全基因组分析揭示猕猴属物种间复杂的渐渗基因流

Yang Song; Cong Jiang; Kun-Hua Li; Jing Li; Hong Qiu; Megan Price; Zhen-Xin Fan; Jing Li

doi:10.24272/j.issn.2095-8137.2021.038

全基因组分析揭示猕猴属物种间复杂的渐渗基因流

doi: 10.24272/j.issn.2095-8137.2021.038

宋飏¹,
江聪¹,
李坤华¹,
李晶²,
邱洪¹,
PriceMegan¹,
范振鑫^{1, 3},
李静^{1, 3, ,}

1.
四川大学生命科学学院，生物资源与生态环境教育部重点实验室，四川成都 610064，中国
2.
四川农业大学动物科技学院动物遗传育种研究所，四川成都 611130，中国
3.
四川大学生命科学学院四川省濒危野生动物保护生物学重点实验室，四川成都 610064，中国

计量
- 文章访问数: 1535
- HTML全文浏览量: 699
- PDF下载量: 294
- 被引次数: 0
出版历程
- 收稿日期: 2021-04-19
- 录用日期: 2021-05-20
- 网络出版日期: 2021-06-09
- 刊出日期: 2021-07-18

Genome-wide analysis reveals signatures of complex introgressive gene flow in macaques (genus Macaca)

Yang Song¹,
Cong Jiang¹,
Kun-Hua Li¹,
Jing Li²,
Hong Qiu¹,
Megan Price¹,
Zhen-Xin Fan^{1, 3},
Jing Li^{1, 3
, ,}

1.
Key Laboratory of Bio-resources and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, China
2.
Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
3.
Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, China

Funds: This work was supported by the National Natural Science Foundation of China (31530068, 31770415) and Fundamental Research Funds for the Central Universities (SCU2021D006)

More Information

Corresponding author: E-mail: ljtjf@126.com

摘要

摘要: 猕猴属物种分化时间较短（约500万年），经历了快速的适应辐射，是物种形成和渐渗基因流研究的理想模型。为了更全面、深入的阐释猕猴属进化过程中的种间基因流，我们对4个猕猴（2个红面猴和2个藏酋猴）进行了全基因组重测序，并结合已报道的猕猴属全基因组数据，我们共分析了14个猕猴个体基因组，覆盖了亚洲猕猴的所有种组。研究结果表明猕猴属中存在着广泛的种间基因流信号，最强的信号出现在fascicularis和silenus种组之间。其中尤其是食蟹猴与南豚尾猴之间的基因流信号最为显著，结合多种基因组分析方法，食蟹猴与与南豚尾猴之间可能存在双向的基因流；且二者因种间基因流而共享的基因组片段占基因组的6.19%。同时也检测到一些岛屿物种（如苏拉威西猕猴和日本猴）与其他猕猴间存在基因流，这可能在很大程度上归因于近缘物种间基因组的相似性或祖先谱系间的杂交事件。此外，我们也发现同一物种（红面猴、恒河猴、食蟹猴、南豚尾猴和藏酋猴）的不同种群个体间存在不一致的基因流信号，表明这些基因流发生在不同的种群分化之后。种群历史动态分析显示所有的亚洲猕猴在500万年前都经历了一次瓶颈，此后，不同物种表现出了不同的种群历史动态，表明猕猴属在进化过程中经历了复杂的环境与气候变化。综上，该研究从全基因组的角度揭示了亚洲猕猴进化过程中复杂的种间基因流。
- 猕猴属 /
- 全基因组 /
- 渐渗 /
- 基因流 /
- 种群历史动态
Abstract: The genus Macaca serves as an ideal research model for speciation and introgressive gene flow due to its short period of diversification (about five million years ago) and rapid radiation of constituent species. To understand evolutionary gene flow in macaques, we sequenced four whole genomes (two M. arctoides and two M. thibetana) and combined them with publicly available macaque genome data for genome-wide analyses. We analyzed 14 individuals from nine Macaca species covering all Asian macaque species groups and detected extensive gene flow signals, with the strongest signals between the fascicularis and silenus species groups. Notably, we detected bidirectional gene flow between M. fascicularis and M. nemestrina. The estimated proportion of the genome inherited via gene flow between the two species was 6.19%. However, the introgression signals found among studied island species, such as Sulawesi macaques and M. fuscata, and other species were largely attributed to the genomic similarity of closely related species or ancestral introgression. Furthermore, gene flow signals varied in individuals of the same species (M. arctoides, M. fascicularis, M. mulatta, M. nemestrina and M. thibetana), suggesting very recent gene flow after the populations split. Pairwise sequentially Markovian coalescence (PSMC) analysis showed all macaques experienced a bottleneck five million years ago, after which different species exhibited different fluctuations in demographic history trajectories, implying they have experienced complicated environmental variation and climate change. These results should help improve our understanding of the complicated evolutionary history of macaques, particularly introgressive gene flow.
- Macaca /
- Whole genome /
- Introgression /
- Gene flow /
- Demographic history

HTML全文

Figure 1. Local evolutionary history of macaques at individual level

A: Each bar represents a chromosome, in terms of M. mulatta genome. Colored bands represent tree topologies of each 100 kb window. Colors correspond to topologies in (B). B: Ten most common trees. Values at top left corner are percentage of all 100 kb windows that recover that topology. Colors correspond to colored bands in (A), with gray and black regions showing other topologies and missing data.

下载: 全尺寸图片幻灯片

Figure 2. MSC (multispecies coalescent) tree

All node support values are 100%. A: MSC species tree generated from ASTRAL and MP-EST based on 26 633 SNV-fragments. B: Species tree with divergence time. Topology and divergence time were both estimated in SNAPP based on 20 000 SNV sites. This tree shows a conflict of Mfas_1 position with (A). Numbers on nodes indicate divergence time. Purple bars on nodes represent 95% confidence interval of divergence time. C: MSC tree at species level.

下载: 全尺寸图片幻灯片

Figure 3. Consensus network of 26 633 SNV-fragment trees with 11% threshold

Cuboid structures mainly occur in fascicularis and sinica species groups, indicating phylogenetic conflicts in these two species groups and potential interspecific gene flow. There is no cuboid structure in the net center, indicating that the evolutionary relationship of ancestral macaques is relatively clear.

下载: 全尺寸图片幻灯片

Figure 4. Gene flow signals in macaques

A: Gene flow identified by D statistic (corrected P<0.001) at individual level. Numbers in grids represent D values, with higher values indicating higher introgression level. Grids without numbers indicate that no gene flow signal was detected. Redder colors indicate higher D statistics. Maximum D value of each individual pair was used for drawing. B: Gene flow identified by D statistic (corrected P<0.001) at species level. The meanings of color and number in grid are the same as that in (A). Maximum D value of each species pair was used for drawing. C: Species tree of macaques with directional gene flow signals. Only signals confirmed by both D and D_FOIL statistics are shown here. Arrows indicate direction of gene flow.

下载: 全尺寸图片幻灯片

Figure 5. Proportion of genome shared through gene flow estimated by f_d statistic at (A) individual level and (B) species level

Number in grid is value of f_d. Grids without numbers indicate that no gene flow signal was detected. The f_d values of species pairs between fascicularis and silenus species groups were higher than that of other species pairs, with M. fascicularis and M. nemestrina species pair showing highest f_d value. In addition, M. fascicularis and M. mulatta species pair showed a high f_d value.

下载: 全尺寸图片幻灯片

Figure 6. Rooted network of macaques

A: Rooted network of macaques with four reticulations inferred by PhyloNetworks based on 26 633 SNV-fragments. Hybrid edges are annotated with their inheritance values, which measure proportion of genes inherited via gene flow. B: Network scores based on different maximum number of reticulations (0–6). We estimated networks with a different maximum number of reticulations, and each generated a network score, with lower scores indicating better networks. However, networks with five and six reticulations could not be re-rooted by P. anubis due to hybrid edges on the P. anubis branch. Therefore, only the network with four reticulations is shown here.

下载: 全尺寸图片幻灯片

Figure 7. Distribution of top 5% of windows with strongest introgression signals according to f_d across chromosome 18

Species of species pairs belong to fascicularis and silenus species groups. Results showed that top 5% of windows with strongest introgression signals for different species pairs had similar genomic distributions.

下载: 全尺寸图片幻灯片

Figure 8. Genome-wide heterozygosity and demographic history

A: Genome-wide heterozygosity estimated from non-overlapping 1 Mb windows. B–D: Historical effective population sizes (N_e) of fascicularis, silenus, and sinica species groups. X-axis represents time; Y-axis represents N_e. Plots were scaled using a mutation rate (μ) of 0.58×10^-8 bp^-1 generation^-1 and a generation time (g) of 10.

下载: 全尺寸图片幻灯片

Table 1. Information on samples and genomic data

Scientific name	Common name	Sample ID	NCBI accession No.	Sex	Sample origin	Sequencing platform	No. of bases (Gb)	Depth*
*M. arctoides*	Stump-tailed macaque	Marc_R02	This study, SAMN15194901	Male	Yunnan, China	Illumina	152.0	~47.0×
		Marc_R19	This study, SAMN15194902	Female	Guangxi, China	Illumina	112.2	~34.7×
M. assamensis	Assamese macaque	Mass	SRR2981114	Male	Yunnan, China	Illumina	154.0	~47.6×
M. fascicularis	Crab-eating macaque	Mfas_1	SRR8194877	Female	Unknown (in captivity in China)	Illumina	92.1	~28.5×
		Mfas_Mau	ERS629711	Male	Mauritius	Illumina	61.6	~19.0×
M. fuscata	Japanese macaque	Mfus	DRR002234	Unknown	Japan	Illumina	142.5	~44.0×
M. mulatta	Rhesus macaque	Mmul_Chi	SRR1944102	Female	China	Illumina	144.5	~44.7×
		Mmul_Ind	SRR1952166	Female	India	Illumina	131.3	~40.6×
M. nemestrina	Southern pig-tailed macaque	Mnem_1	SRR1698391, SRR1698394, SRR1698403, SRR1698405	Female	Unknown	Illumina	152.7	~47.2×
		Mnem_2	SRR5947292	Male	Borneo, Malaysia	Illumina	140.7	~43.5×
M. nigra	Black crested macaque	Mnig	SRR5947294	Female	Sulawesi, Indonesia	Illumina	135.8	~42.0×
*M. thibetana*	Tibetan macaque	Mthi_HT1	This study, SAMN15194903	Female	Anhui, China	Illumina	93.7	~29.0×
		Mthi_R25	This study, SAMN15194904	Female	Guangxi, China	Illumina	113.9	~35.2×
M. tonkeana	Tonkean macaque	Mton	SRR5947293	Male	Sulawesi, Indonesia	Illumina	135.4	~41.8×
P. anubis	Olive baboon	Panu	SRR8723580	Female	Unknown	Illumina	137.9	~42.6×
For individual macaque genome samples, scientific name, common name, sample ID, NCBI accession No., sex, sample origin, sequencing platform, No. of bases, and sequencing depth are shown. New whole-genome sequences of this study are marked in bold. : Calculations were based on total length of M. mulatta* genome assembly Mmul_8.0.1, 3 236 224 332 bp.

下载: 导出CSV

Table 2. SNV information for each analyzed macaque

Sample	Filtered			Downsampled (~15×)
Sample	SNVs	Homo	Het	Callable sites	Het	Heterozygosity	Ts	Tv	Ts/Tv
Marc_R02	7 271 275	5 383 371	1 887 904	2 555 381 332	3 782 713	0.001 480	10 682 013	4 949 053	2.16
Marc_R19	7 000 609	5 675 953	1 324 656	2 553 354 858	2 644 171	0.001 036	10 334 343	4 762 614	2.17
Mass	7 926 468	4 560 039	3 366 429	2 519 264 130	6 121 131	0.002 430	10 831 112	5 023 843	2.16
Mfas_1	6 909 052	3 101 413	3 807 639	2 562 592 812	7 612 441	0.002 971	10 058 278	4 638 571	2.17
Mfas_Mau	6 773 377	3 895 560	2 877 817	2 549 849 925	5 881 316	0.002 307	10 190 936	4 659 300	2.19
Mfus	4 805 372	3 403 338	1 402 034	2 562 072 275	2 619 778	0.001 023	7 074 787	3 279 216	2.16
Mmul_Chi	5 192 005	2 071 981	3 120 024	2 556 851 619	5 748 608	0.002 248	7 168 259	3 273 752	2.19
Mmul_Ind	4 058 527	1 370 638	2 687 889	2 550 406 218	5 072 952	0.001 989	5 723 495	2 602 782	2.20
Mnem_1	8 733 029	4 860 252	3 872 777	2 559 986 484	7 267 811	0.002 839	12 211 436	5 571 807	2.19
Mnem_2	8 568 074	4 907 725	3 660 349	2 557 580 297	7 210 573	0.002 819	12 310 845	5 636 798	2.18
Mnig	7 743 384	6 043 224	1 700 160	2 553 652 584	3 353 047	0.001 313	11 259 320	5 250 264	2.14
Mthi_HT1	6 133 336	5 691 120	442 216	2 488 747 849	903 396	0.000 363	9 401 283	4 277 321	2.20
Mthi_R25	6 858 249	5 921 203	937 046	2 552 204 059	1 886 287	0.000 739	10 137 409	4 730 651	2.14
Mton	8 229 873	5 597 616	2 632 257	2 555 184 660	5 168 771	0.002 023	11 872 755	5 501 580	2.16
Panu	17 507 271	15 461 142	2 046 129	2 529 072 236	3 620 049	0.001 431	25 935 871	11 112 178	2.33
For individual macaque genome samples, short ID, total number of single nucleotide variants (SNVs), number of heterozygous SNVs (Het), number of homozygous SNVs (Homo), and transitions/transversions (Ts/Tv) are shown.

下载: 导出CSV

Table 3. Statistics on top 5% of windows with strongest introgression signals based on f_d for species pairs between fascicularis and silenus species groups

	Species pair	No. of top 5% windows	No. of shared windows	Percentage of shared windows	No. of specific windows	Percentage of specific window
M. fascicularis-silenus group species	M. fascicularis- M. nemestrina	2 920	1 756	60.14	378	12.95
	M. fascicularis- M. nigra	2 585		67.93	225	8.70
	M. fascicularis- M. tonkeana	2 814		62.40	257	9.13
M. nemestrina-fascicularis group species	M. fascicularis- M. nemestrina	2 920	1 382	47.33	378	12.95
	M. fuscata- M. nemestrina	3 015		45.84	646	21.43
	M. mulatta- M. nemestrina	2 999		46.08	446	14.87
For M. fascicularis-silenus group species pairs, 60.14%–67.93% of top 5% of windows were shared, and this proportion for M. nemestrina-fascicularis group species pairs was 45.84%–47.33%. Windows specific to each species pair only accounted for 8.70%–21.43%.

下载: 导出CSV

参考文献(93)

[1]	Abbott R, Albach D, Ansell S, Arntzen JW, Baird SJE, Bierne N, et al. 2013. Hybridization and speciation. Journal of Evolutionary Biology, 26(2): 229−246. doi: 10.1111/j.1420-9101.2012.02599.x
[2]	Ang A, Boonratana R, Choudhury A, Supriatna J. 2020. Macaca nemestrina. The IUCN Red List of Threatened Species 2020: e.T12555A181324867.
[3]	Árnason U, Lammers F, Kumar V, Nilsson MA, Janke A. 2018. Whole-genome sequencing of the blue whale and other rorquals finds signatures for introgressive gene flow. Science Advances, 4(4): eaap9873. doi: 10.1126/sciadv.aap9873
[4]	Arnold ML, Meyer A. 2006. Natural hybridization in primates: one evolutionary mechanism. Zoology (Jena), 109(4): 261−276. doi: 10.1016/j.zool.2006.03.006
[5]	Baiz MD, Tucker PK, Mueller JL, Cortés-Ortiz L. 2020. X-linked signature of reproductive isolation in humans is mirrored in a howler monkey hybrid zone. Journal of Heredity, 111(5): 419−428. doi: 10.1093/jhered/esaa021
[6]	Barley AJ, de Oca ANM, Reeder TW, Manríquez-Morán NL, Monroy JCA, Hernández-Gallegos O, et al. 2019. Complex patterns of hybridization and introgression across evolutionary timescales in Mexican whiptail lizards (Aspidoscelis). Molecular Phylogenetics and Evolution, 132: 284−295. doi: 10.1016/j.ympev.2018.12.016
[7]	Bernsteil IS. 1966. Naturally occurring primate hybrid. Science, 154(3756): 1559−1560. doi: 10.1126/science.154.3756.1559
[8]	Bouckaert R, Heled J, Kühnert D, Vaughan T, Wu CH, Xie D, et al. 2014. BEAST 2: a software platform for Bayesian evolutionary analysis. PLoS Computational Biology, 10(4): e1003537. doi: 10.1371/journal.pcbi.1003537
[9]	Bryant D, Bouckaert R, Felsenstein J, Rosenberg NA, RoyChoudhury A. 2012. Inferring species trees directly from biallelic genetic markers: bypassing gene trees in a full coalescent analysis. Molecular Biology and Evolution, 29(8): 1917−1932. doi: 10.1093/molbev/mss086
[10]	Bunlungsup S, Kanthaswamy S, Oldt RF, Smith DG, Houghton P, Hamada Y, et al. 2017. Genetic analysis of samples from wild populations opens new perspectives on hybridization between long-tailed (Macaca fascicularis) and rhesus macaques (Macaca mulatta). American Journal of Primatology, 79(12): e22726. doi: 10.1002/ajp.22726
[11]	Chen SF, Zhou YQ, Chen YR, Gu J. 2018. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics, 34(17): i884−i890. doi: 10.1093/bioinformatics/bty560
[12]	Chu JH, Lin YS, Wu HY. 2007. Evolution and dispersal of three closely related macaque species, Macaca mulatta, M. cyclopis, and M. fuscata, in the Eastern Asia. Molecular Phylogenetics and Evolution, 43(2): 418−429. doi: 10.1016/j.ympev.2006.11.022
[13]	Ciani AC, Stanyon R, Scheffrahn W, Sampurno B. 1989. Evidence of gene flow between Sulawesi macaques. American Journal of Primatology, 17(4): 257−270. doi: 10.1002/ajp.1350170402
[14]	Cortés-Ortiz L, Duda Jr TF, Canales-Espinosa D, García-Orduña F, Rodríguez-Luna E, Bermingham E. 2007. Hybridization in large-bodied new world primates. Genetics, 176(4): 2421−2425. doi: 10.1534/genetics.107.074278
[15]	Deinard A, Smith DG. 2001. Phylogenetic relationships among the macaques: evidence from the nuclear locus NRAMP1. Journal of Human Evolution, 41(1): 45−59. doi: 10.1006/jhev.2001.0480
[16]	Delson E. 1980. Fossil macaques, phyletic relationships and a scenario of deployment. In: Lindburg DG. The Macaques: Studies in Ecology, Behavior and Evolution. New York: Van Nostrand Reinhold.
[17]	DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. 2011. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature Genetics, 43(5): 491−498. doi: 10.1038/ng.806
[18]	Edelman NB, Frandsen PB, Miyagi M, Clavijo B, Davey J, Dikow RB, et al. 2019. Genomic architecture and introgression shape a butterfly radiation. Science, 366(6465): 594−599. doi: 10.1126/science.aaw2090
[19]	Eudey A, Kumar A, Singh M, Boonratana R. 2020. Macaca fascicularis (Errata Version Published in 2021). The IUCN Red List of Threatened Species 2020: e.T12551A195354635.
[20]	Evans BJ, Tosi AJ, Zeng K, Dushoff J, Corvelo A, Melnick DJ. 2017. Speciation over the edge: gene flow among non-human primate species across a formidable biogeographic barrier. Royal Society Open Science, 4(10): 170351. doi: 10.1098/rsos.170351
[21]	Fan PF, Liu Y, Zhang ZC, Zhao C, Li C, Liu WL, et al. 2017. Phylogenetic position of the white-cheeked macaque (Macaca leucogenys), a newly described primate from southeastern Tibet. Molecular Phylogenetics and Evolution, 107: 80−89. doi: 10.1016/j.ympev.2016.10.012
[22]	Fan ZX, Zhao G, Li P, Osada N, Xing JC, Yi Y, et al. 2014. Whole-genome sequencing of Tibetan macaque (Macaca thibetana) provides new insight into the macaque evolutionary history. Molecular Biology and Evolution, 31(6): 1475−1489. doi: 10.1093/molbev/msu104
[23]	Fan ZX, Zhou AB, Osada N, Yu JQ, Jiang J, Li P, et al. 2018. Ancient hybridization and admixture in macaques (genus Macaca) inferred from whole genome sequences. Molecular Phylogenetics and Evolution, 127: 376−386. doi: 10.1016/j.ympev.2018.03.038
[24]	Felsenstein J. 1989. PHYLIP - phylogeny inference package (Version 3.2). Cladistics, 5(2): 164−166.
[25]	Figueiro HV, Li G, Trindade FJ, Assis J, Pais F, Fernandes G, et al. 2017. Genome-wide signatures of complex introgression and adaptive evolution in the big cats. Science Advances, 3(7): e1700299. doi: 10.1126/sciadv.1700299
[26]	Fooden J. 1976. Provisional classification and key to living species of macaques (primates: Macaca). Folia Primatologica, 25(2–3): 225−236.
[27]	Gante HF, Matschiner M, Malmstrom M, Jakobsen KS, Jentoft S, Salzburger W. 2016. Genomics of speciation and introgression in princess cichlid fishes from Lake Tanganyika. Molecular Ecology, 25(24): 6143−6161. doi: 10.1111/mec.13767
[28]	Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, et al. 2010. A draft sequence of the neandertal genome. Science, 328(5979): 710−722. doi: 10.1126/science.1188021
[29]	Groves C. 2001. Primate Taxonomy. Washington: Smithsonian Institution Press.
[30]	Hamada Y, San AM, Malaivijitnond S. 2016. Assessment of the hybridization between rhesus (Macaca mulatta) and long-tailed macaques (M. fascicularis) based on morphological characters. American Journal of Physical Anthropology, 159(2): 189−198. doi: 10.1002/ajpa.22862
[31]	Hamada Y, Yamamoto A, Kunimatsu Y, Tojima S, Mouri T, Kawamoto Y. 2012. Variability of tail length in hybrids of the Japanese macaque (Macaca fuscata) and the taiwanese macaque (Macaca cyclopis). Primates, 53(4): 397−411. doi: 10.1007/s10329-012-0317-3
[32]	Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS. 2018. UFBoot2: improving the ultrafast bootstrap approximation. Molecular Biology and Evolution, 35(2): 518−522. doi: 10.1093/molbev/msx281
[33]	Holbourn AE, Kuhnt W, Clemens SC, Kochhann KGD, Jöhnck J, Lübbers J, et al. 2018. Late Miocene climate cooling and intensification of southeast Asian winter monsoon. Nature Communications, 9(1): 1584. doi: 10.1038/s41467-018-03950-1
[34]	Ito T, Kanthaswamy S, Bunlungsup S, Oldt RF, Houghton P, Hamada Y, et al. 2020. Secondary contact and genomic admixture between rhesus and long-tailed macaques in the Indochina Peninsula. Journal of Evolutionary Biology, 33(9): 1164−1179. doi: 10.1111/jeb.13681
[35]	Ito T, Lee YJ, Nishimura TD, Tanaka M, Woo JY, Takai M. 2018. Phylogenetic relationship of a fossil macaque (Macaca cf. robusta) from the Korean peninsula to Extant species of macaques based on zygomaxillary morphology. Journal of Human Evolution, 119: 1−13. doi: 10.1016/j.jhevol.2018.02.002
[36]	Jiang J, Yu JQ, Li J, Li P, Fan ZX, Niu LL, et al. 2016. Mitochondrial genome and nuclear markers provide new insight into the evolutionary history of macaques. PLoS One, 11(5): e0154665. doi: 10.1371/journal.pone.0154665
[37]	Junier T, Zdobnov EM. 2010. The newick utilities: high-throughput phylogenetic tree processing in the UNIX shell. Bioinformatics, 26(13): 1669−1670. doi: 10.1093/bioinformatics/btq243
[38]	Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. 2017. ModelFinder: fast model selection for accurate phylogenetic estimates. Nature Methods, 14(6): 587−589. doi: 10.1038/nmeth.4285
[39]	Kubisch HM, Falkenstein KP, Deroche CB, Franke DE. 2012. Reproductive efficiency of captive Chinese- and Indian-origin rhesus macaque (Macaca mulatta) females. American Journal of Primatology, 74(2): 174−184. doi: 10.1002/ajp.21019
[40]	Kuhlwilm M, Han S, Sousa VC, Excoffier L, Marques-Bonet T. 2019. Ancient admixture from an extinct ape lineage into bonobos. Nature Ecology & Evolution, 3(6): 957−965.
[41]	Kumar V, Lammers F, Bidon T, Pfenninger M, Kolter L, Nilsson MA, et al. 2017. The evolutionary history of bears is characterized by gene flow across species. Scientific Reports, 7: 46487. doi: 10.1038/srep46487
[42]	Lambert SM, Streicher JW, Fisher-Reid MC, de la Cruz FRM, Martinez-Méndez N, García-Vázquez UO, et al. 2019. Inferring introgression using RADseq and D_FOIL: Power and pitfalls revealed in a case study of spiny lizards (Sceloporus). Molecular Ecology Resources, 19(4): 818−837. doi: 10.1111/1755-0998.12972
[43]	Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with bowtie 2. Nature Methods, 9(4): 357−359. doi: 10.1038/nmeth.1923
[44]	Lewis PO. 2001. A likelihood approach to estimating phylogeny from discrete morphological character data. Systematic Biology, 50(6): 913−925. doi: 10.1080/106351501753462876
[45]	Lexer C, Widmer A. 2008. Review. The genic view of plant speciation: recent progress and emerging questions. Philosophical transactions of the Royal Society B, 363(1506): 3023−3036. doi: 10.1098/rstb.2008.0078
[46]	Li H. 2011. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics, 27(21): 2987−2993. doi: 10.1093/bioinformatics/btr509
[47]	Li H, Durbin R. 2011. Inference of human population history from individual whole-genome sequences. Nature, 475(7357): 493−496. doi: 10.1038/nature10231
[48]	Li J, Han K, Xing JC, Kim HS, Rogers J, Ryder OA, et al. 2009. Phylogeny of the macaques (Cercopithecidae: Macaca) based on Alu elements. Gene, 448(2): 242−249. doi: 10.1016/j.gene.2009.05.013
[49]	Li QQ, Zhang YP. 2005. Phylogenetic relationships of the macaques (Cercopithecidae: Macaca), Inferred from mitochondrial DNA sequences. Biochemical Genetics, 43(7–8): 375−386.
[50]	Liu L, Yu LL, Edwards SV. 2010. A maximum pseudo-likelihood approach for estimating species trees under the coalescent model. BMC Evolutionary Biology, 10: 302. doi: 10.1186/1471-2148-10-302
[51]	Liu ZJ, Tan XX, Orozco-terWengel P, Zhou XM, Zhang LY, Tian SL, et al. 2018. Population genomics of wild Chinese rhesus macaques reveals a dynamic demographic history and local adaptation, with implications for biomedical research. GigaScience, 7(9): giy106.
[52]	Louys J, Turner A. 2012. Environment, preferred habitats and potential refugia for Pleistocene Homo in southeast Asia. Comptes Rendus Palevol, 11(2–3): 203−211.
[53]	Malinsky M, Matschiner M, Svardal H. 2021. Dsuite - fast D-statistics and related admixture evidence from VCF files. Molecular Ecology Resources, 21(2): 584−595. doi: 10.1111/1755-0998.13265
[54]	Martin SH, Davey JW, Jiggins CD. 2015. Evaluating the use of ABBA-BABA statistics to locate introgressed loci. Molecular Biology and Evolution, 32(1): 244−257. doi: 10.1093/molbev/msu269
[55]	Martin SH, Jiggins CD. 2017. Interpreting the genomic landscape of introgression. Current Opinion in Genetics & Development, 47: 69−74.
[56]	Matsudaira K, Hamada Y, Bunlungsup S, Ishida T, San AM, Malaivijitnond S. 2018. Whole mitochondrial genomic and Y-chromosomal phylogenies of burmese long-tailed macaque (Macaca fascicularis aurea) suggest ancient hybridization between fascicularis and sinica species groups. Journal of Heredity, 109(4): 360−371. doi: 10.1093/jhered/esx108
[57]	Meijaard E. 2003. Mammals of south-east Asian islands and their Late Pleistocene environments. Journal of Biogeography, 30(8): 1245−1257. doi: 10.1046/j.1365-2699.2003.00890.x
[58]	Nakhleh L. 2013. Computational approaches to species phylogeny inference and gene tree reconciliation. Trends in Ecology & Evolution, 28(12): 719−728.
[59]	Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. 2015. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Molecular Biology and Evolution, 32(1): 268−274. doi: 10.1093/molbev/msu300
[60]	Nosil P. 2008. Speciation with gene flow could be common. Molecular Ecology, 17(9): 2103−2106. doi: 10.1111/j.1365-294X.2008.03715.x
[61]	Osada N, Matsudaira K, Hamada Y, Malaivijitnond S. 2021. Testing sex-biased admixture origin of macaque species using autosomal and x-chromosomal genomic sequences. Genome Biology and Evolution, 13(1): evaa209.
[62]	Pabijan M, Zieliński P, Dudek K, Stuglik M, Babik W. 2017. Isolation and gene flow in a speciation continuum in newts. Molecular Phylogenetics and Evolution, 116: 1−12. doi: 10.1016/j.ympev.2017.08.003
[63]	Pease JB, Hahn MW. 2015. Detection and polarization of introgression in a five-taxon phylogeny. Systematic Biology, 64(4): 651−662. doi: 10.1093/sysbio/syv023
[64]	Prado-Martinez J, Sudmant PH, Kidd JM, Li H, Kelley JL, Lorente-Galdos B, et al. 2013. Great ape genetic diversity and population history. Nature, 499(7459): 471−475. doi: 10.1038/nature12228
[65]	Reimand J, Kull M, Peterson H, Hansen J, Vilo J. 2007. g:Profiler—a web-based toolset for functional profiling of gene lists from large-scale experiments. Nucleic Acids Research, 35(S2): W193−W200.
[66]	Rogers J, Raveendran M, Harris RA, Mailund T, Leppälä K, Athanasiadis G, et al. 2019. The comparative genomics and complex population history of Papio baboons. Science Advances, 5(1): eaau6947. doi: 10.1126/sciadv.aau6947
[67]	Roos C, Boonratana R, Supriatna J, Fellowes JR, Groves CP, Nash SD, et al. 2014. An updated taxonomy and conservation status review of Asian primates. Asian Primates Journal, 4(1): 2−38.
[68]	Roos C, Kothe M, Alba DM, Delson E, Zinner D. 2019. The radiation of macaques out of Africa: evidence from mitogenome divergence times and the fossil record. Journal of Human Evolution, 133: 114−132. doi: 10.1016/j.jhevol.2019.05.017
[69]	Rovie-Ryan JJ, Khan FAA, Abdullah MT. 2021. Evolutionary pattern of Macaca fascicularis in southeast Asia inferred using y-chromosomal gene. BMC Ecology and Evolution, 21(1): 26. doi: 10.1186/s12862-021-01757-1
[70]	Schliep KP. 2011. Phangorn: phylogenetic analysis in R. Bioinformatics, 27(4): 592−593. doi: 10.1093/bioinformatics/btq706
[71]	Sniderman JMK, Woodhead JD, Hellstrom J, Jordan GJ, Drysdale RN, Tyler JJ, et al. 2016. Pliocene reversal of late Neogene aridification. Proceedings of the National Academy of Sciences of the United States of America, 113(8): 1999−2004. doi: 10.1073/pnas.1520188113
[72]	Solís-Lemus C, Bastide P, Ané C. 2017. PhyloNetworks: a package for phylogenetic networks. Molecular Biology and Evolution, 34(12): 3292−3298. doi: 10.1093/molbev/msx235
[73]	Stange M, Sánchez-Villagra MR, Salzburger W, Matschiner M. 2018. Bayesian divergence-time estimation with genome-wide single-nucleotide polymorphism data of sea catfishes (Ariidae) supports Miocene closure of the Panamanian isthmus. Systematic Biology, 67(4): 681−699. doi: 10.1093/sysbio/syy006
[74]	Stevison LS, Kohn MH. 2009. Divergence population genetic analysis of hybridization between rhesus and Cynomolgus macaques. Molecular Ecology, 18(11): 2457−2475. doi: 10.1111/j.1365-294X.2009.04212.x
[75]	Tarailo-Graovac M, Chen NS. 2009. Using repeatmasker to identify repetitive elements in genomic sequences. Current Protocols in Bioinformatics, 25(1): 4−10.
[76]	Tosi AJ, Coke CS. 2007. Comparative phylogenetics offer new insights into the biogeographic history of Macaca fascicularis and the origin of the mauritian macaques. Molecular Phylogenetics and Evolution, 42(2): 498−504. doi: 10.1016/j.ympev.2006.08.002
[77]	Tosi AJ, Disotell TR, Morales JC, Melnick DJ. 2003a. Cercopithecine y-chromosome data provide a test of competing morphological evolutionary hypotheses. Molecular Phylogenetics and Evolution, 27(3): 510−521. doi: 10.1016/S1055-7903(03)00024-1
[78]	Tosi AJ, Morales JC, Melnick DJ. 2000. Comparison of Y chromosome and mtDNA phylogenies leads to unique inferences of macaque evolutionary history. Molecular Phylogenetics and Evolution, 17(2): 133−144. doi: 10.1006/mpev.2000.0834
[79]	Tosi AJ, Morales JC, Melnick DJ. 2003b. Paternal, maternal, and biparental molecular markers provide unique windows onto the evolutionary history of macaque monkeys. Evolution, 57(6): 1419−1435. doi: 10.1111/j.0014-3820.2003.tb00349.x
[80]	Trask JAS, Garnica WT, Smith DG, Houghton P, Lerche N, Kanthaswamy S. 2013. Single-nucleotide polymorphisms reveal patterns of allele sharing across the species boundary between rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques. American Journal of Primatology, 75(2): 135−144. doi: 10.1002/ajp.22091
[81]	Vanderpool D, Minh BQ, Lanfear R, Hughes D, Murali S, Harris RA, et al. 2020. Primate phylogenomics uncovers multiple rapid radiations and ancient interspecific introgression. PLoS Biology, 18(12): e3000954. doi: 10.1371/journal.pbio.3000954
[82]	Wang RJ, Thomas GWC, Raveendran M, Harris RA, Doddapaneni H, Muzny DM, et al. 2020. Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability. Genome Research, 30(6): 826−834. doi: 10.1101/gr.255174.119
[83]	Wen DQ, Yu Y, Zhu JF, Nakhleh L. 2018. Inferring phylogenetic networks using PhyloNet. Systematic Biology, 67(4): 735−740. doi: 10.1093/sysbio/syy015
[84]	Woodruff DS. 2010. Biogeography and conservation in southeast Asia: how 2.7 million years of repeated environmental fluctuations affect today’s patterns and the future of the remaining refugial-phase biodiversity. Biodiversity and Conservation, 19(4): 919−941. doi: 10.1007/s10531-010-9783-3
[85]	Xue C, Raveendran M, Harris RA, Fawcett GL, Liu XM, White S, et al. 2016. The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences. Genome Research, 26(12): 1651−1662. doi: 10.1101/gr.204255.116
[86]	Yan GM, Zhang GJ, Fang XD, Zhang YF, Li C, Ling F, et al. 2011. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques. Nature Biotechnology, 29(11): 1019−1023. doi: 10.1038/nbt.1992
[87]	Yang FT, Shi LM. 1994. Studies of the miotic chromosomes, meiosis and spermatogenesis of a macaque hybrid. Acta Genetica Sinica, 21(1): 24−29. (in Chinese)
[88]	Yang ZH. 2007. PAML 4: phylogenetic analysis by maximum likelihood. Molecular Biology and Evolution, 24(8): 1586−1591. doi: 10.1093/molbev/msm088
[89]	Zhang C, Rabiee M, Sayyari E, Mirarab S. 2018. ASTRAL-III: polynomial time species tree reconstruction from partially resolved gene trees. BMC Bioinformatics, 19(S6): 153. doi: 10.1186/s12859-018-2129-y
[90]	Zhang DZ, Song G, Gao B, Cheng YL, Qu YH, Wu SY, et al. 2017. Genomic differentiation and patterns of gene flow between two long-tailed tit species (Aegithalos). Molecular Ecology, 26(23): 6654−6665. doi: 10.1111/mec.14383
[91]	Zhou XM, Meng XH, Liu ZJ, Chang J, Wang BS, Li MZ, et al. 2016. Population genomics reveals low genetic diversity and adaptation to hypoxia in snub-nosed monkeys. Molecular Biology and Evolution, 33(10): 2670−2681. doi: 10.1093/molbev/msw150
[92]	Ziegler T, Abegg C, Meijaard E, Perwitasari-Farajallah D, Walter L, Hodges JK, et al. 2007. Molecular phylogeny and evolutionary history of southeast Asian macaques forming the M. silenus group. Molecular Phylogenetics and Evolution, 42(3): 807−816. doi: 10.1016/j.ympev.2006.11.015
[93]	Zinner D, Arnold ML, Roos C. 2011. The strange blood: natural hybridization in primates. Evolutionary Anthropology: Issues, News, and Reviews, 20(3): 96−103. doi: 10.1002/evan.20301