Mitogenomic meta-analysis identifies two phases of migration in the history of Eastern Eurasian sheep
Full text
A icle Fas T ack
Mi ogenomic Me a-Analysis Iden i ies Two Phases o Mig a ion
in he His o y o Eas e n Eu asian Sheep
Feng-Hua L ,
y,1
Wei-Feng Peng,
y,1,2
Ji Yang,
y,1
Yong-Xin Zhao,
1,2
Wen-Rong Li,
3
Ming-Jun Liu,
3
Yue-Hui Ma,
4
Qian-Jun Zhao,
4
Guang-Li Yang,
1,5
Feng Wang,
6
Jin-Quan Li,
7
Yong-Gang Liu,
8
Zhi-Qiang Shen,
9
Sheng-Guo Zhao,
10
EE Hehua,
11
Neena A. Go khali,
4,12
S. M. Fa had Vahidi,
13
Muhammad Muladno,
14
A i a N. Naq i,
15
Jonna Tabell,
16
Te hi Iso-Tou u,
16
Michael W. B u o d,
17
Juha Kan anen,
16,18
Jian-Lin Han,*
,4,19
Meng-Hua Li*
,1
1
CAS Key Labo a o y o Animal Ecology and Conse a ion Biology, Ins i u e o Zoology, Chinese Academy o Sciences (CAS),
Beijing, China
2
Uni e si y o Chinese Academy o Sciences (UCAS), Beijing, China
3
Animal Bio echnology Resea ch Ins i u e, Xinjiang Academy o Animal Science, U umqi, China
4
CAAS-ILRI Join Labo a o y on Li es ock and Fo age Gene ic Resou ces, Ins i u e o Animal Science, Chinese Academy o
Ag icul u al Sciences (CAAS), Beijing, China
5
College o Li e Sciences, Shangqiu No mal Uni e si y, Shangqiu, China
6
Ins i u e o Sheep and Goa Science, Nanjing Ag icul u al Uni e si y, Nanjing, China
7
College o Animal Science, Inne Mongolia Ag icul u al Uni e si y, Hohho , China
8
College o Animal Science and Technology, Yunnan Ag icul u al Uni e si y, Kunming, China
9
Shandong Binzhou Academy o Animal Science and Ve e ina y Medicine, Binzhou, China
10
College o Animal Science and Technology, Gansu Ag icul u al Uni e si y, Lanzhou, China
11
G ass-Feeding Li es ock Enginee ing Technology Resea ch Cen e , Ningxia Academy o Ag icul u e and Fo es y Sciences,
Yinchuan, China
12
Animal B eeding Di ision, Na ional Animal Science Ins i u e, Nepal Ag icul u e Resea ch Council, Ka hmandu, Nepal
13
Ag icul u al Bio echnology Resea ch Ins i u e o I an-No h B anch (ABRII), Rash , I an
14
Depa men o Animal Technology and P oduc ion Science, Bogo Ag icul u al Uni e si y, Da maga Campus, Bogo , Indonesia
15
Facul y o Li e Sciences, Ka ako am In e na ional Uni e si y, Gilgi , Bal is an, Pakis an
16
G een Technology, Na u al Resou ces Ins i u e Finland (LUKE), Jokioinen, Finland
17
School o Biosciences and Sus ainable Places Resea ch Ins i u e, Ca di Uni e si y, Ca di , Uni ed Kingdom
18
Depa men o Biology, Uni e si y o Eas e n Finland, Kuopio, Finland
19
In e na ional Li es ock Resea ch Ins i u e (ILRI), Nai obi, Kenya
y
These au ho s con ibu ed equally o his wo k.
*Co esponding au ho : E-mail: [email p o ec ed]; m[email p o ec ed].
Associa e edi o : Da id I win
Abs ac
Despi e much a en ion, his o y o sheep (O is a ies) e olu ion, including i s da ing, demog aphic ajec o y and
geog aphic sp ead, emains con o e sial. To add ess hese ques ions, we gene a ed 45 comple e and 875 pa ial
mi ogenomic sequences, and pe o med a me a-analysis o hese and published o ine mi ochond ial DNA se-
quences (n= 3,229) ac oss Eu asia. We in e ed ha O. o ien alis and O. musimon sha e he mos ecen emale
ances o wi h O. a ies a app oxima ely 0.790 Ma (95% CI: 0.637–0.934 Ma) du ing he Middle Pleis ocene, sub-
s an ially p eda ing he domes ica ion e en (~8–11 ka). By econs uc ing his o ical a ia ions in e ec i e
popula ion size, we ound e idence o a apid popula ion inc ease app oxima ely 20–60 ka, immedia ely be o e
he Las Glacial Maximum. Analyses o lineage expansions showed wo sheep mig a o y wa es a app oxima ely
4.5–6.8 ka (lineages A and B: ~6.4–6.8 ka; C: ~4.5 ka) ac oss eas e n Eu asia, which could ha e been in luenced by
p ehis o ic Wes –Eas comme cial ade and delibe a e ma ing o domes ic and wild sheep, espec i ely. A con-
inen -scale examina ion o lineage di e si y and app oxima e Bayesian compu a ion analyses indica ed ha he
Mongolian Pla eau egion was a seconda y cen e o dispe sal, ac ing as a “ anspo a ion hub” in eas e n Eu asia:
Sheep om heMiddleEas e ndomes ica ioncen e we e in e ed o ha e mig a ed h ough he Caucasus and
Cen al Asia, and a i ed in No h and Sou hwes China (lineages A, B, and C) and he Indian subcon inen
ßThe Au ho 2015. Published by Ox o d Uni e si y P ess on behal o he Socie y o Molecula Biology and E olu ion.
This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion Non-Comme cial License
(h p://c ea i ecommons.o g/licenses/by-nc/4.0/), which pe mi s non-comme cial e-use, dis ibu ion, and ep oduc ion in any
medium, p o ided he o iginal wo k is p ope ly ci ed. Fo comme cial e-use, please con ac jou nals.pe mission[email p o ec ed] Open Access
Mol. Biol. E ol. 32(10):2515–2533 doi:10.1093/molbe /ms 139 Ad ance Access publica ion June 16, 2015 2515
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
(lineages B and C) h ough his egion. Ou esul s p o ide new insigh s in o sheep domes ica ion, pa icula ly
wi h espec o o igins and mig a ions o and om eas e n Eu asia.
Key wo ds: wild ances o , domes ica ion, gene low, mi ogenome, O is a ies, me a-analysis, coloniza ion simula ion.
In oduc ion
As one o he i s animals e e domes ica ed, sheep (O is
a ies) ha e played an impo an ole in human socie y and
ha e sp ead almos globally, ollowing human mig a ions
(Colledge e al. 2005;Chessa e al. 2009). Ea ly e idence implied
ha mode n sheep b eeds we e i s domes ica ed om Asian
mou lon (O. o ien alis) in he Fe ile C escen app oxima ely
8–11 housand yea s ago (ka) (Ryde 1984). Following domes-
ica ion, as many as 1,400 sheep b eeds ha e been de eloped
om hei wild ances o s a e long- e m na u al and in ense
a i icial selec ion (Sche 2000). Du ing his p ocess, human
ac i i ies ha e played a signi ican ole in de e mining he
pa e ns o gene low among b eeds and popula ions (e.g.,
Wa mu h e al. 2012). Thus, an examina ion o con inen -
wide gene ic a iabili y among mode n na i e sheep b eeds
can p o ide a comp ehensi e, in-dep h unde s anding o hei
gene ic o igins and dispe sal, as well as insigh in o he impac
o human ac i i ies on sheep h oughou his o y.
In ecen decades, ema kable analy ical ad ances in pale-
on ological and molecula gene ics ha e ans o med ou un-
de s anding o he o igins and egional expansion o domes ic
sheep (Poplin 1979;Hiendlede , Mainz, e al. 1998;Ped osa
e al. 2005;Chessa e al. 2009;Meadows e al. 2007,2011;Kijas
e al. 2009,2012;Demi ci e al. 2013). Mo phological change
and demog aphic analysis implied ha sheep we e likely
b ough unde domes ica ion in a egion ha s e ches
om no he n Zag os o sou heas e n Ana olia, app oxi-
ma ely 10.5–11 ka o pe haps e en ea lie (Pe e s e al.
2005). In addi ion, a ecen in es iga ion on endogenous e-
o i al sequences e ealed a ema kable seconda y popula-
ion expansion o imp o ed domes ic sheep, mos likely ou
o Sou hwes Asia (i.e., he Middle Eas ; Chessa e al. 2009).
Mi ochond ial DNA (m DNA) sequence analyses ha e iden-
i ied a gene al phenomenon o mul iple ma e nal lineages
(i.e., A, B, C, D, and E), some wi h speci ic geog aphic anges,
implying mul iple ma e nal o igins and possibly independen
domes ica ion e en s in sheep (Wood and Phua 1996;
Hiendlede , Mainz, e al. 1998;Guo e al. 2005;Ped osa
e al. 2005;Tapio e al. 2006;Meadows e al. 2007;Singh
e al. 2013).
Es ima es om comple e and/o pa ial m DNA sequences
ha e enabled a ious di e gence ime es ima es be ween do-
mes ic and wild sheep as well as among he i e majo ma-
e nal lineages o O. a ies (e.g., Hiendlede , Mainz, e al. 1998;
Ped osa e al. 2005;Chen e al. 2006;Meadows e al. 2011). In
gene al, he es ima ed di e gence imes among he i e majo
lineages ha e been much ea lie han he domes ica ion
pe iod in e ed om a cheological e idence (Ba -Yose and
Meadow 1995;Zede 2008). Fo example, he di e gence ime
be ween he wo mos common lineages (i.e., A and B) was
es ima ed o be as ea ly as 1.6–1.7 Ma based on cy och ome b
(Cy -b) sequences (Hiendlede , Mainz, e al. 1998). In addi ion,
Ped osa e al. (2005) and Chen e al. (2006) sugges ed he
di e gence ime o lineage C om lineages A and B o be
app oxima ely 0.42–0.76 Ma and app oxima ely 0.45–0.75 Ma
om he analysis o con ol egion and Cy -bsequences, e-
spec i ely. Howe e , a mo e ecen s udy (Meadows e al.
2011) using 12 p o ein-coding genes om comple e mi oge-
nomes implied mo e ecen di e gence be ween he lineages:
Fo example, 0.590 0.17 Ma be ween A and B and
0.26 0.09 Ma be ween C and E.
So a , mos o ine m DNA in es iga ions ha e only o-
cused on one o wo segmen s wi hin Cy -bgene and he
con ol egion (including he hype a iable egion; e.g.,
Ped osa e al. 2005); ne e heless, high le els o ecu en
mu a ions obse ed in he sho segmen wi hin con ol
egion in many mammal species may bias da ing es ima es
(e.g., Achilli e al. 2009,2012; see also he e iews in To oni
e al. 2006;Tabe le e al. 2008). Mo eo e , p e ious sheep
m DNA s udies ha e me ely included b eeds a a egional
(e.g., Ped osa e al. 2005;Chen e al. 2006;Wang e al. 2006;
Meadows e al. 2007)o subcon inen alscale(e.g.,Tapio e al.
2006), whe eas ma e nal lineages o domes ic sheep, pa icu-
la ly o b eeds in Sou hwes , Cen al, Eas and Sou h Asia,
including he Caucasus, I an, Pakis an, Nepal, Indonesia,
Mongolia, China, and India, ha e been la gely excluded
om in eg a ed analyses. In addi ion, he di e gence scena ios
ha e no been ully e alua ed based on comple e mi ogen-
omes ei he , which could ha e p o ided e ined phylogenies
o ma e nal lineages and obus es ima ions o gene ic a i-
abili y and di e gence ime in domes ic animals (see he
e iew in Wang e al. 2014). The e o e, al hough hese ea ly
m DNA s udies ha e p o ided use ul insigh s in o he his o y
o sheep domes ica ion in Eu asia, answe s o some basic
ques ions su ounding he domes ica ion p ocess a e a
om being se led. Fo example, phylogene ic ela ionships
among wild and domes ic sheep (e.g., Hiendlede , Lewalski,
e al. 1998;Meadows e al. 2007), di e gence imes be ween
he majo ma e nal lineages (e.g., Ped osa e al. 2005;Zede
2008;Meadows e al. 2011), demog aphic his o y and popu-
la ion ecoloniza ion (Dobney and La son 2006;Zede 2008),
and o igins o di e en m DNA lineages (Tapio e al. 2006;
Meadows e al. 2007;Demi ci e al. 2013;Singh e al. 2013), as
well as he con inen -wide pa e ns o gene low om he
pos ula ed Middle Eas e n domes ica ion cen e o Cen al,
Eas and Sou h Asia (see, e.g., Tapio e al. 2006,2010;Cai e al.
2007,2011) emain p o isional o unadd essed.
The main objec i e o ou s udy was o be e unde s and
he domes ica ion and expansion o O. a ies ac oss Eu asia
h ough a me a-analysis o comple e and pa ial o ine mi o-
genomic sequences. Mo e speci ically, we aimed o e ine and
challenge exis ing pa adigms on he wild o igin, lineage di e -
gence, demog aphic his o y and popula ion ecoloniza ion o
mode n sheep, pa icula ly he b eeds p esen in eas e n
Eu asia. Fo hese pu poses, we sequenced he comple e
2516
L e al. .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
mi ogenomes o 45 indi iduals (including O. o ien alis,O.
ignei, and 42 na i e b eeds o O. a ies) and he con ol
egion o a o al o 875 animals (including 51 na i e b eeds)
om eas e n Eu asia ( ig. 1 and supplemen a y ables S1 and
S2,Supplemen a y Ma e ial online). Toge he wi h he se-
quences e ie ed om GenBank, we analyzed 85 comple e
mi ogenomes o domes ic sheep including each o he 5
lineages and 10 comple e mi ogenomes o O. o ien alis,O.
musimon,O. ignei,O. ammon,andO. canadensis using phy-
logene ics, molecula -da ing, and demog aphic- econs uc-
ion app oaches. Full con ol egion and Cy -bsequences o
se en ex an wild sheep species (O. o ien alis,O. musimon,O.
ignei,O. ammon,O. canadensis,O. dalli,andO. ni icola)we e
also included in phylogene ic econs uc ions. Fu he mo e,
we ca ied ou a me a-analysis and a simula ion o coloniza-
ion (e.g., app oxima e Bayesian compu a ion, ABC) o
m DNA sequences, including 547 pa ial Cy -band 1,470
pa ial con ol egion sequences published p e iously (sup-
plemen a y ables S2 and S3,Supplemen a y Ma e ial online),
om na i e sheep b eeds ac oss Eu asia. We ied o add ess
hese ques ions and es wo hypo heses on domes ica ion
and mig a ions o sheep dis ibu ed pa icula ly in eas e n
Eu asia. One is he mo e ecen o igin and dispe sal o lineage
C when compa ed wi h hose o he wo widely dis ibu ed
lineages A and B (B u o d 2005;Tapio e al. 2006). Ano he is
ha he a i al o some Indian sheep om he Middle Eas e n
domes ica ion cen e could be h ough he Mongolian
Pla eau egion, whe e a cheological emains showed an
ea ly p esence o domes ic sheep in ancien his o y (e.g.,
Kuo e al. 1999;seealsoYang e al. 2015). Ou esul s could
help esea che s be e unde s and he demog aphic o ces
and human p ac ice associa ed wi h animal domes ica ion
and mig a ion in his o y (e.g., Hodges 1999;La son e al.
2007,2010;La son and Bu ge 2013).
FIG.1. Geog aphic dis ibu ion o he samples in his and ea ly o ine m DNA s udies.
2517
O ine Mi ogenomic Va ia ions ac oss Eas e n Eu asia .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
Resul s
Geog aphic Pa e ns o m DNA Va ia ion
The 45 comple e domes ic (GenBank accession numbe s
KF938317–KF938359) and wild (KF938360–KF938361)
sheep mi ogenomes (supplemen a y able S1,
Supplemen a y Ma e ial online) sequenced in his s udy
showed conside able sequence a iabili y as well as a ia ion
in di e si y among di e en egions (supplemen a y able S4
and ig. S1, Supplemen a y Ma e ial online). Also, we de ec ed
a la ge numbe o a iable si es in he in eg a ed da a o
pa ial Cy -band con ol egion (supplemen a y ables S2
and S3,Supplemen a y Ma e ial online). Full desc ip ion o he
comple e mi ogenome and pa ial m DNA sequence a ia-
ionsisinsupplemen a y in o ma ion S1,Supplemen a y
Ma e ial online.
All con ol egion and Cy -bsequences analyzed in his
s udy can be assigned o he i e p e iously de ined lineages
(supplemen a y ables S2 and S3; see also supplemen a y igs.
S2 and S3,Supplemen a y Ma e ial online). The wo pa ial
m DNA agmen s displayed simila geog aphic pa e ns
( ig. 2Band C). Fo con ol egion sequences, lineages A and
FIG.2.Geog aphic dis ibu ion o he i e majo ma e nal lineages ac oss Eu asia based on sequences ob ained in his s udy and e ie ed om
GenBank. (A) Phylogene ic ee in e ed om pa ial con ol egion sequences (le ) and lineage composi ion o sheep in di e en geog aphic egions a
di e en ime poin s ( igh ) based on ancien specimens (Cai e al. 2007,2011;Demi ci e al. 2013;Niemi e al. 2013); (B) lineage equency dis ibu ion o
pa ial con ol egion sequences; p e iously epo ed lineage equencies in 12 egions (I–XII) a e de ailed in supplemen a y able S17,Supplemen a y
Ma e ial online; (C) lineage equency dis ibu ion o pa ial Cy -bsequences; (D) geog aphic dis ibu ion o a - ailed na i e sheep b eeds ( egions wi h
black lines) and lineage C ( egion colo ed in pu ple). Pie plo s show he p opo ions o he i e dis inc lineages (A–E) o domes ic sheep in he di e en
geog aphic egions ( o he de ails o he geog aphic egions, see supplemen a y ables S5 and S6,Supplemen a y Ma e ial online). In he phylogene ic
ee, diagnos ic mu a ions a e showed on he b anches and a e named acco ding o hei nucleo ide posi ions ela i e o he e e ence sequence
AF010406; amino acid eplacemen s a e unde lined and synonymous eplacemen s a e ma ked in black. Con ol egion mu a ions (15,437–16,616 bp)
a e shown in blue. Inse ions a e indica ed by a “+” a e he posi ion numbe and ollowed by he ype o inse ed nucleo ide(s). Mu a ions wi h p e ix
“” indica e iden ical a iable si es ound in Meadows e al. (2007), which a e used o de ine he i e majo lineages.
2518
L e al. .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
B we e he mos common and mos widely dis ibu ed, wi h a
mean combined equency o app oxima ely 89% ( ig. 2Band
C). Lineage A was ex emely equen (~77%) in he Indian
subcon inen , al hough i s equency was less han 10% in
Eu ope. In con as , lineage B was ound mos ly in Eu ope,
wi h i s highes equency ( 490%) in Sou hwes Eu ope
( ig. 2Band C). Lineage C occu ed mainly in he Middle
Eas , he Caspian Sea egion, No h China, and he
Mongolian Pla eau, wi h a mean equency o app oxima ely
18% ( ig. 2B), whe eas a ew haplo ypes o lineage C we e also
ound in he Ibe ian Peninsula, India, Nepal, and Sou hwes
China. A majo i y o he b eeds ha bo ing lineage C we e a -
ailed (including a - ump; 73.1%), highe han he p opo ion
o a - ailed b eeds ha ing lineage A (50.8%) o B (44.8%)
(supplemen a y ables S5 and S6,Supplemen a y Ma e ial
online). In addi ion, we ound a signi ican ly highe mean
equency o lineage C in a - ailed b eeds han in sho -
ailed b eeds ( a - ailed:
C
=0–0.50, mean
C
= 0.19; sho -
ailed:
C
= 0–0.40, mean
C
= 0.05; wo-sample Kolmogo o –
Smi no es : P<0.01; supplemen a y ig. S4,Supplemen a y
Ma e ial online). O he o al 149 b eeds s udied he e, 66 a e
a - ailed, 78 ha bo lineage C, and 57 a e a - ailed sheep
ca ying lineage C. Compa ed wi h he o e lap expec ed by
chance, he e is a la ge and signi ican excess o b eeds ha
a e a - ailed ha bo ing linages C (lineage C: obse ed n= 57,
expec ed by chance n= 34.65, P<0.001; supplemen a y ig.
S5;Supplemen a y Ma e ial online). Lineages D and E ac-
coun ed o app oxima ely 1% o he o al samples and
we e only ound in he Middle Eas (see ig. 2Band C).
A syn he ic map ac oss Eu asia showed ha he b eeds in
he Mongolian Pla eau egion had he highes gene ic a i-
abili y () o con ol egion in Asia ( ig. 3A;supplemen a y
able S7,Supplemen a y Ma e ial online). Fo lineages A and
B, a ela i ely high le el o nucleo ide di e si y was ound in
he Indian subcon inen ( ig. 3Band C). In addi ion, he syn-
he ic map e ealed he highes le el o lineage C a iabili y in
he b eeds o No h China, e en highe han ha o he
b eedsin heMiddleEas ( ig. 3D), he p esumed domes ica-
ion cen e o mode n sheep (Ryde 1984).
Phylogene ic Rela ionships
Phylogene ic ela ionships in e ed om all he 95 comple e
O is mi ogenomes (supplemen a y able S1,Supplemen a y
Ma e ial online) a e shown in igu e 4.The85comple e
mi ogenomes o O. a ies we e assigned o i e majo lineages
( ig. 4). O is ignei,O. ammon, and O. canadensis clus e ed
in o h ee independen clades sepa a ed om O. a ies,
whe eas O. canadensis showed he la ges di e gence. The
clade o O. musimon and O. o ien alis was closely ela ed o
O. a ies. In he phylogene ic ees buil om he ull con ol
egion, Cy -b, and p o ein gene sequences o he comple e
mi ogenomes, he ou b anches o wild sheep ag eed wi h
he opology in e ed om he comple e mi ogenomes, bu
domes ic sheep sequences o med an un esol ed g oup
a he han he i e majo lineages (supplemen a y igs.
S6–S9,Supplemen a y Ma e ial online). Addi ional phyloge-
ne ic ees ob ained wi h he ull con ol egion and Cy -b
sequences o wild and domes ic sheep (supplemen a y igs.
FIG.3. Syn he ic maps illus a ing geog aphic a ia ion o nucleo ide a iabili y o he o al lineages and lineages A, B, and C. (A) The o al lineages, (B)
lineage A, (C) lineage B, and (D)lineageC.
2519
O ine Mi ogenomic Va ia ions ac oss Eas e n Eu asia .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
S10 and S11 and ables S8 and S9,Supplemen a y Ma e ial
online) showed di e en opologies om ha in e ed om
he comple e mi ogenomes ( ig. 4 and supplemen a y ig. S6,
Supplemen a y Ma e ial online). Speci ically, ins ead o
showing close ela ionships only o lineage B as in e ed
om he comple e mi ogenomes ( ig. 4), he haplo ypes o
O. musimon and O. o ien alis clus e ed wi h lineages A, B, and
Co O. a ies con ol egion sequences (supplemen a y ig. S10,
AF010406
KF938353
EF490452
EF490456
KF938341
KF938346
KF938358
KF977845
HM236176-HM236177
KF302461
KF302462
KF302460
KF302447
KF302448
KF938340
KF938351
KF302452
KF302453
KF977846
EF490451
KF938355-KF938356
KF938350
KF938347
KF938352
KF938348
KF938357
EF490455
KF302450-KF302451
KF302449
KF302454
KF302455
KF302456-KF302457
KF302458
KF302459
KF938354
KF938343
KF938344
EF490453
EF490454
KF938360
HM236184
HM236185
KF938328
KF938329
KF938339
KF938349
KF938359
KF938333
KF938335
KF938325
KF938334
KF938321
KF938324
KF938322
KF938323
KF938319
KF938317
KF938337
KF938326
KF938345
KF977847
KF302440-KF302444
KF302445
KF302446
KF938330
HM236175
KF938332
KF938336
KF938338
KF938342
KF938331
HM236174
HM236180
HM236181
KF938320
KF938318
KF938327
HM236178
HM236179
HM236182
HM236183
HM236186
HM236187
HM236189
KF938361
HM236188
JX101654
JN181255
0.52
(0.346-0.694)
0.69
(0.494-0.887)
0.80
(0.583- 1.018)
0.31
(0.200-0.418)
2.60
2.93
(2.453-3.413)
8.31
(6.182-10.436)
B
A
D
E
C
A’B
AB’D
C’E
ABD’CE
A1
7777
VIVIVIIIII
I
PLEISTOCENE
PLIOCENE
NEOGENE QUATERNARY
I: The la e MIOCENE; II: ZANCLEAN; III: PIACENZIAN; IV: GELASIAN; V: CALABRIAN; VI: IONIAN
1.00
100
1.00
73
1.00
100
1.00
100
1.00
77
1.00
97
A
B
C
D
E
O is o ien alis
O is
O is ammon
musimon
O is ignei
O is canadensis
O
is ammo
n
O
i
s
i
g
i
n
g
g
e
i
O
is
c
a
n
a
d
e
d
d
n
Oi
i
i
n
A2
A1a A1b
B2
B1b
B1
B1a
B1a1
B1a2
B1a3
B1a4
B1a5
B1a6
B1a7
B1a8
B1a9
B1a10
B1a12
B1a11
FIG.4. Phylogeny o domes ic and wild sheep in e ed om a o al o 95 comple e mi ogenomes (supplemen a y able S1,Supplemen a y Ma e ial
online) using BI and ML me hods wi h pos e io p obabili y ( he i s alue) and boo s ap alues ( he second alue) on he nodes, espec i ely.
Di e gence imes o he lineages (Ma) we e es ima ed only based on he 61 comple e mi ogenomes o na i e domes ic sheep b eeds and wild sheep
species (see supplemen a y able S1,Supplemen a y Ma e ial online).
2520
L e al. .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
Supplemen a y Ma e ial online), and hey e en sha ed some
Cy -bhaplo ypes o lineages A, B, C, and E (supplemen a y ig.
S11,Supplemen a y Ma e ial online).
The educed median ne wo k analysis o pa ial con ol
egion sequences showed se e al majo adia ing nodes a a
ew mu a ion s eps wi hin lineages A and B. Di e en con i-
bu ions o b eeds o di e en egions we e e iden , bu none
o he majo nodes consis ed o appa en egion-speci ic hap-
lo ypes (supplemen a y ig. S2,Supplemen a y Ma e ial
online). In addi ion, analysis o molecula a iance and pai -
wise-popula ion F
ST
alues indica ed gene ic di e en ia ion
be ween Eu opean and Asian b eeds, whe eas conside able
ma e nal gene low was ound among he b eeds wi hin Asia
and Eu ope, espec i ely (supplemen a y igs. S12–S13 and
ables S10 and S11,Supplemen a y Ma e ial online).
Selec i e P essu e on Di e en Lineages
The log-likelihood alues (ln L) unde he one-, wo-, h ee-
and ou - a io models we e ln L=18,462.81, 18,454.79,
18,419.46 and 18,413.27, espec i ely ( able 1). The !
a io di e ed be ween he b anches unde he same model
and a ied o he same b anches unde di e en models
( able 1). The likelihood a io es s (LRTs) e ealed ha he
di e ences be ween wo models o all he pai wise
compa isons we e signi ican (P<0.01) and ha he ou -
a io model ( ee- a io model)bes i heda a,which
indica ed di e en ! a ios among he lineages. Mean !
alues o he lineages we e !
A
= 0.0457
,
!
B
= 0.0775,
!
D
= 0.0494, and !
C+E
= 0.0496 (supplemen a y ig. S14,
Supplemen a y Ma e ial online); no e ha hese alues a e
all much lowe han 1. This obse a ion indica es ha he
ma e nal lineages (A, B, D, and C + E) ha e been unde s ong
bu a iable in ensi y o pu i ying selec ion: Pu i ying selec ion
on amino acid changes in lineage B has been sligh ly weake
han ha on he o he lineages. Thus, di e gence ime es i-
ma ion (see below) based on he p o ein-coding genes would
be biased. Ins ead, using he synonymous si es migh be a
be e choice o di e gence ime es ima ion.
Di e gence Times o he Nodes
The es ima ed di e gence imes wi hin he comp ehen-
si e e olu iona y amewo k o he Ce a iodac yla a e
shown in supplemen a y igu e S15,Supplemen a y
Ma e ial online. The O. ignei/O. a ies spli , which is he
calib a ion poin applied o es ima e he di e gence imes
be ween ex an O. a ies lineages, was 2.6 0.9 Ma. Tha
ime is a ea lie han he mos ecen common ances o
(TMRCA) o domes ic sheep (~0.79 Ma; 95% CI: 0.64–
0.93 Ma; able 2), and e en olde han he O. ammon/O.
a ies spli (2.13 0.29 Ma) es ima ed by Meadows e al.
(2011).TheCap a/O is spli was es ima ed o be
14.7 2.1 Ma (supplemen a y ig. S15,Supplemen a y
Ma e ial online), and is much olde han he da e based
on he ungula e ossil eco d (~5.00–7.0 Ma; Luika e al.
2001). Using he calib a ion poin , we ob ained a subs i-
u ion a e o 0.70 10
8
subs i u ions pe nucleo ide/
yea o comple e mi ogenome, 3.12 10
8
subs i u ions
pe nucleo ide/yea o con ol egion, and 0.49 10
8
pe nucleo ide/yea o Cy -bwi hou pa i ions.
The di e gence imes o each node we e mos ly conco -
dan unde global and local clock models when es ima ed
om he comple e mi ogenomes, he synonymous mu a-
ions o he hi d-codon posi ions ( able 2). The ea lies
spli was es ima ed o be app oxima ely 0.73–0.93 Ma o
hedi e genceo CandE omA,B,andD(see henode4
in able 2), whe eas he mos ecen spli was be ween line-
ages C and E a app oxima ely 0.29–0.36 Ma (see he node 1
in able 2), g ea ly p eda ing sheep domes ica ion (~8–11 ka;
Ryde 1984).The ime oTMRCAo he womos common
lineages (A and B) was es ima ed o be app oxima ely 0.50–
0.53 Ma (see node 2 in able 2). Unde he elaxed molecula
clock, we also ob ained simila es ima es o di e gence imes
o he nodes based on di e en da a se s (i.e., comple e
mi ogenomes, synonymous, and hi d-codon posi ions; see
able 2). Howe e , di e gence imes o nodes 2, 3, and 4
es ima ed om synonymous mu a ions by he Bayesian
In e ence (BI) app oach we e signi ican ly (P<0.05) highe
han hose by he global and local maximum likelihood (ML)
Table 1. Numbe o Pa ame e s Fi ed, dN/dSRa ios, Log-Likelihood Sco es, and Thei Di e ences unde Di e en Models.
Model pln LxModels Compa ed 2ln L
A: One x a io x
0
102 18,462.81 x
0
= 0.0563
B: Two x a ios x
B
103 18,454.79 x
B
= 0.0702
x
0
x
0
= 0.0436 A e sus B 16.04**
C: Th ee x a ios x
A
104 18,419.46 x
A
= 0.0447 A e sus C 86.70**
x
B
x
B
= 0.0744 A e sus D 99.08**
x
0
x
0
= 0.0486 B e sus C 70.66**
D: Fou x a ios x
A
105 18,413.27 x
A
= 0.0457 B e sus D 83.04**
x
B
x
B
= 0.0775 C e sus D 12.38**
x
D
x
D
= 0.0494
x
0
x
0
= 0.0496
NOTE.—p, numbe o pa ame e s in he model; ln L, log-likelihood sco e; !, he dN/dS a io o he b anches; !
A
,!
B
,and!
D
a e he dN/dS a ios o b anches lineages A, B, and
D, espec i ely (see supplemen a y ig. S14,Supplemen a y Ma e ial online); !
0
is he backg ound dN/dS a io o he es b anch(es); 2ln L, wice he log-likelihood di e ence o
he models compa ed.
**Ve y signi ican (P<0.01).
2521
O ine Mi ogenomic Va ia ions ac oss Eas e n Eu asia .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
app oaches, espec i ely (supplemen a y ig. S16,
Supplemen a y Ma e ial online).
P ehis o ic Popula ion Expansions
Bayesian skyline plo (BSP) econs uc ions o his o ical po-
pula ion expansions using hecomple emi ogenomes e-
ealed he p o ile o p edomes ic change in Ne o e la ge
ime scales. Based on he es ima ed TMRCA o he lineages
(~0.79 Ma) om comple e mi ogenomes, he o ine lineages
showed a s eep inc ease in Ne a app oxima ely 20–60 ka
(supplemen a y ig. S17,Supplemen a y Ma e ial online). A
p ehis o ic s eep inc ease in Ne was also iden i ied in he
simula ions o he pa ial Cy -band con ol egion sequences
(supplemen a y ig. S18,Supplemen a y Ma e ial online).
Howe e , popula ion g ow h was ound o ha e occu ed
a app oxima ely 50–300 ka, much ea lie han he ime ob-
ained om simula ions o he comple e mi ogenomes (~20–
60 ka; supplemen a y ig. S17,Supplemen a y Ma e ial
online).
Pos domes ic Lineage Expansions
A syn he ic map cons uc ed wi h he use o in e pola ed
1
alues, he eigen alues o he i s mul idimensional scaling
(MDS) plo dimension, allows us o examine he g adien s o
coloniza ion ou o he sheep domes ica ion cen e ha peak
in heMiddleEas ( ig. 5A;supplemen a y able S12,
Supplemen a y Ma e ial online).
1
explains 69.3% o he
o al a ia ion. We obse e a signi ican co ela ion be ween
he
1
eigen alues o Asian popula ions and hei geog aphic
dis ances om he domes ica ion cen e (lineages A, B, and C
o Cen al and Eas Asian popula ions: = 0.201; P<0.05;
lineage A o A abian and Indian popula ions: = 0.547;
P<0.01; see ig. 5Cand D). This sugges s ha he majo
coloniza ion p ocess o he Middle Eas e n sheep o eas e n
Eu asia (including Mongolia, China, and India) was h ough
he Caucasus and Cen al Asia. The in e pola ion map o he
2
eigen alues sugges s ha he second MDS dimension
could ep esen gene ic in luence om he Mongolian
Pla eau egion in China and he Indian subcon inen ( ig.
5B).
2
explains 27.3% o he o al a ia ion. I s anking
shows he Mongolian Pla eau egion a one ex eme, whe eas
he Indian subcon inen a he o he ex eme. This is sup-
po ed by a s ong and signi ican co ela ion obse ed be-
ween geog aphic dis ances om he pu a i e egion o ini ial
coloniza ion (i.e., he Mongolian Pla eau egion) and
2
alues
ac oss eas e n Eu asian popula ions ( = 0.372; P<0.01; ig.
5E). Eigen alues
1
and
2
o all he popula ions a e shown in
supplemen a y able S12,Supplemen a y Ma e ial online.
The s a -like median-joining ne wo ks (supplemen a y ig.
S2,Supplemen a y Ma e ial online) and misma ch dis ibu-
ions (supplemen a y ig. S19,Supplemen a y Ma e ial
online) e ealed gene ic signa u es o pos domes ic demo-
g aphic popula ion expansions in lineages A, B, and C. The
in e ence was co obo a ed by Fs(Fu 1997), Tajima’s D(1989),
and scaled e ec i e popula ion size s a is ics (2Nu;N ep e-
sen s he e ec i e popula ion size and udeno es he mu a-
ion a e). Bo h Fu’s Fs and Tajima’s Ds a is ics showed
Table 2. Di e gence Time Es ima ed by he Sequences o Comple e Mi ogenomes and he P o ein-Coding Genes (synonymous mu a ion and he hi d-codon posi ion) Using ML and BI Me hods.
Me hod Da a Se Model Node Node 1 (T
C/E
)
Ma
Node 2 (T
A/B
)
Ma
Node 3 (T
AB/D
)
Ma
Node 4 (T
ABD/CE
)
Ma
Node 5 (T
O.a ies/O. ignei
)
Ma
T
O.a ies/O.ammon
Ma
T
O.a ies/O.canadensis
Ma
ML Mi ogenome Global Time 0.36 0.51 0.74 0.88 2.60 3.00 7.72
95%(CI) (0.278–0.439) (0.402–0.616) (0.613–0.867) (0.743–1.013) — (2.673–3.323) (6.567–8.883)
Local Time 0.34 0.53 0.78 0.93 2.60 3.06 8.15
95%(CI) (0.276–0.472) (0.397–0.668) (0.600–0.956) (0.721–1.131) — (2.697–3.419) (6.635–9.664)
Synonymous Global Time 0.31 0.52 0.68 0.79 2.60 2.92 8.36
95%(CI) (0.217–0.405) (0.373–0.661) (0.536–0.829) (0.637–0.934) — (2.535–3.312) (6.441–10.286)
Local Time 0.31 0.52 0.69 0.80 2.60 2.93 8.31
95%(CI) (0.200–0.418) (0.346–0.694) (0.494–0.887) (0.583–1.018) — (2.453–3.413) (6.182–10.436)
Thi d codon Global Time 0.29 0.50 0.64 0.73 2.60 2.81 7.47
95%(CI) (0.190–0.390) (0.361–0.639) (0.497–0.783) (0.579–0.881) — (2.418–3.202) (6.157–8.783)
Local Time 0.29 0.50 0.64 0.73 2.60 2.81 7.47
95%(CI) (0.190–0.390) (0.359–0.636) (0.498–0.783) (0.581–0.882) — (2.414–3.200) (6.158–8.786)
BI Mi ogenome Relaxed-molecula clock Median 0.35 0.55 0.85 0.92 2.60 2.68 6.13
95%HPD (0.130–0.641) (0.266–0.913) (0.390–1.413) (0.464–1.498) — (2.462–3.031) (2.464–11.618)
Synonymous Median 0.41 0.61 0.96 1.06 2.60 2.62 5.89
95%HPD (0.147–0.772) (0.291–1.013) (0.478–1.604) (0.541–1.716) — (2.458–3.338) (5.456–11.598)
Thi d codon Median 0.36 0.57 0.87 0.94 2.60 2.62 6.49
95%HPD (0.142–0.656) (0.27–0.912) (0.421–1.428) (0.472–1.496) — (2.461–3.083) (2.478–12.647)
NOTE.—“—,” no a ailable.
2522
L e al. .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
signi ican (P
F
<0.001; P
D
<0.001; able 3)depa u es om
neu ali y in he h ee lineages. Addi ionally, he obse ed
misma ch dis ibu ions o he lineages we e i ed o he
sudden popula ion expansion models wi h e y low alues
o he sum o squa ed de ia ion (SSD 0.005; able 3) s a is ic
and Ha pending’s Raggedness index (Ha pending 1994;
H
= 0.021–0.031; P
R
<0.5; able 3). Fu he mo e, he es i-
ma ed p e- and pos expansion scaled e ec i e popula ion
sizes (2Nu) indica ed an inc ease in he e ec i e popula ion
size o each o he lineages (A: 0.0–77.81; B: 0.04–16.63, and C:
0.00–15.77; able 3). The pos domes ic expansion ime ex-
p essed in wice he numbe o gene a ions mul iplied by
he mu a ion a e (=2 u ) was ound o be 6.443 ka (90%
CI = 4.279–7.569 ka), 6.811 ka (90% CI: 3.502–9.706 ka), and
4.549 ka (90% CI = 2.402–6.652 ka) o lineages A, B, and C,
espec i ely, when assuming an ini ial expansion (i.e., lineage
A in ol ing Eu opean sheep; Tapio e al. 2006) o equal 9 ka
( able 3 and ig. 6). Sepa a e analyses o he ou majo geo-
g aphic a eas ( he Middle Eas , India, Eas Asia, and Eu ope)
esul ed in wide con idence in e als han hose o he com-
bined analysis and showed somewha di e en es ima es o
( able 3). In pa icula , he expansion ime o lineage C in he
Middle Eas (3.910 ka; 90% CI: 2.818–5.120 ka) was mo e
ecen han ha in Eas Asia (4.967 ka; 90% CI: 1.893–7.842
ka), whe eas ela i ely ea lie expansions in he Middle Eas
we e in e ed o lineages A and B ( able 3). Addi ionally, we
ound much la e expansions o lineages A and B in India
(lineage A: 4.033 ka: 90% CI: 1.517–23.100 ka; lineage B:
3.393 ka; 90% CI: 0.961–16.311 ka) han hose in Eas Asia
(lineage A: 5.877 ka; 90% CI: 5.216–6.681 ka; lineage B: 7.008 ka;
90% CI: 3.030–16.348 ka), espec i ely.
ABC analyses based on he con ol egion sequences iden-
i ied an op imal model o each o he i e se s o candida e
coloniza ion models (lineage A i s -s ep, lineage A second-
s ep, lineage B i s -s ep, lineage B second-s ep, and lineage C;
supplemen a y in o ma ion S4,Supplemen a y Ma e ial
online). The op imal models exhibi ed much highe pos e io
p obabili y and nono e lapped 95% CIs as compa ed wi h
o he candida e models ( able 4). These op imal models in-
dica ed ha 1) lineage A i s colonized om he Middle Eas
o he Mongolian Pla eau egion and he Indian subcon inen
sepa a ely, and la e om he Mongolian Pla eau egion o
No h China, and hen o Sou hwes China ( ig. 6); 2) lineage
B i s colonized om he Middle Eas o he Mongolian
Pla eau egion, and hen om he Mongolian Pla eau
egion o No h and Sou hwes China and he Indian
subcon inen sepa a ely ( ig. 6); and 3) Lineage C i s colo-
nized om he Middle Eas o he Mongolian Pla eau egion,
and la e om he Mongolian Pla eau egion o No h China,
and hen o he Indian subcon inen (e.g., Nepal) ( ig. 6).
AA
B
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0 2000 4000 6000 8000
λ1 (dimension 1)
Dis ance (km)
-0.04
-0.02
0.00
0.02
0.04
0.06
0.08
0.10
0 2000 4000 6000
λ1 (dimension 1)
Dis ance (km)
-2.0
-1.0
0.0
1.0
2.0
3.0
4.0
5.0
6.0
0 500 1000 1500 2000 2500 3000
λ2 (dimension 2)
C
D
E
Dis ance (km)
FIG.5. Syn he ic maps illus a ing geog aphic a ia ion o eigen alues () o he i s woMDSdimensions(
1
and
2
) and eg ession o e sus
geog aphic dis ance om he pu a i e o iginal si e o coloniza ion p ocess. (A)syn he icmap o
1
,(B)syn he icmap o
2
,(C) eg ession o
1
e sus
geog aphic dis ances om he domes ica ion cen e o sheep ( ep esen ed by he geog aphic dis ance om he Kilis p o ince o Tu key, whe e ancien
domes ic sheep a e loca ed; Demi ci e al. 2013) o Asian popula ions ( = 0.201; P<0.05); (D) eg ession o
1
(based on lineage A only) e sus
geog aphic dis ances om he domes ica ion cen e o sheep ( ep esen ed by he geog aphic dis ance om he Kilis p o ince o Tu key, whe e ancien
domes ic sheep a e loca ed; Demi ci e al. 2013) o sheep popula ions om he Indian subcon inen ( = 0.547; P<0.01); and (E) eg essiono
2
e sus
geog aphic dis ances om a pu a i e “ anspo a ion hub” o he Mongolian Pla eau egion ( ep esen ed by he geog aphic dis ance om he
no he nmos popula ion [T ansbaikal Finewool] sampled) o eas e n Eu asian (including China, Mongolia, and India) popula ions ( = 0.372; P<0.01).
2523
O ine Mi ogenomic Va ia ions ac oss Eas e n Eu asia .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
he i o he models o he da a by compa ing wice he log-
likelihood di e ence (2ln L) oa
2
dis ibu ion wi h de-
g ees o eedom equal o he di e ence in he numbe o
pa ame e s be ween he wo models (Yang 1998).
Di e gence Time Es ima ion
Phylogene ic ela ionships wi hin he genus O is (see Resul s)
in e ed in p e ious analyses we e used o es ima e he di e -
gence imes be ween he majo O. a ies lineages using PAML
.4.7 (Yang 2007) and BEAST .1.7.5 (D ummond and Rambau
2007). Due o he lack o an exac ossil eco d be ween O is
species o hecalib a ion,weusedacomp ehensi ee olu-
iona y amewo k (see Nomu a e al. 2013;Jiang e al. 2014)
o es ima e he di e gence ime be ween O. a ies and O. ignei. A
phylogene ic ee including 24 species (supplemen a y able S16,
Supplemen a y Ma e ial online) was in e ed based on he 13
m DNA p o ein-coding genes using he GTR + I + G model in
M Bayes .3.2.2 (Ronquis e al. 2011).Thedi e gence imeswe e
es ima ed based on i e ossil calib a ion poin s (18.3–28.5 Ma
be ween Bo inae and Cap inae, 52–58 Ma be ween Ce acea
and hippopo amus, 434.1 Ma be ween baleen and oo hed
whales, 42.8–63.8 Ma be ween Cani o mia and Feli o mia, and
62.3–71.2 Ma be ween Ca ni o a and Pe issodac yla; see
Nomu a e al. 2013;Jiang e al. 2014). We applied he ob-
ained O. a ies/O. ignei di e gence ime (2.6 Ma; see Resul s)
and h ee models o es ima e he di e gence imes be ween
he i e O. a ies m DNA lineages. Global and local clock
models we e implemen ed using he ML in PAML .4.7
(Yang 2007) and he unco ela ed elaxed-clock model
was implemen ed using BEAST .1.7.5 (D ummond and
Rambau 2007).
We only conside ed he 61 comple e mi ogenomes o wild
sheep species and na i e b eeds o domes ic sheep (supple-
men a y able S1;Supplemen a y Ma e ial online) and ap-
plied h ee s a egies in he ML analysis: One conside ed
he comple e mi ogenomes unde he TN93 model, he
second conside ed he synonymous mu a ions unde he
HKY85 model, and he hi d conside ed only he hi d-
codon posi ions unde he HKY85 model. Simila ly,
Bayesian Ma ko chain Mon e Ca lo (MCMC) analysis o mo-
lecula sequences was pe o med by applying he h ee s a-
egies in he p og am BEAST .1.7.5 (D ummond and
Rambau 2007). Pa ame e s o p io dis ibu ions, including
models o nucleo ide subs i u ion and he di e gence ime
be ween O. a ies and O. ignei, we e se he same as in he ML
analyses desc ibed abo e. Th ee independen uns we e pe -
o med wi h 50 million i e a ions. Samples we e d awn e e y
5,000 MCMC s eps, wi h he i s 25% samples disca ded as
bu n-in. The esul s o he h ee independen uns we e com-
bined using he LogCombine p og am (a ailable a h p://
beas .bio.ed.ac.uk/LogCombine , las accessed Oc obe 16,
2014) om BEAST .1.7.5 (D ummond and Rambau 2007).
Con e gence was con i med by e ec i e sampling size (ESS)
g ea e han 200 using he p og am T ace .1.5 (D ummond
and Rambau 2007; a ailable a h p://beas .bio.ed.ac.uk/
T ace , las accessed Decembe 26, 2014).
BI o Popula ion Expansions
Based on he di e gence ime o in e nal nodes es ima ed
abo e and he 51 comple e mi ogenomes o na i e domes ic
sheep b eeds, we econs uc ed he change in N
e
o O. a ies
h ough ime using BSPs (D ummond e al. 2005). The ana-
lyses we e also pe o med on he pa ial Cy -band con ol
egion sequences. We an h ee independen chains in each
analysis using BEAST .1.7.5 (D ummond and Rambau 2007),
wi h 50 million gene a ions (a e disca ding he i s 10% o
sampled gene a ions as bu n-in) and samples d awn e e y
5,000 s eps. We applied he HKY85 and TN93 models
unde elaxed-clock model o comple e mi ogenomes and
pa ial Cy -bsequences, espec i ely. In he analysis o con ol
egion sequences, we se simila pa ame e alues o 200 mil-
lion gene a ions (a e disca ding he i s 10% o sampled
gene a ions as bu n-in) wi h samples d awn e e y 2,000
s eps unde he HKY85 and elaxed-clock models. The com-
bina ion o h ee independen esul s and checks o con e -
gencewe epe o med ollowing hesamep ocedu esas
desc ibed abo e.
Signa u es o popula ion expansions we e examined using
A lequin .3.5 (Exco ie and Lische 2010). Fi s , he obse ed
and expec ed misma ch dis ibu ions o pai wise di e ences
be ween haplo ypes we e compa ed using Tajima’s D(Tajima
1989)andFu’sFs(Fu 1997) es s o neu ali y. Fu he mo e,
we es ima ed he pa ame e s o he sudden popula ion ex-
pansion model (Roge s 1995), and he i o he da a o he
sudden popula ion expansion model was es ed.
Ha pending’s aggedness index (
H
;Ha pending 1994)o he
obse ed misma ch dis ibu ion was also calcula ed. P alues
o he SSDs es o e alua e he i and signi icance o he
pa ame e s (
H
,D, and Fs) we e de e mined wi h 1,000 coa-
lescen simula ions using A lequin .3.5 (Exco ie and Lische
2010). All he pa ial con ol egion sequences we e included
in he calcula ions.
Fu he , o co obo a e ou in e ence ha he Mongolian
Pla eau egion se es as a “ anspo a ion hub” in eas e n
Eu asia (see Resul s), we dis inguished se e al candida e co-
loniza ion scena ios o he h ee main O. a ies lineages (A, B,
and C) using he ABC (Beaumon e al. 2002) p ocedu e in
DIYABC .2.0.4 (Co nue e al.2014). By inco po a ing all he
O. a ies con ol egion sequences o a 292-bp-long hype a-
iable agmen , we es ed six, eigh , and i e coloniza ion
models ega ding po en ial mig a ion ou es om he
Middle Eas e n domes ica ion cen e o di e en egions in
eas e n Eu asia (e.g., he Mongolian Pla eau egion, No h
China, Sou hwes China, and he Indian subcon inen ) o
he lineages A, B, and C, espec i ely (supplemen a y ig.
S25,Supplemen a y Ma e ial online). De ailed in o ma ion
abou he ABC analyses including he candida e coloniza ion
models es ed was p o ided in supplemen a y in o ma ion
S4,Supplemen a y Ma e ial online.
Supplemen a y Ma e ial
Supplemen a y in o ma ion S1–S4, igu es S1–S25,and ables
S1–S19 a ea ailablea Molecula Biology and E olu ion online
(h p://www.mbe.ox o djou nals.o g/).
2530
L e al. .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
Acknowledgmen s
The au ho s hank San-Gang He, Ya-Wei Sun, Nu bi
Ma zano , Mikhail Oze o , Maciek Mu awski, Ta iana
Kisele a,and hela eMi janaCinkulo o helpinsample
collec ion, Anneli Vi a o echnical assis ance, and D
Alessand o Achilli (Uni e si
adiPe ugia,Pe ugia,I aly) o
his commen s on an ea lie e sion o he manusc ip . This
wo k was suppo ed by he 100- alen P og am o Chinese
Academy o Sciences (CAS), he Na ional High Technology
Resea ch and De elopmen P og am o China (i.e., 863
P og am, g an No. 2013AA102506), he B eak h ough
P ojec o S a egic P io i y P og am o he Chinese
Academy o Sciences (g an No. XDB13000000), he g an s
om Na ional Na u al Science Founda ion o China (g an s
Nos. 31272413 and U1303284), and Academy o Finland
(g an s Nos. 250633 and 256077) as well as Chinese
Go e nmen con ibu ion o CAAS-ILRI Join Labo a o y on
Li es ock and Fo age Gene ic Resou ces in Beijing. The pape
con ibu es o he CGIAR Resea ch P og am on Li es ock and
Fish.
Re e ences
Achilli A, Bon iglio S, Oli ie i A, Malus
a A, Pala M, Kashani BH, Pe ego
UA, Ajmone-Ma san P, Lio a L, Semino O, e al. 2009. The mul i-
ace ed o igin o au ine ca le e lec ed by he mi ochond ial
genome. PLoS One 4:e5753.
Achilli A, Oli ie i A, Soa es P, Lancioni H, Kashani BH, Pe ego UA,
Ne gadze SG, Ca ossa V, San agos ino M, Capomaccio S, e al.
2012. Mi ochond ial genomes om mode n ho ses e eal he
majo haplog oups ha unde wen domes ica ion. P oc Na l Acad
Sci U S A. 109:2449–2454.
Al schul SF, Madden TL, Sch€
a e AA, Zhang J, Zhang Z, Mille W,
Lipman DJ. 1997. Gapped BLAST and PSI-BLAST: a new gene a ion
o p o ein da abase sea ch p og ams. Nucleic Acids Res.
25:3389–3402.
Aniwashi J, Jiahan K, Hakaimo u H, Sulaiman Y, Xi S-Y, Du M, Haila i,
Tue senhali, Ayinue . 2007. S udy on hyb idica ion o wild a gali and
Bashibai sheep. Xinjiang Ag ic Sci. 44:702–705 (in Chinese).
Bandel HJ, Fo s e P, R€
ohl A. 1999. Median-joining ne wo ks o in e -
ing in aspeci ic phylogenies. MolBiolE ol.16:37–48.
Ba -Yose O, Meadow R. 1995. The o igins o ag icul u e in he Nea Eas .
In:P iceT,Gebaue A-B,edi o s.Las hun e s, i s a me s.San aFe:
School o Ame ican Resea ch P ess. p. 39–94.
Beaumon MA, Zhang W, Balding DJ. 2002. App oxima e Bayesian com-
pu a ion in popula ion gene ics. Gene ics 162:2025–2035.
Bj€
o ne eld S, Webs e MT, Vil
a C. 2006. Relaxa ion o selec i e con-
s ain on dog mi ochond ial DNA ollowing domes ica ion.
Genome Res. 16:990–994.
B u o d MW. 2005. Molecula app oaches o unde s anding animal
domes ica ion: wha ha e we lea ned so a ? Wo ld Poul y
Science Associa ion, 4 h Eu opean Poul y Gene ics Symposium.
Dub o nik, C oa ia, 6–8 Oc obe , 2005
Cai DW, Han L, Zhang XL, Zhou H, Zhu H. 2007. DNA analysis o
a chaeological sheep emains om China. JA chaeolSci.
34:1347–1355.
CaiDW,TangZW,YuHX,HanL,RenXY,ZhaoXB,ZhuH,ZhouH.
2011. Ea ly his o y o Chinese domes ic sheep indica ed by ancien
DNA analysis o B onze Age indi iduals. JA chaeolSci.38:896–902.
Ca u he s D. 1949. Beyond he Caspian. A na u alis in Cen al Asia.
Edinbu gh: Oli e and Boyd.
Chen FH, Dong GH, Zhang DJ, Liu XY, Jia X, An CB, Ma MM, Xie YW,
Ba on L, Ren XY, e al. 2015. Ag icul u e acili a ed pe manen
human occupa ion o he Tibe an Pla eau a e 3600 B.P. Science
347:248–250.
Chen SY, Duan ZY, Sha T, Xiangyu J, Wu SF, Zhang YP. 2006. O igin,
gene ic di e si y, and popula ion s uc u e o Chinese domes ic
sheep. Gene 376:216–223.
Chen WH. 1990. Index o da a o ag icul u al a chaeology- a m- ools.
Ag ic A chaeol. 1:425–427. (in Chinese)
ChessaB,Pe ei aF,A naudF,Amo imA,GoyacheF,MainlandI,Kao
RR, Pembe on JM, Be aldi D, S ea MJ, e al. 2009. Re ealing he
his o y o sheep domes ica ion using e o i us in eg a ions. Science
324:532–536.
Colledge S, Conolly J, Shennan S. 2005. The e olu ion o Neoli hic a -
ming om SW Asian o igins o NW Eu opean limi s. Eu J A chaeol.
8:137–156.
Co nue J-M, Pudlo P, Veyssie J, Dehne-Ga cia A, Gau ie M,
LebloisR,Ma inJ-M,Es oupA.2014.DIYABC 2.0:aso wa e
o make app oxima e Bayesian compu a ion in e ences
abou popula ion his o y using single nucleo ide polymo -
phism, DNA sequence and mic osa elli e da a. Bioin o ma ics
30:1187–1189.
C andall KA, Kelsey CR, Imamichi H, Lane HC, Salzman NP. 1999. Pa allel
e olu ion o d ug esis ance in HIV: ailu e o nonsynonymous/sy-
nonymous subs i u ion a e a io o de ec selec ion. Mol Biol E ol.
16:372–382.
Da iba D, Taboada GL, Doallo R, Posada D. 2012. jModelTes 2:
mo e models, new heu is ics and pa allel compu ing. Na
Me hods. 9:772.
Demi ci S, Koban Bas¸ anla E, Da
g as¸ND,Pis¸kin E, Engin A, €
Oze F,
Y€
unc€
uE,Do
gan S¸A, Togan _
I. 2013. Mi ochond ial DNA di e si y o
mode n, ancien and wild sheep (O is gmelinii ana olica) om
Tu key: new insigh s on he e olu iona y his o y o sheep. PLoS
One 8:e81952.
Dobney K, La son G. 2006. Gene ics and animal domes ica ion: new
windows on an elusi e p ocess. J Zool. 269:261–271.
D ummond AJ, Rambau A. 2007. BEAST: Bayesian e olu iona y analysis
by sampling ees. BMC E ol Biol. 7:214.
D ummond AJ, Rambau A, Shapi o B, Pybus OG. 2005. Bayesian coa-
lescen in e ence o pas popula ion dynamics om molecula se-
quences. MolBiolE ol.22:1185–1192.
Exco ie L, Lische HEL. 2010. A lequin sui e e 3.5: a new se ies o
p og ams o pe o m popula ion gene ics analyses unde Linux and
Windows. MolEcolResou .10:564–567.
Felsens ein J. 1985. Con idence limi s on phylogenies: an app oach using
he boo s ap. E olu ion 39:783–791.
Fu Y-X. 1997. S a is ical es s o neu ali y o mu a ions agains popula-
ion g ow h, hi chhiking and backg ound selec ion. Gene ics
147:915–925.
Gau i FN. 2013. Indo-Saudi ade ela ion. A abian Jou nal o Business
and Managemen Re iew (Nige ian Chap e ) 1(2):45–57.
Goldman N, Yang Z. 1994. A codon-based model o nucleo ide
subs i u ion o p o ein-coding DNA sequences. MolBiolE ol.
11:725–736.
G an WS, Liu M, Gao T, Yanagimo o T. 2012. Limi s o Bayesian skyline
plo analysis o m DNA sequences o in e his o ical demog aphies
in Paci ic he ing (and o he species). Mol Phylogene E ol.
65:203–212.
Guindon S, Gascuel O. 2003. A simple, as , and accu a e algo i hm o
es ima e la ge phylogenies by maximum likelihood. Sys Biol.
52:696–704.
Guo J, Du LX, Ma YH, Guan WJ, Li HB, Zhao QJ, Li X, Rao SQ. 2005. A
no el ma e nal lineage e ealed in sheep (O is a ies). Anim Gene .
36:331–336.
Hano e O, B adley DG, Ochieng JW, Ve jee Y, Hill EW, Rege JEO. 2002.
A ican pas o alism: gene ic imp in s o o igins and mig a ions.
Science 296:336–339.
Ha pending H. 1994. Signa u e o ancien popula ion g ow h in a low-
esolu ion mi ochond ial DNA misma ch dis ibu ion. Hum Biol.
66:591–600.
Hasegawa M, Kishino H, Yano T-A. 1985. Da ing o he human-ape
spli ing by a molecula clock o mi ochond ial DNA. J Mol E ol.
22:160–174.
2531
O ine Mi ogenomic Va ia ions ac oss Eas e n Eu asia .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
Helle R, Chikhi L, Siegismund HR. 2013. The con ounding e ec o
popula ion s uc u e on Bayesian skyline plo in e ences o demo-
g aphic his o y. PLoS One 8:e62992.
Hiendlede S, Lewalski H, Wassmu h R, Janke A. 1998. The comple e
mi ochond ial DNA sequence o he domes ic sheep (O is a ies)
and compa ison wi h he o he majo o ine haplo ype. J Mol E ol.
47:441–448.
Hiendlede S, Mainz K, Plan e Y, Lewalski H. 1998. Analysis o mi ochon-
d ial DNA indica es ha domes ic sheep a e de i ed om wo di -
e en ances al ma e nal sou ces: no e idence o con ibu ions
om u ial and a gali sheep. J He ed. 89:113–120.
Ho SYW. 2014. The changing ace o he molecula e olu iona y clock.
T ends Ecol E ol. 29:496–503.
Ho SYW, Duch^
ene S. 2014. Molecula -clock me hods o es ima ing
e olu iona y a es and imescales. Mol Ecol. 23:5947–5965.
Ho SYW, Lan ea R, B omham L, Phillips MJ, Soub ie J, Rod igo AG,
Coope A. 2011. Time-dependen a es o molecula e olu ion. Mol
Ecol. 20:3087–3101.
Ho SYW, Shapi o B. 2011. Skyline-plo me hods o es ima ing demo-
g aphic his o y om nucleo ide sequences. Mol Ecol Resou .
11:423–434.
Hodges J. 1999. Animals and alues in socie y. Li es Res Ru al De .
11:1–6.
Hun HV, Vande Linden M, Liu X, Mo uzai e-Ma uze iciu e G, Colledge
S, Jones MK. 2008. Mille s ac oss Eu asia: ch onology and con ex o
ea ly eco ds o he gene a Panicum and Se a ia om a chaeological
si es in he Old Wo ld. Veg His A chaeobo . 17:5–18.
Jiang Y, Xie M, Chen W, Talbo R, Maddox JF, Fa au T, Wu C, Muzny
DM, Li Y, Zhang W, e al. 2014. The sheep genome illumina es
biology o he umen and lipid me abolism. Science 344:1168–1173.
Jones MK, Liu X. 2009. O igins o ag icul u e in Eas Asia. Science
324:730–731.
Joos S, Bonin A, B u o d MW, Desp es L, Cono d C, E ha d G, Tabe le
P. 2007. A spa ial analysis me hod (SAM) o de ec candida e loci o
selec ion: owa ds a landscape genomics app oach o adap a ion.
Mol Ecol. 16:3955–3969.
Kijas JW, Lens a JA, Hayes B, Boi a d S, Ne o LRP, San C is obal M,
Se in B, McCulloch R, Whan V, Gie zen K, e al. 2012. Genome-
wide analysis o he wo ld’s sheep b eeds e eals high le els o his-
o ic mix u e and s ong ecen selec ion. PLoS Biol. 10:e1001258.
Kijas JW, Townley D, Dal ymple BP, Hea on MP, Maddox JF, McG a h A,
Wilson P, Inge soll RG, McCulloch R, McWilliam S, e al. 2009. A
genome wide su ey o SNP a ia ion e eals he gene ic s uc u e o
sheep b eeds. PLoS One 4:e4668.
Kuma S. 2005. Molecula clocks: ou decades o e olu ion. Na Re
Gene . 6:654–662.
Kuo F, Needham J, Chh^
eng CT. 1999. The his o y o zoology in China.
Beijing (China): Science P ess. (in Chinese)
Lancioni H, Di Lo enzo P, Ceccobelli S, Pe ego UA, Miglio A, Landi V,
An ognoni MT, Sa i FM, Lasagna E, Achilli A. 2013. Phylogene ic
ela ionships o h ee I alian Me ino-de i ed sheep b eeds e alua ed
h ough a comple e mi ogenome analysis. PLoS One 8:e73712.
La kin MA, Blackshields G, B own NP, Chenna R, McGe igan PA,
McWilliam H, Valen in F, Wallace IM, Wilm A, Lopez R, e al.
2007. Clus al W and Clus al X e sion 2.0. Bioin o ma ics
23:2947–2948.
La son G, Alba ella U, Dobney K, Rowley-Conwy P, Schible J, T esse A,
Vigne J-D, Edwa ds CJ, Schlumbaum A, Dinu A, e al. 2007. Ancien
DNA, pig domes ica ion, and he sp ead o he Neoli hic in o
Eu ope. P oc Na l Acad Sci U S A. 104:15276–15281.
La son G, Bu ge J. 2013. A popula ion gene ics iew o animal dome-
s ica ion. T ends Gene . 29:197–205.
La son G, Liu R, Zhao X, Yuan J, Fulle D, Ba on L, Dobney K, Fan Q, Gu
Z, Liu X-H, e al. 2010. Pa e ns o Eas Asian pig domes ica ion,
mig a ion, and u no e e ealed by mode n and ancien DNA. P oc
Na l Acad Sci U S A. 107:7686–7691.
Lippold S, Ma zke NJ, Reissmann M, Ho ei e M. 2011. Whole mi o-
chond ial genome sequencing o domes ic ho ses e eals
inco po a ion o ex ensi e wild ho se di e si y du ing domes ica-
ion. BMC E ol Biol. 11:328.
Lu H, Zhang J, Liu K-B, Wu N, Li Y, Zhou K, Ye M, Zhang T, Zhang H,
Yang X, e al. 2009. Ea lies domes ica ion o common mille
(Panicum miliaceum) in Eas Asia ex ended o 10,000 yea s ago.
P oc Na l Acad Sci U S A. 106:7367–7372.
Luika G, Gielly L, Exco ie L, Vigne J-D, Bou e J, Tabe le P. 2001.
Mul iple ma e nal o igins and weak phylogeog aphic s uc u e in
domes ic goa s. P oc Na l Acad Sci U S A. 98:5927–5932.
Luo Y-Z, Cheng S-R, Lkhag a B, Badamdo j D, Hano e O, Han J-L. 2005.
S udy on o igin and gene ic di e si y o Mongolian and Chinese
sheep. Ac a Gene Sin. 32:1256–1265. (in Chinese)
L F-H, Agha S, Kan anen J, Colli L, S ucki S, Kijas JW, Joos S, Li M-H,
Ma san PA. 2014. Adap a ions o clima e-media ed selec i e p es-
su esinsheep.Mol Biol E ol. 31:3324–3343.
Meadows JR, Cemal I, Ka aca O, Goo wine E, Kijas JW. 2007. Fi e o ine
mi ochond ial lineages iden i ied om sheep b eeds o he Nea
Eas . Gene ics 175:1371–1379.
Meadows JRS, Hiendlede S, Kijas JW. 2011. Haplog oup ela ionships
be ween domes ic and wild sheep esol ed using a mi ogenome
panel. He edi y 106:700–706.
Muigai AT, Hano e O. 2013. The o igin o A ican sheep: a chaeological
and gene ic pe spec i es. A A chaeol Re . 30:39–50.
Nade i S, Rezaei H-R, Pompanon F, Blum MGB, Neg ini R, Naghash H-R,
Balkız €
O, Mashkou M, Gaggio i OE, Ajmone-Ma san P, e al. 2008.
The goa domes ica ion p ocess in e ed om la ge-scale mi ochon-
d ial DNA analysis o wild and domes ic indi iduals. P oc Na l Acad
Sci U S A. 105:17659–17664.
Niemi M, Bl€
aue A, Iso-Tou u T, Nys €
om V, Ha jula J, Taa i sainen J-P,
S o a
˚J, Lid
en K, Kan anen J. 2013. Mi ochond ial DNA and Y-ch o-
mosomal di e si y in ancien popula ions o domes ic sheep (O is
a ies) in Finland: compa ison wi h con empo a y sheep b eeds.
Gene Sel E ol. 45:2.
Nomu a K, Yonezawa T, Mano S, Kawakami S, Shedlock AM, Hasegawa
M, Amano T. 2013. Domes ica ion p ocess o he goa e ealed by
an analysis o he nea ly comple e mi ochond ial p o ein-encoding
genes. PLoS One 8:e67775.
Pe H. 1959. G. H. Luce and Pe Maung Tin (ed.): Insc ip ions o Bu ma.
Po olio IV. Down o 702 B.E. (1340 A.D.).—Po olio V. 703–726
B.E. (1341–1364 A.D.). (Uni e si y o Rangoon O ien al S udies
Publica ion No. 5, No. 6.) 63 pp., pla es 346–462; 38 pp., pla es
463–609. Ox o d: Uni e si y P ess, 1956. Bull Sch O ien A S ud.
22:177.
Ped osa S, Uzun M, A anz JJ, Gu ie ez-Gil B, San P imi i o F, Bayon Y.
2005. E idence o h ee ma e nal lineages in Nea Eas e n sheep
suppo ing mul iple domes ica ion e en s. P oc R Soc Lond B Biol
Sci. 272:2211–2217.
Peng M-S, Zhang Y-P. 2011. In e ing he popula ion expansions in
peoplingo Japan.PLoS One 6:e21509.
Pe ei aL,Sil aNM,F anco-Dua eR,Fe nandesV,Pe ei aJB,Cos aMD,
Ma ins H, Soa es P, Beha DM, Richa ds MB, e al. 2010. Popula ion
expansion in he No h A ican La e Pleis ocene signalled by mi o-
chond ial DNA haplog oup U6. BMC E ol Biol. 10:390.
Pe e s J, on den D iesch A, Helme D. 2005. The uppe Euph a es-Tig is
basin: c adle o ag o-pas o alism. In: Vigne JD, Pe e s J, Helme D,
edi o s. The i s s eps o animal domes ica ion. Ox o d: Oxbow. pp.
96–124.
Pick ell JK, P i cha d JK. 2012. In e ence o popula ion spli s and mix u es
om genome-wide allele equency da a. PLoS Gene . 8:e1002967.
Poplin F. 1979. O igine du mou lon de Co se dans une nou elle pe -
spec i e pal
eon ologique: pa ma onnage. Ann G
en
e S
el Anim.
11:133–134.
Posada D. 2008. jModelTes : phylogene ic model a e aging. Mol Biol
E ol. 25:1253–1256.
R Co e Team. 2014. R: a language and en i onmen o s a is ical com-
pu ing. Vienna (Aus ia): R Founda ion o S a is ical Compu ing.
Reynolds J, Wei BS, Cocke ham CC. 1983. Es ima ion o he co-ances y
coe icien —basis o a sho - e m gene ic-dis ance. Gene ics
105:767–779.
2532
L e al. .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om
Rezaei HR, Nade i S, Chin auan-Ma quie IC, Tabe le P, Vi k AT,
Naghash HR, Rioux D, Kaboli M, Pompanon F. 2010. E olu ion
and axonomy o he wild species o he genus O is (Mammalia,
A iodac yla, Bo idae). Mol Phylogene E ol. 54:315–326.
Roge s AR. 1995. Gene ic e idence o a Pleis ocene popula ion explo-
sion. E olu ion 49:608–615.
Ronquis F, Huelsenbeck J, Teslenko M. 2011. D a M Bayes e sion 3.2
Manual: u o ials and model summa ies. A ailable om:
h p://m bayes.sou ce o ge.ne /.
Rozas J, S
anchez-DelBa io JC, Messegue X, Rozas R. 2003. DnaSP, DNA
polymo phism analyses by he coalescen and o he me hods.
Bioin o ma ics 19:2496–2497.
Ryde ML. 1983. Sheep and man. London: Duckwo h.
Ryde ML. 1984. Sheep. In: Mason IL, edi o . E olu ion o domes ica ed
animals. London/New Yo k: Longman. pp. 63–85.
Samb ook J, Russell DW. 2001. Molecula cloning: a labo a o y manual.
3 d ed. New Yo k: Cold Sp ing Ha bo Labo a o y P ess.
Sche BD, edi o . 2000. Wo ld wa ch lis o domes ic animal di e si y.
In: Food and Ag icul u e O ganiza ion o he Uni ed Na ions. Rome:
Food and Ag icul u e O ganiza ion o he Uni ed Na ions. p. 58.
Shaha R. 1970. Nepal, Tibe and China. JNepalCouncilWo ldA .
3:13–82.
Shi N-N, Fan L, Yao Y-G, Peng M-S, Zhang Y-P. 2014. Mi ochond ial
genomes o domes ic animals need sc u iny. Mol Ecol.
23:5393–5397.
Singh S, Kuma S J , Kol e AP, Kuma S. 2013. Ex ensi e a ia ion and
sub-s uc u ing in lineage A m DNA in Indian sheep: gene ic e i-
dence o domes ica ion o sheep in India. PLoS One 8:e77858.
Tabe le P, Valen ini A, Rezaei HR, Nade i S, Pompanon F, Neg ini R,
Ajmone-Ma san P. 2008. A e ca le, sheep, and goa s endange ed
species? Mol Ecol 17:275–284.
Tajima F. 1989. S a is ical me hod o es ing he neu al mu a ion hy-
po hesis by DNA polymo phism. Gene ics 123:585–595.
Tamu a K, Nei M. 1993. Es ima ion o he numbe o nucleo ide sub-
s i u ions in he con ol egion o mi ochond ial DNA in humans
and chimpanzees. MolBiolE ol.10:512–526.
Tamu a K, Pe e son D, Pe e son N, S eche G, Nei M, Kuma S. 2011.
MEGA5: molecula e olu iona y gene ics analysis using maximum
likelihood, e olu iona y dis ance, and maximum pa simony me-
hods. MolBiolE ol.28:2731–2739.
TapioM,Ma zano N,Oze o M,Cinkulo M,Gonza enkoG,Kiselyo a
T, Mu awski M, Viinalass H, Kan anen J. 2006. Sheep mi ochond ial
DNA a ia ion in Eu opean, Caucasian, and Cen al Asian a eas. Mol
Biol E ol. 23:1776–1783.
TapioM,Oze o M,TapioI,To oMA,Ma zano N,Cinkulo M,
Goncha enko G, Kiselyo a T, Mu awski M, Kan anen J. 2010.
Mic osa elli e-based gene ic di e si y and popula ion s uc u e o
domes ic sheep in no he n Eu asia. BMC Gene . 11:76.
To oni A, Achilli A, Macaulay V, Richa ds M, Bandel H-J. 2006. Ha es ing
he ui o he human m DNA ee. T ends Gene . 22:339–345.
Wang G-D, Xie H-B, Peng M-S, I win D, Zhang Y-P. 2014. Domes ica ion
genomics: e idence om animals. Annu Re Anim Biosci. 2:65–84.
Wang X, Ma Y-H, Chen H. 2006. Analysis o he gene ic di e si y and he
phylogene ic e olu ion o Chinese sheep based on Cy b gene se-
quences. Ac a Gene Sin. 33:1081–1086.
WangZ,YonezawaT,LiuB,MaT,ShenX,SuJ,GuoS,HasegawaM,Liu
J. 2011. Domes ica ion elaxed selec i e cons ain s on he yak mi o-
chod ial genomes. Mol Biol E ol. 28:1553–1556.
Wa mu hV,E ikssonA,Bowe MA,Ba ke G,Ba e E,HanksBK,LiS,
Lomi ash ili D, Ochi -Go yae a M, Sizono GV, e al. 2012.
Recons uc ing he o igin and sp ead o ho se domes ica ion in
he Eu asian s eppe. P oc Na l Acad Sci U S A. 109:8202–8206.
Wood NJ, Phua SH. 1996. Va ia ion in he con ol egion sequence o he
sheep mi ochond ial genome. Anim Gene . 27:25–33.
WuGS,YaoYG,QuKX,DingZL,LiH,PalanichamyMG,DuanZY,LiN,
Chen YS, Zhang YP. 2007. Popula ion phylogenomic analysis o mi-
ochond ial DNA in wild boa s and domes ic pigs e ealed mul iple
domes ica ion e en s in Eas Asia. Genome Biol. 8:R245.
Xiang H, Gao J, Yu B, Zhou H, Cai D, Zhang Y, Chen X, Wang X, Ho ei e
M, Zhao X. 2014. Ea ly Holocene chicken domes ica ion in no he n
China. P oc Na l Acad Sci U S A. 111:17564–17569.
Yang X, Scude i LA, Wang X, Scude i LJ, Zhang D, Li H, Fo man S, Xu
Q, Wang R, Huang W, e al. 2015. G oundwa e sapping as he
cause o i e e sible dese i ica ion o Hunshandake Sandy Lands,
Inne Mongolia, no he n China. P oc Na l Acad Sci U S A.
112:702–706.
Yang X, Wan Z, Pe y L, Lu H, Wang Q, Zhao C, Li J, Xie F, Yu J, Cui T,
e al. 2012. Ea ly mille use in no he n China. P oc Na l Acad Sci U S
A. 109:3726–3730.
Yang Z. 1998. Likelihood a io es s o de ec ing posi i e selec ion and
applica ion o p ima e lysozyme e olu ion. Mol Biol E ol.
15:568–573.
Yang Z. 2007. PAML 4: phylogene ic analysis by maximum likelihood.
MolBiolE ol.24:1586–1591.
Yao Y-G, Salas A, Logan I, Bandel H-J. 2009. m DNA da a mining in
GenBank needs su eying. Am J Hum Gene . 85:929–933.
Yi H. 2004. B onze oads: a in oduc ion o a chaic cul u al exchange in
Eu asia. In: Depa men o Cul u al He i age and Museum S udies,
edi o . An iqui ies o Eas e n Asia. Beijing (China): Cul u al Relics
P ess. (in Chinese)
Zede MA. 2008. Domes ica ion and ea ly ag icul u e in he
Medi e anean Basin: o igins, di usion, and impac . P oc Na l
Acad Sci U S A. 105:11597–11604.
Zede MA, Emshwille E, Smi h BD, B adley DG. 2006. Documen ing
domes ica ion: he in e sec ion o gene ics and a chaeology. T ends
Gene . 22:139–155.
Zhang H, Paijmans JLA, Chang F, Wu X, Chen G, Lei C, Yang X, Wei Z,
B adley DG, O lando L, e al. 2013. Mo phological and gene ic
e idence o ea ly Holocene ca le managemen in no heas e n
China. Na Commun. 4:2755.
2533
O ine Mi ogenomic Va ia ions ac oss Eas e n Eu asia .doi:10.1093/molbe /ms 139 MBE
a Na u al Resou ces Ins i u e Finland (Luke) on Oc obe 6, 2016h p://mbe.ox o djou nals.o g/Downloaded om