Relaxed constraint and functional divergence of the progesterone receptor (PGR) in the human stem-lineage


Autoři: Mirna Marinić aff001;  Vincent J. Lynch aff002
Působiště autorů: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL, United States of America aff001;  Department of Biological Sciences, University at Buffalo, SUNY, Buffalo, NY, United States of America aff002
Vyšlo v časopise: Relaxed constraint and functional divergence of the progesterone receptor (PGR) in the human stem-lineage. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008666
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008666

Souhrn

The steroid hormone progesterone, acting through the progesterone receptor (PR), a ligand-activated DNA-binding transcription factor, plays an essential role in regulating nearly every aspect of female reproductive biology. While many reproductive traits regulated by PR are conserved in mammals, Catarrhine primates evolved several derived traits including spontaneous decidualization, menstruation, and a divergent (and unknown) parturition signal, suggesting that PR may also have evolved divergent functions in Catarrhines. There is conflicting evidence, however, whether the progesterone receptor gene (PGR) was positively selected in the human lineage. Here we show that PGR evolved rapidly in the human stem-lineage (as well as other Catarrhine primates), which likely reflects an episode of relaxed selection intensity rather than positive selection. Coincident with the episode of relaxed selection intensity, ancestral sequence resurrection and functional tests indicate that the major human PR isoforms (PR-A and PR-B) evolved divergent functions in the human stem-lineage. These results suggest that the regulation of progesterone signaling by PR-A and PR-B may also have diverged in the human lineage and that non-human animal models of progesterone signaling may not faithfully recapitulate human biology.

Klíčová slova:

Amino acid substitution – Evolutionary rate – Hominins – Luciferase – Multiple alignment calculation – Primates – Progesterone – Sequence alignment


Zdroje

1. Lydon JP, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CA, et al. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 1995 Sep 15;9(18):2266–78. doi: 10.1101/gad.9.18.2266 7557380

2. Conneely OM, Mulac-Jericevic B, Lydon JP, De Mayo FJ. Reproductive functions of the progesterone receptor isoforms: Lessons from knock-out mice. Vol. 179, Molecular and Cellular Endocrinology. 2001. p. 97–103. doi: 10.1016/s0303-7207(01)00465-8 11420134

3. Kubota K, Cui W, Dhakal P, Wolfe MW, Rumi MAK, Vivian JL, et al. Rethinking progesterone regulation of female reproductive cyclicity. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4212–7. doi: 10.1073/pnas.1601825113 27035990

4. Wetendorf M, DeMayo FJ. The progesterone receptor regulates implantation, decidualization, and glandular development via a complex paracrine signaling network. Vol. 357, Molecular and Cellular Endocrinology. 2012. p. 108–18. doi: 10.1016/j.mce.2011.10.028 22115959

5. Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 1990 Jun 1;9(5):1603–14. 2328727

6. Huse B, Verca SB, Matthey P, Rusconi S. Definition of a negative modulation domain in the human progesterone receptor. Mol Endocrinol. 1998;12(9):1334–42. doi: 10.1210/mend.12.9.0164 9731702

7. Giangrande PH, A. Kimbrel E, Edwards DP, McDonnell DP. The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding. Mol Cell Biol. 2000 May 1;20(9):3102–15. doi: 10.1128/mcb.20.9.3102-3115.2000 10757795

8. Abdel-Hafiz H, Takimoto GS, Tung L, Horwitz KB. The inhibitory function in human progesterone receptor N termini binds SUMO-1 protein to regulate autoinhibition and transrepression. J Biol Chem. 2002 Sep 13;277(37):33950–6. doi: 10.1074/jbc.M204573200 12114521

9. Kaya HS, Hantak AM, Stubbs LJ, Taylor RN, Bagchi IC, Bagchi MK. Roles of progesterone receptor A and B isoforms during human endometrial decidualization. Mol Endocrinol. 2015 Jun 1;29(6):882–95. doi: 10.1210/me.2014-1363 25875046

10. Lombardi J. Comparative Vertebrate Reproduction. 1st ed. Boston: Kluwer Academic Publisher; 1998.

11. Renfree M, Shaw G. Reproduction in Monotremes and Marsupials. In: Encyclopedia of Life Sciences. Chichester, UK: John Wiley & Sons, Ltd; 2001.

12. Behringer RR, Eakin GS, Renfree MB. Mammalian diversity: Gametes, embryos and reproduction. Reprod Fertil Dev. 2006;18(1–2):99–107. doi: 10.1071/rd05137 16478607

13. Bradshaw FJ, Bradshaw D. Progesterone and reproduction in marsupials: A review. Vol. 170, General and Comparative Endocrinology. Academic Press Inc.; 2011. p. 18–40. doi: 10.1016/j.ygcen.2010.07.015 20688062

14. Singh RS, Kulathinal RJ. Sex gene pool evolution and speciation: A new paradigm. Genes Genet Syst. 2000;75(3):119–30. doi: 10.1266/ggs.75.119 10984836

15. Torgerson DG, Kulathinal RJ, Singh RS. Mammalian sperm proteins are rapidly evolving: Evidence of positive selection in functionally diverse genes. Mol Biol Evol. 2002 Nov 1;19(11):1973–80. doi: 10.1093/oxfordjournals.molbev.a004021 12411606

16. Meiklejohn CD, Parsch J, Ranz JM, Hartl DL. Rapid evolution of male-biased gene expression in Drosophila. Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9894–9. doi: 10.1073/pnas.1630690100 12907700

17. Mess A, Carter AM. Evolutionary transformations of fetal membrane characters in Eutheria with special reference to Afrotheria. J Exp Zool Part B Mol Dev Evol. 2006 Mar 15;306(2):140–63.

18. Kin K, Maziarz J, Wagner GP. Immunohistological study of the endometrial tromal fibroblasts in the opossum, Monodelphis domestica: Evidence for homology with eutherian stromal fibroblasts. Biol Reprod. 2014 May 1;90(5).

19. Emera D, Romero R, Wagner G. The evolution of menstruation: A new model for genetic assimilation: Explaining molecular origins of maternal responses to fetal invasiveness. BioEssays. 2012 Jan;34(1):26–35. doi: 10.1002/bies.201100099 22057551

20. Strassmann BI. The evolution of endometrial cycles and menstruation. Q Rev Biol. 1996;71(2):181–218. doi: 10.1086/419369 8693059

21. Csapo A. Progesterone “block.” Am J Anat. 1956 Mar;98(2):273–91. doi: 10.1002/aja.1000980206 13326855

22. Csapo AI, Pinto-Dantas CA. The effect of progesterone on the human uterus. Proc Natl Acad Sci U S A. 1965;54(4):1069–76. doi: 10.1073/pnas.54.4.1069 5219818

23. Shynlova O, Lee YH, Srikhajon K, Lye SJ. Physiologic uterine inflammation and labor onset: Integration of endocrine and mechanical signals. Vol. 20, Reproductive Sciences. 2013. p. 154–67. doi: 10.1177/1933719112446084 22614625

24. Hamilton ME. Revising evolutionary narratives: A consideration of alternative assumptions about sexual selection and competition for mates. Am Anthropol. 1984 Sep;86(3):651–62.

25. Mascia-Lees FE, Relethford JH, Sorger T. Evolutionary oerspectives on permanent breast enlargement in human females. Am Anthropol. 1986 Jun;88(2):423–8.

26. Benshoof L, Thornhill R. The evolution of monogamy and concealed ovulation in humans. J Soc Biol Syst. 1979;2(2):95–106.

27. Burley N. The evolution of concealed ovulation. Am Nat. 1979 Dec;114(6):835–58.

28. Graham C, editor. Reproductive Biology of the Great Apes: Comparative and Biomedical Perspectives. 1st ed. Academic Press; 1981.

29. Chen C, Opazo JC, Erez O, Uddin M, Santolaya-Forgas J, Goodman M, et al. The human progesterone receptor shows evidence of adaptive evolution associated with its ability to act as a transcription factor. Mol Phylogenet Evol. 2008 May;47(2):637–49. doi: 10.1016/j.ympev.2007.12.026 18375150

30. Phillips JB, Abbot P, Rokas A. Is preterm birth a human-specific syndrome? Evol Med Public Heal. 2015;2015(1):136–48.

31. Pollard KS, Salama SR, King B, Kern AD, Dreszer T, Katzman S, et al. Forces shaping the fastest evolving regions in the human genome. PLoS Genet. 2006;2(10):1599–611.

32. Clark AG, Glanowski S, Nielsen R, Thomas PD, Kejariwal A, Todd MA, et al. Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios. Science (80-). 2003 Dec 12;302(5652):1960–3.

33. Nielsen R, Bustamante C, Clark AG, Glanowski S, Sackton TB, Hubisz MJ, et al. A scan for positively selected genes in the genomes of humans and chimpanzees. Tyler-Smith C, editor. PLoS Biol. 2005 May 3;3(6):0976–85.

34. Bakewell MA, Shi P, Zhang J. More genes underwent positive selection in chimpanzee evolution than in human evolution. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7489–94. doi: 10.1073/pnas.0701705104 17449636

35. Arbiza L, Dopazo J, Dopazo H. Positive selection, relaxation, and acceleration in the evolution of the human and chimp genome. PLoS Comput Biol. 2006;2(4):288–300.

36. George RD, McVicker G, Diederich R, Ng SB, MacKenzie AP, Swanson WJ, et al. Trans genomic capture and sequencing of primate exomes reveals new targets of positive selection. Genome Res. 2011 Oct;21(10):1686–94. doi: 10.1101/gr.121327.111 21795384

37. Van Der Lee R, Wiel L, Van Dam TJP, Huynen MA. Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts. Nucleic Acids Res. 2017 Oct 13;45(18):10634–48. doi: 10.1093/nar/gkx704 28977405

38. Kosiol C, Vinař T, Da Fonseca RR, Hubisz MJ, Bustamante CD, Nielsen R, et al. Patterns of positive selection in six mammalian genomes. PLoS Genet. 2008 Aug;4(8).

39. Pohnke Y, Kempf R, Gellersen B. CCAAT/enhancer-binding proteins are mediators in the protein kinase A- dependent activation of the decidual prolactin promoter. J Biol Chem. 1999 Aug 27;274(35):24808–18. doi: 10.1074/jbc.274.35.24808 10455153

40. Christian M, Pohnke Y, Kempf R, Gellersen B, Brosens JJ. Functional association of PR and CCAAT/Enhancer-Binding Proteinβ isoforms: Promoter-dependent cooperation between PR-B and Liver-Enriched Inhibitory Protein, or Liver-Enriched Activatory Protein and PR-A in human endometrial stromal cells. Mol Endocrinol. 2002 Jan 1;16(1):141–54. doi: 10.1210/mend.16.1.0763 11773445

41. Christian M, Zhang X, Schneider-Merck T, Unterman TG, Gellersen B, White JO, et al. Cyclic AMP-induced forkhead transcription factor, FKHR, cooperates with CCAAT/enhancer-binding protein beta in differentiating human endometrial stromal cells. J Biol Chem. 2002;277(23):20825–32. doi: 10.1074/jbc.M201018200 11893744

42. Lynch VJ, Brayer K, Gellersen B, Wagner GP. HoxA-11 and FOXO1A cooperate to regulate decidual prolactin expression: Towards inferring the core transcriptional regulators of decidual genes. PLoS One. 2009;4(9):4–11.

43. Jiang Y, Hu Y, Zhao J, Zhen X, Yan G, Sun H. The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells. Biochem Biophys Res Commun. 2011 Jan 14;404(2):628–33. doi: 10.1016/j.bbrc.2010.12.027 21146499

44. Kosakovsky Pond SL, Frost SDW, Muse S V. HyPhy: Hypothesis testing using phylogenies. Bioinformatics. 2005 Mar 1;21(5):676–9. doi: 10.1093/bioinformatics/bti079 15509596

45. Kosakovsky Pond SL, Murrell B, Fourment M, Frost SDW, Delport W, Scheffler K. A random effects branch-site model for detecting episodic diversifying selection. Mol Biol Evol. 2011 Nov;28(11):3033–43. doi: 10.1093/molbev/msr125 21670087

46. Murrell B, Weaver S, Smith MD, Wertheim JO, Murrell S, Aylward A, et al. Gene-wide identification of episodic selection. Mol Biol Evol. 2015 May 1;32(5):1365–71. doi: 10.1093/molbev/msv035 25701167

47. Kosakovsky Pond SL, Frost SDW. Not so different after all: A comparison of methods for detecting amino acid sites under selection. Mol Biol Evol. 2005 May;22(5):1208–22. doi: 10.1093/molbev/msi105 15703242

48. Murrell B, Moola S, Mabona A, Weighill T, Sheward D, Kosakovsky Pond SL, et al. FUBAR: A fast, unconstrained bayesian AppRoximation for inferring selection. Mol Biol Evol. 2013 May;30(5):1196–205. doi: 10.1093/molbev/mst030 23420840

49. Murrell B, Wertheim JO, Moola S, Weighill T, Scheffler K, Kosakovsky Pond SL. Detecting individual sites subject to episodic diversifying selection. PLoS Genet. 2012 Jul;8(7).

50. Wertheim JO, Murrell B, Smith MD, Pond SLK, Scheffler K. RELAX: Detecting relaxed selection in a phylogenetic framework. Mol Biol Evol. 2015;32(3):820–32. doi: 10.1093/molbev/msu400 25540451

51. Kircher M, Witten DM, Jain P, O’roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46(3):310–5. doi: 10.1038/ng.2892 24487276

52. Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: Predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2019 Jan 8;47(D1):D886–94. doi: 10.1093/nar/gky1016 30371827

53. Li J, Hong X, Mesiano S, Muglia LJ, Wang X, Snyder M, et al. Natural selection has differentiated the progesterone receptor among human populations. Am J Hum Genet. 2018 Jul 5;103(1):45–57. doi: 10.1016/j.ajhg.2018.05.009 29937092

54. Wagner GP, Tong Y, Emera D, Romero R. An evolutionary test of the isoform switching hypothesis of functional progesterone withdrawal for parturition: Humans have a weaker repressive effect of PR-A than mice. J Perinat Med. 2012 Jun;40(4):345–51. doi: 10.1515/jpm-2011-0256 22752763

55. Ratajczak CK, Fay JC, Muglia LJ. Preventing preterm birth: The past limitations and new potential of animal models. DMM Dis Model Mech. 2010;3(7–8):407–14. doi: 10.1242/dmm.001701 20610693

56. Romero R, Scoccia B, Mazor M, Wu YK, Benveniste R. Evidence for a local change in the progesterone/ estrogen ratio in human parturition at term. Am J Obstet Gynecol. 1988;159(3):657–60. doi: 10.1016/s0002-9378(88)80029-2 2971319

57. Mazor M, Hershkovitz R, Chaim W, Levy J, Sharony Y, Leiberman JR, et al. Human preterm birth is associated with systemic and local changes in progesterone/17β-estradiol ratios. Am J Obstet Gynecol. 1994 Jul;171(1):231–6. doi: 10.1016/0002-9378(94)90474-x 8030704

58. Burton RM, Westphal U. Steroid hormone-binding proteins in blood plasma. Metabolism. 1972;21(3):253–76. doi: 10.1016/0026-0495(72)90048-0 4551331

59. Popp RA, Foresman KR, Wise LD, Daniel JC. Amino acid sequence of a progesterone-binding protein. Proc Natl Acad Sci U S A. 1978;75(11):5516–9. doi: 10.1073/pnas.75.11.5516 281700

60. Heap RB, Ackland N, Weir BJ. Progesterone-binding proteins in plasma of guinea-pigs and other hystricomorph rodents. J Reprod Fertil. 1981;63(2):477–89. doi: 10.1530/jrf.0.0630477 6170753

61. Perrot-Applanat M, David-Ferreira JF. Immunocytochemical localization of progesterone-binding protein (PBP) in guinea-pig placental tissue. Cell Tissue Res. 1982 Apr;223(3):627–39. doi: 10.1007/bf00218482 6178511

62. Benassayag C, Souski I, Mignot T-M, Robert B, Hassid J, Duc-Goiran P, et al. Corticosteroid-binding globulin status at the fetomaternal interface during human term pregnancy. Biol Reprod. 2001 Mar 1;64(3):812–21. doi: 10.1095/biolreprod64.3.812 11207196

63. Condon JC, Jeyasuria P, Faust JM, Wilson JW, Mendelson CR. A decline in the levels of progesterone receptor coactivators in the pregnant uterus at term may antagonize progesterone receptor function and contribute to the initiation of parturition. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9518–23. doi: 10.1073/pnas.1633616100 12886011

64. Haluska GJ, West NB, Novy MJ, Brenner RM. Uterine estrogen receptors are increased by ru486 in late pregnant rhesus macaques but not after spontaneous labor. J Clin Endocrinol Metab. 1990;70(1):181–6. doi: 10.1210/jcem-70-1-181 2294130

65. Allport VC. Human labour is associated with nuclear factor-kappaB activity which mediates cyclo-oxygenase-2 expression and is involved with the “functional progesterone withdrawal.” Mol Hum Reprod. 2001 Jun 1;7(6):581–6. doi: 10.1093/molehr/7.6.581 11385114

66. Haluska GJ, Wells TR, Hirst JJ, Brenner RM, Sadowsky DW, Novy MJ. Progesterone receptor localization and isoforms in myometrium, decidua, and fetal membranes from rhesus macaques: Evidence for functional progesterone withdrawal at parturition. J Soc Gynecol Investig. 2002;9(3):125–36. 12009386

67. Merlino AA, Welsh TN, Tan H, Li JY, Cannon V, Mercer BM, et al. Nuclear progesterone receptors in the human pregnancy myometrium: Evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A. J Clin Endocrinol Metab. 2007;92(5):1927–33. doi: 10.1210/jc.2007-0077 17341556

68. Nadeem L, Shynlova O, Matysiak-Zablocki E, Mesiano S, Dong X, Lye S. Molecular evidence of functional progesterone withdrawal in human myometrium. Nat Commun. 2016 May 25;7:11565. doi: 10.1038/ncomms11565 27220952

69. Zakar T, Hertelendy F. Progesterone withdrawal: key to parturition. Vol. 196, American Journal of Obstetrics and Gynecology. 2007. p. 289–96. doi: 10.1016/j.ajog.2006.09.005 17403397

70. Zeng Z, Velarde MC, Simmen FA, Simmen RCM. Delayed parturition and altered myometrial Progesterone Receptor Isoform A expression in mice null for Krüppel-Like Factor 91. Biol Reprod. 2008 Jun 1;78(6):1029–37. doi: 10.1095/biolreprod.107.065821 18305227

71. Pieber D, Allport VC, Hills F, Johnson M, Bennet PR. Interactions between progesterone receptor isoforms in myometrial cells in human labour. Mol Hum Reprod. 2001 Sep 1;7(9):875–9. doi: 10.1093/molehr/7.9.875 11517295

72. Mesiano S, Chan EC, Fitter JT, Kwek K, Yeo G, Smith R. Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium. J Clin Endocrinol Metab. 2002 Jun;87(6):2924–30. doi: 10.1210/jcem.87.6.8609 12050275

73. Mesiano S. Myometrial progesterone responsiveness and the control of human parturition. Vol. 11, Journal of the Society for Gynecologic Investigation. 2004. p. 193–202. doi: 10.1016/j.jsgi.2003.12.004 15120691

74. Mittal P, Romero R, Tarca AL, Gonzalez J, Draghici S, Xu Y, et al. Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term. J Perinat Med. 2010 Nov;38(6):617–43. doi: 10.1515/JPM.2010.097 20629487

75. Brubaker D, Barbaro A, R. Chance M, Mesiano S. A dynamical systems model of progesterone receptor interactions with inflammation in human parturition. BMC Syst Biol. 2016 Aug 19;10(1).

76. Peters GA, Yi L, Skomorovska-Prokvolit Y, Patel B, Amini P, Tan H, et al. Inflammatory stimuli increase progesterone receptor-a stability and transrepressive activity in myometrial cells. Endocrinology. 2017 Jan 1;158(1):158–69. doi: 10.1210/en.2016-1537 27886516

77. Patel B, Peters GA, Skomorovska-Prokvolit Y, Yi L, Tan H, Yousef A, et al. Control of Progesterone Receptor-A transrepressive activity in myometrial cells: Implications for the control of human parturition. Reprod Sci. 2018;25(2):214–21. doi: 10.1177/1933719117716775 28671036

78. Dudley DJ, Branch DW, Edwin SS, Mitchell MD. Induction of preterm birth in mice by RU486. Biol Reprod. 1996 Nov 1;55(5):992–5. doi: 10.1095/biolreprod55.5.992 8902208

79. Yang B, Zhou HJ, He QJ, Fang RY. Termination of early pregnancy in the mouse, rat and hamster with DL111-IT and RU486. Contraception. 2000;62(4):211–6. doi: 10.1016/s0010-7824(00)00160-8 11137076

80. Shynlova O, Nedd-Roderique T, Li Y, Dorogin A, Lye SJ. Myometrial immune cells contribute to term parturition, preterm labour and post-partum involution in mice. J Cell Mol Med. 2013 Jan;17(1):90–102. doi: 10.1111/j.1582-4934.2012.01650.x 23205502

81. Maria B, Stampf F, Goepp A, Ulmann A. Termination of early pregnancy by a single dose of mifepristone (RU 486), a progesterone antagonist. Eur J Obstet Gynecol Reprod Biol. 1988;28(3):249–55. doi: 10.1016/0028-2243(88)90035-4 3208966

82. Vegeto E, Shahbaz MM, Wen DX, Goldman ME, O’Malley BW, McDonnell DP. Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function. Mol Endocrinol. 1993 Oct;7(10):1244–55. doi: 10.1210/mend.7.10.8264658 8264658

83. Wen DX, Xu YF, Mais DE, Goldman ME, McDonnell DP. The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells. Mol Cell Biol. 1994 Dec;14(12):8356–64. doi: 10.1128/mcb.14.12.8356 7969170

84. Rinehart CA, Lyn-Cook JRBD, Kaufman DG. Gland Formation From Human Endometrial Epithelial Cells in vitro. Vitr Cell Dev Biol. 1988;24(10).

85. Boretto M, Cox B, Noben M, Hendriks N, Fassbender A, Roose H, et al. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Dev. 2017;144(10):1775–86.

86. Turco MY, Gardner L, Hughes J, Cindrova-Davies T, Gomez MJ, Farrell L, et al. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nat Cell Biol. 2017 May 1;19(5):568–77. doi: 10.1038/ncb3516 28394884

87. Turco MY, Gardner L, Kay RG, Hamilton RS, Prater M, Hollinshead MS, et al. Trophoblast organoids as a model for maternal–fetal interactions during human placentation. Vol. 564, Nature. Nature Publishing Group; 2018. p. 263–81. doi: 10.1038/s41586-018-0753-3 30487605

88. Marinic M, Lynch VJ. Derivation of endometrial gland organoids from term post-partum placenta. bioRxiv. 2019;753780.

89. Delport W, Poon AFY, Frost SDW, Kosakovsky Pond SL. Datamonkey 2010: A suite of phylogenetic analysis tools for evolutionary biology. Bioinformatics. 2010 Jul 29;26(19):2455–7. doi: 10.1093/bioinformatics/btq429 20671151

90. Smith MD, Wertheim JO, Weaver S, Murrell B, Scheffler K, Kosakovsky Pond SL. Less is more: An adaptive branch-site random effects model for efficient detection of episodic diversifying selection. Mol Biol Evol. 2015 May 1;32(5):1342–53. doi: 10.1093/molbev/msv022 25697341

91. Venkat A, Hahn MW, Thornton JW. Multinucleotide mutations cause false inferences of lineage-specific positive selection. Nat Ecol Evol. 2018 Aug 1;2(8):1280–8. doi: 10.1038/s41559-018-0584-5 29967485

92. Ho J, Tumkaya T, Aryal S, Choi H, Claridge-Chang A. Moving beyond P values: data analysis with estimation graphics. Vol. 16, Nature Methods. Nature Publishing Group; 2019. p. 565–6. doi: 10.1038/s41592-019-0470-3 31217592


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 4

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se