/h2 and 7-h1/h2, respectively. This model is in agreement with aprevious report39. Similarly, an inversion event that occurred in PTRY
split synteny blocks 1 and 4¢ into 1-p1/p2 and 4¢-p1/p2, respectively.
As a result, these rather simple inversion events can explain the
fragmentation of the syntenic regions, found with different orders
and orientations, between HSAY and PTRY.
We identified counterparts of the three large-scale palindromes (P6,P7 and P8) of HSAY19 in the PTRY sequence (we also found a P5-likesequence in PTRY, but not in the contiguously sequenced region of theminimum tiling path). In addition, we identified one chimpanzeespecific palindrome (CSP1; Fig. 1, Supplementary Fig. 6 and Supplementary Note). The HSAX sequences corresponding to P4 and P5
do not form palindromes, and the absence of P4 in chimpanzee has
been previously reported40. P7 is relatively small and has nearly aidentical structure in human and chimpanzee. In contrast, weobserved significant differences between the human and chimpanzee
forms of P6 and P8 (Fig. 6). Chimpanzee P6, at 760 kb, is larger than

ADVANCE ONLINE PUBLICATION NATURE GENETICS

ARTICLESa X/Y ancestor (by analogy with HSAX)VCX2XG GYG2

PRKX

5.0

1

2

3

NLGN4X

4

VCX3A

STS

5

VCX

6

7

8

KAL1

VCX3B

TBL1X

9

10

AMELX
10.0 (Mb)
11

12

13

© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

PAR1

b Common ancestral Y
12

13

10

1

11

(0.1 Mb)

9

8

7

6

5

4′

3

2

(1.2 Mb)

c HSAY
Centromere
12 13 10-h0

1-h1 111-h2

9

8 7-h1

5-h1

6

4′

7-h2 5-h2

3-h1(5 Mb)(3.7 Mb)(1.4 Mb)
P8

7.0
AMELY
TBL1Y

PRKY

3-h2 2P7

13.0
GYG2-like
VCY1B
VCY

15.0

P6

P5 P4
(Mb)

NLGN4YSTS(pseudogene)d PTRY
P6+

12 13

10

1-p2

P7

4′-p2

4′-p3

5

Centromere

P8

6

7

8

9

11

1-p1 4′-p1

3

2
200 Kb dup.

copy
AMELY
TBL1Y

PRKY

10.0

NLGN4YSTS(pseudogene)

VCY GYG2-like
VCY1B

5.0 (Mb)

Figure 5 Synteny blocks in the sequenced region of PTRY and comparison with HSAY. Synteny blocks in PTRYq and HSAY identified through comparison
with the corresponding regions of HSAX are shown as color-coded triangles. The scale (Mb) in the figure is variable from region to region. (a) Synteny
blocks from HSAX, which is regarded as the ancestor of the X and Y chromosomes, are shown. Correlation with the block numbering system reported
previously20 is shown in Supplementary Table 7 online. Representative genes and positions based on NCBI build 35 of HSAX are shown at top. The
structures of blocks 4 and 4¢ are substantially different. (b) Simulated configuration of the synteny blocks of the predicted common ancestral Y chromosomeof human and chimpanzee. Gray boxes indicate insertion blocks. (c) Syntenic structure of HSAY. P4 to P8 indicate palindromes. The blue shading around
NLGN4Y-STS indicates an inversion. (d) Syntenic structure of PTRY. A large segmental inversion that involves multiple blocks from 4¢-p2 to 1-p1 is shadedin blue.

its human counterpart (280 kb); thus, it was designated as P6+(Figs. 5 and 6). The difference in size is due to an extension that
occurred in chimpanzee P6 after the inversion that includes bothsynteny block 4¢ and part of synteny block 1-p2. Human P6 is likely tobe the ancestral type (Fig. 5).
DISCUSSION
The Y chromosomes of human and chimpanzee show substantial
differences that have accumulated independently during the past 5–6
million years. In order to assess the neutrality of the differences
between the orthologous gene pairs of human and chimpanzee, weestimated the number of synonymous (Ks) and nonsynonymous (Ka)substitutions per nucleotide. Eleven (56%) out of 19 genes showed
Ka/Ks values 41 for at least one splicing variant. VCY, VCY1B,
RPS4Y2 and SRY had Ka/Ks values 43.0 (Table 2). This pattern for
HSAY and PTRY is significantly different from that for HSA21 andPTR22, for which only a small proportion (o10%) of genes showed
Ka/Ks 41 (ref. 10). It should be noted, however, that Ka was

NATURE GENETICS ADVANCE ONLINE PUBLICATION

significantly greater than Ks (at the 0.1% level) for the USP9Y gene
(Supplementary Table 3). There is insufficient genomic sequence data
to examine the difference of the evolutionary patterns of proteincoding genes between the Y chromosomes and the autosomes. Therefore, it is unclear whether the preponderance of nonsynonymous
substitutions for Y chromosome–encoded genes is indicative ofpositive selection. Further comparative genomic studies are necessary
to clarify these points (Supplementary Note).
The extent of genetic variation within P. t. verus also caused a
relatively short time of the most recent common ancestor (TMRCA)
and a small effective population size of male (Nem). When we assume
the species divergence time between humans and chimpanzees to be
6 million years, the mutation rate on the Y chromosome becomes
1.5  10–9 per site per year (0.0178 / (2  6  106)). To estimate the
TMRCA, the divergence rates of the two pairs of chimpanzee
individuals51 were averaged ((0.0422 + 0.0343)/2 ¼ 0.0383). Because
this average divergence can be considered representative for a randomly chosen pair of sequences, the corresponding divergence time is7

ARTICLES

Chimpanzee chromosome Y

P6+

P6+

b P7

P6+

12.80

C2A:AluY C3A:AluY
HC6A:L1PA3

C4A:AluY C4B:AluY

C3B:AluY C2B:AluY
HC6B:L1PA3

C1B:AluY
HC5B:L1PA2

12.90

16.40
AluY
AluY

16.45

16.50

–0.10

14.45

14.50

VCY

14.55
L1PA2
L1PA2

14.60

VCY

–0.05

0.00

0.05

16.55
0.10 Mb

–0.10

–0.05

0.00

0.05

14.65
0.10 Mb

–0.05

0.00

0.05

0.10 Mb

16.70
5.0
16.80

H7B:AluYa5

16.90

H10B:L1PA3

17.00

5.0
Substitution rate (%)

H7A:AluYa5

Substitution rate (%)

P6

H10A:L1PA3

P6

Human chromosome Y

P8P8
CERV CERV
L1PA2 L1PA2

16.50

16.60

4.0
3.0
2.0
1.0
0.0
–0.10

–0.05

0.00

0.05

0.10 Mb

4.0
3.0
2.0
1.0
0.0
–0.10

17.10
HC6C:L1PA3
H8:AluYh9
H9:AluY

–0.50

–0.40

–0.30

–0.20

–0.10

0.00

0.10

0.20

0.30

0.40

17.20
0.50 Mb

–0.40

–0.30

–0.20

–0.10

0.00

0.10

0.20

0.30

0.40

0.50 Mb

5.0
Substitution rate (%)© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

C1A:AluY
HC5A:L1PA2

Human chromosome Y
P7 P7

HC5C:L1PA2

Chimpanzee chromosome Y
Clone gap ~ 15 kb

16.35

12.60

12.70

c P8

Chimpanzee chromosome Y
P7 P7

Human chromosome Y
P8 P8

a

4.0
3.0
2.0
1.0
0.0
–0.50

a half of the TMRCA for many sampled sequences41. Then the
TMRCA becomes 260,000 ± 20,000 years (2  0.000383 / (2  1.5
 10–9)). Because the expected value of nucleotide diversity, p, iscalculated as 2Nemmg, where mg is the mutation rate per site per
generation, we obtained mg ¼ 2.25  10–8 per site per generation(1.5  10–9  15) and estimated Nem as 8,400 ± 760, assuming ageneration time of 15 years. Note that even these small TMRCA and
Nem values are close to those in the extant human Y chromosomes(TMRCA ¼ B40,000 to B140,000 years and Nem ¼ B5,000 toB8,100; see ref. 42 and references therein).
We also compared the genetic variability of the Y chromosome withthat of autosomal data. In the case of PTR22, we obtained diversity
rates of 0.172 ± 0.010% (CHORI-251) and 0.149 ± 0.003% (RP-43)
between the same two chimpanzee individuals51—substantially higher
values than for PTRY. In the case of the Y chromosome, because ofdifferences in the mode of inheritance and in ploidy, the extent of
intraspecies nucleotide divergence is expected to be one-quarter ofthat of autosomes, assuming that the mutation rate is the same for the
Y chromosome and the autosomes, and that the sex ratio is equal to 1.
As mentioned in the previous section, because the mutation rate of the
Y chromosome is likely to be a times higher than that of autosomes,
the ratio of intraspecies divergence of the Y chromosome to that of anautosome should be a/4 and should tend towards 1, as long as a is not
small. However, we observed a ratio of approximately 0.25, which issmaller than this expectation. This suggests two possibilities. First,
natural selection has an important role in reducing intraspecies divergence. Owing to the nonrecombining nature of the8

Figure 6 Comparison of the palindromic structures between PTRY and
HSAY. Shown are dot plot analysis between the corresponding palindromesof PTRY and HSAY (upper plots in each panel) and the nucleotide
substitution rates between the palindrome arms, spacer regions or flanking
regions of the palindromes (lower plots in each panel). In addition,
positions of the repetitive elements found in both palindrome arms areindicated by colored circles. (a) Comparison between P6+ in PTRY and P6
in HSAY. (b) Comparison of P7 between PTRY and HSAY. (c) Comparisonof P8 between PTRY and HSAY. Higher nucleotide substitution rates wereobserved at the boundaries between the palindrome arms and the outsideof the palindrome. Both human and chimpanzee VCY and VCY1B genes
are located on the palindrome arms. The clone gap (approximately 15 kb)
in PTRY P8 is indicated above the PTRY P8 arm.

Y chromosome, both negative and positive selection can clearly reducethe divergence of the entire chromosome, a mechanism known asbackground selection or selective sweep. Second, this may reflect somebehavioral characteristics in chimpanzees, such as reproductive behavior in chimpanzee society or differences in migration rate (orpattern) between males and females. For example, if there is a small
number of dominantly reproducing males, the effective size of themale population is reduced. Large-scale population studies should be
able to address this problem, and we believe that our data and the
HSAY data19 provide additional support for further population studiesof the Y chromosome27,43–45.
The integration of endogenous viral DNAs is an additional insertion event that occurred in the chimpanzee lineage. As the 14
endogenous viral sequences still retain the typical gene arrangementof the retrovirus, LTR-gag-pol-env-LTR, these insertions must haveoccurred relatively recently through the expansion of a particular typeof LTR retrotransposon. Or alternatively, they may be the relics of an
epidemic viral infection. In total, we detected approximately 100
copies of these insertions in the chimpanzee draft sequence (datanot shown), the same as reported previously36. Considering the
proportion of the sequence analyzed in this study, approximately
0.4% of the total genome, extrapolation of the insertion frequency in
PTRY (14 copies) to the entire genome predicts 3,500 copies of these
insertions, which is much higher than the observed value of 100. Thissuggests that the removal of deleterious events from the autosomes
was by recombination or other repair mechanisms or, less likely, that aY-specific insertion mechanism was the cause.

ADVANCE ONLINE PUBLICATION NATURE GENETICS© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

ARTICLES
The simulated structure of the common ancestral Y chromosome
suggests several large-scale insertion and deletion events. In the humanlineage, for example, a 1.4-Mb insertion containing two palindromes(P4 and P5) split synteny block 3 into parts 3-h1 and 3-h2 (Fig. 5c) in
the well-known X-transposed region located near the PAR1-MSY
boundary18–20. The largest insertion (5 Mb) splits synteny block 1
into parts 1-h1 and 1-h2. Analysis of the surrounding regions suggests
it is most likely that the 5-Mb insertion, which contains the centromere, is the result of a translocation. We also identified a relatively
short deletion (approximately 150 kb) in human synteny block 10(10-h0). In contrast, only two insertion blocks, of 0.1 Mb and1.2 Mb, were observed on the common ancestral chromosome(Fig. 5b). Notably, no significant indels were observed in the corresponding regions of PTRY (synteny blocks 12 to 4) except for thesegmentally duplicated parts of synteny blocks 1 and 4 introduced via
a palindromic formation (Fig. 5b,d).
The VCY and VCY1B genes are located at opposite ends of the P8
palindrome in opposing orientations with the promoters on theinside, although in their counterpart on the X chromosome, VCX
does not form a palindromic structure. Although the configuration of
VCY and VCY1B is identical in human and chimpanzee, both of thehuman genes contain a single 30-bp unit encoding a glutamic acid–rich domain, whereas both of the chimpanzee genes contain eight
30-bp repeating units. The chimpanzee genes are unlikely to betranslated into proteins owing to the presence of a stop codon
upstream of the 30-bp repeats.
Future studies need to address the reason for the conservation of
the structure of seemingly inactive chimpanzee VCY genes and otherpalindromic structures. However, we can suggest several possibilities,
such as a gene conversion–like mechanism between the arms of thepalindrome40,46 or a mismatch repair mechanism using two palindrome arms as templates. Comparison of the nucleotide substitution
rates between PTRY and HSAY P6+ (P6), P7 and P8 also supports thisidea (Fig. 6 and Supplementary Note). We identified at least fivehighly conserved ampliconic structures on PTRY. Because of theircomplex nature, we could only partially sequence these regions, but wewere still able to clarify the chimpanzee-specific palindromic structure(CSP1) near the centromere of PTRYq and find evidence for an
intrachromosomal duplication between the arms of the chromosome at regions near the centromere (Supplementary Fig. 6 andSupplementary Note).
There are at least 12 major haplotype groups in the current human
Y chromosome population45. We have previously reported differencesin spermatogenic ability among males with different Y haplotypes.
This introduces the possibility that higher spermatogenic ability could
have acted favorably in the past; that is, Y chromosomes having genes
advantageous to male fitness could increase their frequency in the
population within a relatively short time47,48. The accelerated rate ofevolution of the Y chromosome along with recent changes in the
population size of great apes and changes in human society related toreproductive behavior may impose other effects on the population of
their Y chromosomes.
The Y chromosome has often been regarded as a genetic
wasteland; however, we believe that the structural characteristics
presented in this study provide us with a realistic model ofthe dynamic changes that our genomes have undergone during
the past 5–6 million years, since the separation of human andchimpanzee. Further comparative studies like this one will lead toa better understanding of the mechanisms through which ourmodern-day genomes and chromosomes have evolved from thoseof our ancestors.

NATURE GENETICS ADVANCE ONLINE PUBLICATIONMETHODS
Mapping and sequencing of chimpanzee Y chromosome. Seed clones forconstruction of clone contigs were initially selected using a PCR screening
system with the three-dimensionally arranged PTB1 library4 using existing or
newly designed STS information from the sequence of HSAY1,19,49. Theseclones were then subjected to clone-end or draft sequencing, from which new
chromosome walking primers were designed for further screening and examination of clone overlaps. Several representative clones were also examined
cytogenetically to confirm their localization on the chromosome by FISH
analysis. In addition, we constructed Y chromosome–specific BAC (PTBY) andfosmid (PTFY) libraries for extending clone contigs and gap closing10.
Sequence accuracy was calculated from 5.6 Mb of overlapping clone data.
Alignment of human and chimpanzee sequences. The PTRY sequence was
first screened for matches with the published HSAY sequence19 using the NCBIBLAST program. All the matched pairs were then subjected to a globalalignment process using the LAGAN program50. The alignments were thenrefined by manual inspection. The alignment data is available from the web siteof the RIKEN Genomic Sciences Center.
Gene annotation. We used manually curated HSAY annotations provided by the
HAVANA group of The Wellcome Trust Sanger Institute. Positions of the humangenes were converted to those on PTRY through the sequence alignments(Supplementary Table 2). Finally, all the genes mapped on the corresponding
region of HSAY in the Vertebrate Genome Annotation (VEGA) and NCBI
RefSeq databases were confirmed in the finished sequence except for CD24L4.
Analysis of the species-specific expansion of repetitive elements. We choseyoung Alu and L1 elements for further analysis (Fig. 4) if the indels contained
the entire unit or if divergence was o3% (Supplementary Table 6).
Analysis of synteny blocks. Synteny blocks in the X-degenerate regions of
HSAY and PTRY were surveyed through local alignments obtained fromhomologous regions between HSAX-HSAY and HSAX-PTRY using the
BLASTN program. Regions longer than 30 kb and those that showed similarity
to the region between PAR1 (ref. 20) and the AMELX gene of HSAX (from2.7 Mb to 11.2 Mb) were used to construct the synteny map (Fig. 5). We thenassessed the process of structural changes from HSAX (used as a hypotheticalancestor of the region) to the sequenced region of PTRYq and the corresponding region of HSAY as the most parsimonious series of inversions throughcomputational calculation. After large indels were integrated, a common
ancestral Y chromosome was defined as the branch point of the two pathways
from HSAX to PTRYq (Fig. 5 and Supplementary Fig. 5).
Accession codes. GenBank/DDBJ/EMBL: AY692036, AY692037, BS000531–
BS000572, BS000574–BS000581, BS000583, BS000585, BS000587–BS000682.
See Supplementary Table 1 for a full list of the clone names and accession
numbers. In addition, the following as yet unpublished BACs, listed
in Supplementary Table 5, were generated and deposited in GenBank by
R.K. Wilson (Washington University School of Medicine) and D.C. Page
(Whitehead Institute): AC142320, AC144378, AC145769, AC145782,
AC146011, AC146175, AC146245, AC146268, AC147117, AC147148,
AC147343, AC147657, AC147670 and AC151848.
URLs. Manually annotated HSAY genes, http://vega.sanger.ac.uk/Homo_sapiens/; NCBI, http://www.ncbi.nlm.nih.gov/; NCBI BLAST, http://www.
ncbi.nlm.nih.gov/BLAST/; RIKEN-Genomic Sciences Center, http://stt.gsc.
riken.jp/.
Note: Supplementary information is available on the Nature Genetics website.
ACKNOWLEDGMENTS
We are grateful to all the technical staff of RIKEN Genomic Sciences Center(RIKEN-GSC) and Genome Research Center, Korea Research Institute of
Bioscience and Biotechnology (KRIBB). In addition, we wish to thankY. Nakahori (Tokushima University), T. Matsuzawa (Primate Research Institute,
Kyoto University), T. Ishida (The University of Tokyo), N. Collier (National
Institute of Informatics) for the supply of the human and chimpanzee samples,and discussion. We also thank the Osaka Municipal Tennoji Zoo (Osaka, Japan)

9

ARTICLES© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

for discussions on the subspecies of chimpanzee. We would also like to thank
A. Frankish, E. Hart and J. Harrow from the HAVANA group, the Wellcome Trust
Sanger Institute, for providing annotation of the human Y chromosome. We arealso thankful for D.C. Page (Whitehead Institute), R.K. Wilson (Washington
University School of Medicine) and the Chimpanzee Sequencing and Analysis
Consortium for the availability of the sequences in the public databases. This
work was supported in part by: Special Fund for RIKEN-GSC; Grant-in-Aid for
Scientific Research on Priority Areas ‘‘Genome Science’’ from the Ministry of
Education, Culture, Sports, Science and Technology, Japan; The Ministry of
Science & Technology, Korea, and Special Fund of KRIBB, Korea.
COMPETING INTERESTS STATEMENT
The authors declare that they have no competing financial interests.
Published online at http://www.nature.com/naturegenetics
Reprints and permissions information is available online at http://npg.nature.com/
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Corrigendum: Comparative analysis of chimpanzee and human Y chromosomes unveils complex evolutionary pathway
Y Kuroki, A Toyoda, H Noguchi, T D Taylor, T Itoh, D-S Kim, D-W Kim, S-H Choi, I-C Kim, H H Choi, Y S Kim, Y Satta, N Saitou, T Yamada,
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© 2006 Nature Publishing Group http://www.nature.com/naturegenetics

The following paper, which was published during the revision process of this manuscript, should have appeared in the reference list and shouldhave been cited as below. The authors wish to apologize to the readers and the original data producers for this mistake and inconvenience.
51.
Hughes, J.F. et al. Conservation of Y-linked genes during human evolution revealed by comparative sequencing. Nature 437, 100–
105 (2005).
On page 160, in the first full paragraph in the right-hand column, the first sentence should read, “As the PTRY sequence analyzed in this study
originated from a single male animal, Gon10 (PTB library), we compared intraspecies nucleotide diversity using the sequences in the public database51 (Supplementary Table 5 online).”On page 164, in the first full paragraph in the right-hand column, the third sentence should read, “To estimate the TRMCA, the divergence ratesof the two pairs of chimpanzee individuals51 were averaged ((0.0422 + 0.0343)/2 = 0.0383).”
On page 165, in the first full paragraph in the left-hand column, the second sentence should read, “In the case of PTR22, we obtained diversity
rates of 0.172 ± 0.010% (CHORI-251) and 0.149 ± 0.003% (RP-43) between the same two chimpanzee individuals51—substantially higher values
than for PTRY.”In addition, the following as-yet-unpublished BACs, listed in Supplementary Table 5, were generated and deposited in GenBank by R.K. Wilson(Washington University School of Medicine) and D.C. Page (Whitehead Institute): AC142320, AC144378, AC145769, AC145782, AC146011,
AC146175, AC146245, AC146268, AC147117, AC147148, AC147343, AC147657, AC147670 and AC151848.
Finally, in line 7 of the Acknowledgments, T.-n. Zoo (Osaka, Japan) should have been listed as Osaka Municipal Tennoji Zoo (Osaka, Japan).
The errors have been corrected in the HTML and PDF versions of the article. This correction has been appended to the PDF version.