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Normal and altered masticatory load impact on the range of craniofacial shape variation: An analysis of pre-Hispanic and modern populations of the American Southern Cone


Autoři: Andrea P. Eyquem aff001;  Susan C. Kuzminsky aff003;  José Aguilera aff005;  Williams Astudillo aff005;  Viviana Toro-Ibacache aff001
Působiště autorů: Centro de Análisis Cuantitativo en Antropología Dental, Facultad de Odontología, Universidad de Chile, Santiago, Chile aff001;  Max Planck Weizmann Center for Integrative Archaeology and Anthropology, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany aff002;  Department of Anthropology and Applied Archaeology, Eastern New Mexico University, Portales, New Mexico, United States of America aff003;  Anthropology Department, University of California, Santa Cruz, California, United States of America aff004;  Facultad de Medicina and Hospital Clínico, Universidad de Chile, Santiago, Chile aff005;  Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225369

Souhrn

The reduction of masticatory load intensity resulting from dietary changes in human evolution has been proposed as an important factor that alters craniofacial shape in past and current populations. However, its impact on craniofacial variation and on the perceived differences among populations is unclear. The maxillomandibular relationship, which alters masticatory force direction, is a factor often neglected but it can contribute to variation in craniofacial morphology, particularly among modern/urban populations where the prevalence of dental malocclusions is greater than in prehistoric populations. This study investigates the influence of masticatory load intensity and maxillomandibular relationship as a proxy for force direction on the human craniofacial skeleton. By using 3D imaging and geometric morphometrics, we analyzed craniofacial shape variation among 186 individuals from pre-Hispanic and modern Chilean and Argentinean populations that differ in diet consistency (a proxy for masticatory load intensity) and maxillomandibular relationship. We predicted that masticatory load would have a subtle effect on the upper craniofacial bones and that this would be more marked in the maxilla. Our results showed no clear influence of masticatory load on craniofacial shape, particularly in modern/urban populations. Allometry, on the contrary, shows a stronger effect. The degree of integration between the upper craniofacial bones and the load-bearing maxilla depends on masticatory load intensity, decreasing from high to low but showing a conservative pattern of covariation among the groups. The degree of variation in the shape of the maxilla is greater than the upper craniofacial bones. These results suggest that masticatory load has a limited effect in determining differences in craniofacial morphology among populations. This effect is slightly greater for the maxillary region of the face. We propose that the reduction of functional constraints is key to greater shape variation found in modern/urban populations.

Klíčová slova:

Principal component analysis – Diet – Face – Chile (country) – Eating – Mandible – Maxilla


Zdroje

1. Neves WA, Hubbe M. Cranial morphology of early Americans from Lagoa Santa, Brazil: Implications for the settlement of the New World. Proceedings of the National Academy of Sciences. 2005;102(51):18309–14. doi: 10.1073/pnas.0507185102 16344464

2. Chatters JC, Kennett D, Asmerom Y, Kemp B, Plolyak V, Nava Blank A, et al. Late Pleistocene Human Skeleton and mtDNA Link Paleoamericans and Modern Native Americans. Science. 2014;344(6185):750–4. doi: 10.1126/science.1252619 24833392

3. von Cramon-Taubadel N, Strauss A, Hubbe M. Evolutionary population history of early Paleoamerican cranial morphology. Sci Adv. 2017;3(2):e1602289. Epub 2017/03/07. doi: 10.1126/sciadv.1602289 28261661; PubMed Central PMCID: PMC5321447.

4. Kuzminsky SC, Coonerty N, Fehren-Schmitz L. A reassessment of human cranial indices through the Holocene and their implications for the peopling of South America. Journal of Archaeological Science: Reports. 2017;11:709–16. doi: 10.1016/j.jasrep.2016.12.039

5. Hubbe M, Strauss A, Hubbe A, Neves WA. Early South Americans Cranial Morphological Variation and the Origin of American Biological Diversity. PLOS ONE. 2015;10(10):e0138090. doi: 10.1371/journal.pone.0138090 26465141

6. Weaver TD, Roseman CC, Stringer CB. Were neandertal and modern human cranial differences produced by natural selection or genetic drift? Journal of human evolution. 2007;53(2):135–45. doi: 10.1016/j.jhevol.2007.03.001 17512036

7. Menendez L. Moderate climate signature in cranial anatomy of late holocene human populations from Southern South America. Am J Phys Anthropol. 2018. Epub 2017/11/09. doi: 10.1002/ajpa.23355 29115678.

8. Katz DC, Grote MN, Weaver TD. A mixed model for the relationship between climate and human cranial form. Am J Phys Anthropol. 2016;160(4):593–603. Epub 2015/12/03. doi: 10.1002/ajpa.22896 26626704.

9. Harvati K, Weaver TD. Human cranial anatomy and the differential preservation of population history and climate signatures. The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology: An Official Publication of the American Association of Anatomists. 2006;288(12):1225–33. doi: 10.1002/ar.a.20395 17075844

10. Jung H, von Cramon-Taubadel N. Comparison of cranial fluctuating asymmetry between normal and pathological specimens from a modern Thai skeletal group. HOMO. 2018;69(4):188–97. doi: 10.1016/j.jchb.2018.07.004 30097171

11. Larsen CS. The agricultural revolution as environmental catastrophe: Implications for health and lifestyle in the Holocene. Quaternary International. 2006;150(1):12–20. doi: 10.1016/j.quaint.2006.01.004

12. Pinhasi R, Eshed V, von Cramon-Taubadel N. Incongruity between affinity patterns based on mandibular and lower dental dimensions following the transition to agriculture in the Near East, Anatolia and Europe. PLoS One. 2015;10(2):e0117301. Epub 2015/02/05. doi: 10.1371/journal.pone.0117301 25651540; PubMed Central PMCID: PMC4317182.

13. Corruccini RS. An epidemiologic transition in dental occlusion in world populations. American Journal of Orthodontics. 1984;86(5):419–26. doi: 10.1016/s0002-9416(84)90035-6 6594064

14. von Cramon‐Taubadel N. The relative efficacy of functional and developmental cranial modules for reconstructing global human population history. American Journal of Physical Anthropology. 2011;146(1):83–93. doi: 10.1002/ajpa.21550 21710659

15. Sarig R, Slon V, Abbas J, May H, Shpack N, Vardimon AD, et al. Malocclusion in Early Anatomically Modern Human: A Reflection on the Etiology of Modern Dental Misalignment. PLOS ONE. 2013;8(11):e80771. doi: 10.1371/journal.pone.0080771 24278319

16. Toro-Ibacache V, Cortés Araya J, Díaz Muñoz A, Manríquez Soto G. Morphologic variability of nonsyndromic operated patients affected by cleft lip and palate: A geometric morphometric study. American Journal of Orthodontics and Dentofacial Orthopedics. 2014;146(3):346–54. doi: 10.1016/j.ajodo.2014.06.002 25172257

17. Díaz Muñoz A, Manríquez Soto G. Skeletodental Diagnosis Using a Geometric Morphometric Approach. International journal of odontostomatology. 2014;8:05–11.

18. Morales C. Morfología de la sección transversal mandibular en poblaciones actuales y arqueológicas que ejercen distintas intensidades de cargas masticatorias de acuerdo a su dieta: Universidad de Chile; 2018.

19. Toro-Ibacache V, Ugarte F, Morales C, Eyquem A, Aguilera J, Astudillo W. Dental malocclusions are not just about small and weak bones: assessing the morphology of the mandible with cross-section analysis and geometric morphometrics. Clinical Oral Investigations. 2019. doi: 10.1007/s00784-018-2766-6 30604093

20. Thilander B, Myrberg N. The prevalence of malocclusion in Swedish schoolchildren. European Journal of Oral Sciences. 1973;81(1):12–20. doi: 10.1111/j.1600-0722.1973.tb01489.x 4510864

21. Traebert ES, Peres MA. Prevalence of malocclusions and their impact on the quality of life of 18-year-old young male adults of Florianopolis, Brazil. Oral health & preventive dentistry. 2005;3(4).

22. Thilander B, Pena L, Infante C, Parada SS, de Mayorga C. Prevalence of malocclusion and orthodontic treatment need in children and adolescents in Bogota, Colombia. An epidemiological study related to different stages of dental development2001. 153–67 p.

23. Helm S, Prydsö U. Prevalence of malocclusion in medieval and modern Danes contrasted. European Journal of Oral Sciences. 1979;87(2):91–7.

24. Vodanović M, Galić I, Strujić M, Peroš K, Šlaus M, Brkić H. Orthodontic anomalies and malocclusions in Late Antique and Early Mediaeval period in Croatia. Archives of oral biology. 2012;57(4):401–12. doi: 10.1016/j.archoralbio.2011.09.006 21975118

25. Ueki K, Nakagawa K, Takatsuka S, Yamamoto E, Laskin DM. Comparison of the stress direction on the TMJ in patients with class I, II, and III skeletal relationships. Orthodontics & craniofacial research. 2008;11(1):43–50.

26. Spassov A, Toro-Ibacache V, Krautwald M, Brinkmeier H, Kupczik K. Congenital muscle dystrophy and diet consistency affect mouse skull shape differently. J Anat. 2017;231(5):736–48. Epub 2017/08/02. doi: 10.1111/joa.12664 28762259.

27. Martínez-Abadías N, Esparza M, Sjøvold T, González-José R, Santos M, Hernández M, et al. Pervasive genetic integration directs the evolution of the human skull shape. Evolution. 2012;66(4):1010–23. doi: 10.1111/j.1558-5646.2011.01496.x 22486686

28. Rot-Nikcavic I, Downing K, Hall B, Kablar B. Development of the mouse mandibles and clavicles in the absence of skeletal myogenesis. Histology and histopathology. 2007;22(1–3):51–60. doi: 10.14670/HH-22.51 17128411

29. Lacruz RS, Bromage TG, O’Higgins P, Toro-Ibacache V, Warshaw J, Berger LR. Distinct growth of the nasomaxillary complex in Au. sediba. Scientific reports. 2015;5:15175. doi: 10.1038/srep15175 26469387

30. Toro-Ibacache V, Zapata Muñoz V, O’Higgins P. The relationship between skull morphology, masticatory muscle force and cranial skeletal deformation during biting. Annals of Anatomy-Anatomischer Anzeiger. 2016;203:59–68. doi: 10.1016/j.aanat.2015.03.002 25829126

31. Moreno Uribe L, Miller S. Genetics of the dentofacial variation in human malocclusion. Orthodontics & craniofacial research. 2015;18:91–9.

32. Xue F, Wong R, Rabie A. Genes, genetics, and Class III malocclusion. Orthodontics & craniofacial research. 2010;13(2):69–74.

33. da Fontoura CG, Miller S, Wehby G, Amendt B, Holton N, Southard T, et al. Candidate gene analyses of skeletal variation in malocclusion. Journal of dental research. 2015;94(7):913–20. doi: 10.1177/0022034515581643 25910506

34. Morales N, Toro-Ibacache V. La Transición a la Agricultura y la Industrialización Cambiaron la Cara del Ser Humano. ¿Puede el Vegetarianismo ser un Nuevo Factor de Cambio?. Revisión de la Literatura. International Journal of Morphology. 2018;36(1):35–40.

35. Godinho RM, Fitton LC, Toro-Ibacache V, Stringer CB, Lacruz RS, Bromage TG, et al. The biting performance of Homo sapiens and Homo heidelbergensis. J Hum Evol. 2018;118:56–71. Epub 2018/04/03. doi: 10.1016/j.jhevol.2018.02.010 29606203.

36. von Cramon-Taubadel N. Measuring the effects of farming on human skull morphology. Proc Natl Acad Sci U S A. 2017. Epub 2017/08/16. doi: 10.1073/pnas.1711475114 28811377; PubMed Central PMCID: PMC5576842.

37. Paschetta C, De Azevedo S, Gonzalez M, Quinto-Sanchez M, Cintas C, Varela H, et al. Shifts in subsistence type and its impact on the human skull's morphological integration. Am J Hum Biol. 2016;28(1):118–28. Epub 2015/07/02. doi: 10.1002/ajhb.22746 26126704.

38. von Cramon-Taubadel N. Global human mandibular variation reflects differences in agricultural and hunter-gatherer subsistence strategies. Proceedings of the National Academy of Sciences. 2011;108(49):19546–51. doi: 10.1073/pnas.1113050108 22106280

39. Galland M, van Gerven D, von Cramon-Taubadel N, Pinhasi R. 11,000 years of craniofacial and mandibular variation in Lower Nubia. Scientific Reports. 2016;6(1). doi: 10.1038/srep31040 27503560

40. Paschetta C, de Azevedo S, Castillo L, Martínez‐Abadías N, Hernández M, Lieberman DE, et al. The influence of masticatory loading on craniofacial morphology: A test case across technological transitions in the Ohio valley. American Journal of Physical Anthropology: The Official Publication of the American Association of Physical Anthropologists. 2010;141(2):297–314. doi: 10.1002/ajpa.21151 19902454

41. Stansfield E, Evteev A, O’Higgins P. Can diet be inferred from the biomechanical response to simulated biting in modern and pre-historic human mandibles? Journal of Archaeological Science: Reports. 2018. doi: 10.1016/j.jasrep.2018.07.019

42. May H, Sella-Tunis T, Pokhojaev A, Peled N, Sarig R. Changes in mandible characteristics during the terminal Pleistocene to Holocene Levant and their association with dietary habits. Journal of Archaeological Science: Reports. 2018. doi: 10.1016/j.jasrep.2018.03.020

43. Sella-Tunis T, Pokhojaev A, Sarig R, O’Higgins P, May H. Human mandibular shape is associated with masticatory muscle force. Scientific Reports. 2018;8(1):6042. doi: 10.1038/s41598-018-24293-3 29662127

44. Mitteroecker P, Gunz P. Advances in geometric morphometrics. Evolutionary Biology. 2009;36(2):235–47. doi: 10.1007/s11692-009-9055-x

45. Toro Ibacache MV, Manriquez Soto G, Suazo Galdames I. Morfometría geométrica y el estudio de las formas biológicas: de la morfología descriptiva a la morfología cuantitativa. International Journal of Morphology. 2010;28(4):977–90. doi: 10.4067/S0717-95022010000400001

46. Monteiro C, Bertazzy R, Moreira R, Rugani I, Cannon G. A new classification of foods based on the extent and purpose of their processing. Cad Saúde Pública. 2010;26:2039–49. doi: 10.1590/s0102-311x2010001100005 21180977

47. Agrawall KR, Lucas P, Bruce I, Prinz J. Food Properties that Influence Neuromuscular Activity During Human Mastication. Journal of Dental Restauration. 1998;77(11):1931–8. doi: 10.1177/00220345980770111101 9823733

48. Foster KD, Woda A, Peyron M-A. Effect of texture of plastic and elastic model foods on the parameters of mastication. Journal of Neurophysiology. 2006;95(6):3469–79. doi: 10.1152/jn.01003.2005 16709719

49. Schiappacasse V, Niemeyer H. El Arcaico en el norte semiárido de Chile: un comentario. Chungara. 1986:95–8.

50. Kuzminsky SC, Reyes Baez O, Arriaza B, Mendez C, Standen VG, San Roman M, et al. Investigating cranial morphological variation of early human skeletal remains from Chile: A 3D geometric morphometric approach. Am J Phys Anthropol. 2018;165(2):223–37. Epub 2017/11/02. doi: 10.1002/ajpa.23344 29090737.

51. Reyes O, Moraga M, Méndez C, Cherkinsky A. Maritime Hunter-Gatherers in the Chonos Archipelago (43°50’–46°50’ S), Western Patagonian Channels. The Journal of Island and Coastal Archaeology. 2015;10(2):207–31. doi: 10.1080/15564894.2014.1001920

52. Aspillaga E, Castro M, Rodriguez M, Ocampo C. Paleopatología y estilo de vida: El ejemplo de los Chonos. Magallania (Punta Arenas). 2006;34(1). doi: 10.4067/s0718-22442006000100005

53. Barrientos G, Béguelin M, Gordón F, editors. Tendencias cronológicas en el registro bioarqueológico del noreste de Patagonia. IX Jornadas Nacionales de Antropología Biológica; 2009.

54. Gordón F, Tessone A, Béguelin M, Arrigoni G, Guichón R. Paleodietas humanas en la costa patagónica durante el Holoceno tardío. Nuevos datos de isótopos estables y fechados radiocarbónicos para la costa centro-sur. Intersecciones en Antropología. 2015;16:327–38.

55. Marangoni A, Belli ML, Caramelli D, Moggi-Cecchi J, Zavattaro M, Manzi G. Tierra del Fuego, its ancient inhabitants, and the collections of skeletal remains in the Museums of Anthropology of Florence and Rome. Museologia Scientifica. 2011;5(1–2):88–96.

56. Planella MT, Falabella F, Belmar C, Quiroz L. Huertos, chacras y sementeras. Plantas cultivadas y su participación en los desarrollos culturales de Chile central. Revista Española de Antropología Americana. 2015;44(2). doi: 10.5209/rev_REAA.2014.v44.n2.50727

57. Gonzalez-Jose R, Ramirez-Rozzi F, Sardi M, Martinez-Abadias N, Hernandez M, Pucciarelli HM. Functional-cranial approach to the influence of economic strategy on skull morphology. Am J Phys Anthropol. 2005;128(4):757–71. Epub 2005/07/20. doi: 10.1002/ajpa.20161 16028224.

58. Uribe M, Agüero C, Catalán D, Herrera MJ, Santana-Sagredo F. Nuevos fechados del sitio Tarapacá-40: recientes análisis y reflexiones sobre un cementerio clave del período Formativo del norte de Chile y Andes Centro Sur (1110 a.C.–660 d.C). Ñawpa Pacha. 2015;35(1):57–89. doi: 10.1179/0077629715z.00000000024

59. Santana-Sagredo, Schulting R, Lee-Thorp J, Agüero C, Uribe M, Lemp C. Paired Radiocarbon Dating on Human Samples and Camelid Fibers and Textiles from Northern Chile: The Case of Pica 8 (Tarapacá). Radiocarbon. 2017;59(04):1195–213. doi: 10.1017/rdc.2017.36

60. Santana-Sagredo F, Lee-Thorp JA, Schulting R, Uribe M. Isotopic evidence for divergent diets and mobility patterns in the Atacama Desert, northern Chile, during the Late Intermediate Period (AD 900–1450). Am J Phys Anthropol. 2015;156(3):374–87. Epub 2014/11/12. doi: 10.1002/ajpa.22663 25385676.

61. Carnese FR, Mendisco F, Keyser C, Dejean CB, Dugoujon JM, Bravi CM, et al. Paleogenetical study of pre-Columbian samples from Pampa Grande (Salta, Argentina). Am J Phys Anthropol. 2010;141(3):452–62. Epub 2009/11/18. doi: 10.1002/ajpa.21165 19918991.

62. Baffi E, Torres MF, Cocilovo J. De la población prehispanica Las Pirguas (Salta, Argentina). Un enfoque integral. Revista Argentina de Antropología Biológica. 1996;1(1):204–18.

63. Perez SI, Monteiro LR. Nonrandom factors in modern human morphological diversification: a study of craniofacial variation in southern South american populations. Evolution. 2009;63(4):978–93. Epub 2008/12/06. doi: 10.1111/j.1558-5646.2008.00539.x 19055678.

64. Gonzalez PN, Perez SI, Bernal V. Ontogenetic allometry and cranial shape diversification among human populations from South America. Anat Rec (Hoboken). 2011;294(11):1864–74. Epub 2011/10/01. doi: 10.1002/ar.21454 21957064.

65. Sardi ML, Rozzi FR, González‐José R, Pucciarelli HM. South Amerindian craniofacial morphology: diversity and implications for Amerindian evolution. American Journal of Physical Anthropology: The Official Publication of the American Association of Physical Anthropologists. 2005;128(4):747–56. doi: 10.1002/ajpa.20235 16044464

66. Del Papa M. La estructura y dinámica del poblamiento humano de Pampa y Patagonia continental durante el Holoceno tardío: un análisis de rasgos epigenéticos craneofaciales.: Universidad Nacional de La Plata; 2013.

67. Abarca V. Efectos de la nutrición sobre el Dimorfismo Sexual expresado en la Estatura (SSD) de una muestra de población Chilena Subactual. Santiago, Chile: Universidad de Chile; 2011.

68. Retamal R, Pacheco A, Uribe M. Perfil osteobiográfico del Cementerio Pica 8: Paleopatología y modos de vida (Períodos Intermedio Tardío, región de Tarapacá, Chile). 2006.

69. Toro-Ibacache V. A finite element study of the human cranium; The impact of morphological variation on biting performance. York: University of York; 2013.

70. Buikstra JE, Ubelaker D. Standards for data collection from human skeletal remains. Fayetteville, Arkansas: Arkansas archeological survey research series no 44.; 1994.

71. Eyquem A. Efecto de la intensidad masticatoria en la forma craneal en poblaciones arqueológicas y modernas de Chile y Argentina Universidad de Chile; 2018.

72. Gilbert CC. Phylogenetic analysis of the African papionin basicranium using 3-D geometric morphometrics: The need for improved methods to account for allometric effects. American Journal of Physical Anthropology. 2011;144(1):60–71. doi: 10.1002/ajpa.21370 20721940

73. Hammer Ø, Harper DAT, Rya PD. PAST: Paleontological Statistics Software Package for Education and Dara Analysis. Palaeontologia Electronica. 2011;4(1).

74. Klingenberg CP. MorphoJ: an integrated software package for geometric morphometrics. Mol Ecol Resour. 2011;11(2):353–7. Epub 2011/03/25. doi: 10.1111/j.1755-0998.2010.02924.x 21429143.

75. Anderson MJ. A new method for non-parametric multivariate analysis of variance. Austral Ecology. 2001;26(1):32–46. doi: 10.1111/j.1442-9993.2001.01070.pp.x

76. Adams DC, Collyer ML. On the comparison of the strength of morphological integration across morphometric datasets. Evolution. 2016;70(11):2623–31. doi: 10.1111/evo.13045 27592864

77. von Cramon-Taubadel N. Evolutionary insights into global patterns of human cranial diversity: population history, climatic and dietary effects. J Anthropol Sci. 2014;92:43–77. Epub 2013/09/17. doi: 10.4436/jass.91010 24038629.

78. Menendez L, Bernal V, Novellino P, Perez SI. Effect of bite force and diet composition on craniofacial diversification of Southern South American human populations. Am J Phys Anthropol. 2014;155(1):114–27. Epub 2014/07/06. doi: 10.1002/ajpa.22560 24985052.

79. Fuentes M, Pulgar I, Gallo C, Bortolini MC, Canizales-Quinteros S, Bedoya G, et al. Geografía génica de Chile. Distribución regional de los aportes genéticos americanos, europeos y africanos. Rev Med Chil. 2014;142(3):281–9. Epub 2014/07/24. doi: 10.4067/S0034-98872014000300001 25052264.

80. Noback ML, Harvati K. The contribution of subsistence to global human cranial variation. Journal of Human Evolution. 2015;80:34–50. doi: 10.1016/j.jhevol.2014.11.005 25661439

81. Toro‐Ibacache V, O'Higgins P. The Effect of Varying Jaw‐elevator Muscle Forces on a Finite Element Model of a Human Cranium. The Anatomical Record. 2016;299(7):828–39. doi: 10.1002/ar.23358 27111484

82. Bastir M. A systems-model for the morphological analysis of integration and modularity in human craniofacial Journal of Anthropol Science. 2008;34(1):77–85.

83. Betti L, Balloux F, Hanihara T, Manica A. The relative role of drift and selection in shaping the human skull. American Journal of Physical Anthropology: The Official Publication of the American Association of Physical Anthropologists. 2010;141(1):76–82. doi: 10.1002/ajpa.21115 19582777

84. Katz DC, Grote MN, Weaver TD. Changes in human skull morphology across the agricultural transition are consistent with softer diets in preindustrial farming groups. Proc Natl Acad Sci U S A. 2017;114(34):9050–5. Epub 2017/07/26. doi: 10.1073/pnas.1702586114 28739900; PubMed Central PMCID: PMC5576786.


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