1856年至1863年,奥地利修道士格里高‧约翰‧孟德尔(Dr. Gregor Johann Mendel, 1822—1884)在修道院的花园里进行了豌豆杂交实验。在这八年的时间里,孟德尔观察了豌豆植物的遗传特征,并发现了遗传的基本规律:基因成对出现,决定着生物的功能,且具有不同的优势。基因作为独立的单位,代代相传,这个研究结果后来被称为“孟德尔遗传定律”。²⁰⁴
到了1902年,德国细胞学家西奥多‧海因里希‧博韦里²⁰⁵(Theodor Heinrich Boveri, 1862—1915)和美国遗传学家沃尔特‧萨顿²⁰⁶(Walter S. Sutton, 1877—1916)分别通过各自的研究,独立提出染色体是遗传因子的载体的结论。他们的研究为染色体和遗传因子的关联提供了关键证据。
他们在文章的标题下面用显著大字写道:“蛋白质的大部分演变、变化可能是由于中性突变和遗传漂移。”(Most evolutionary change in proteins may be due to neutral mutations and genetic drift.)文章中还指出:“DNA的所有或大部分变化并不一定都是由于达尔文自然选择的作用。”(It does not necessarily follow that all, or most, evolutionary change in DNA is due to the action of Darwinian natural selection.)
1983年,木村总结了多名科学家对中性理论的研究贡献,包括他自己以及他最密切的合作者太田朋子(Tomoko Ohta)等人的研究成果,出版了《分子演化的中性理论》(The Neutral Theory of Molecular Evolution)一书和后续论文²¹⁸。现在,这本书已被看作经典之作,它确立了中性理论作为分子演化的范式。这里的分子演化,实质上就是“分子变异”。
后来木村的弟子兼同事太田朋子(Tomoko Ohta)又提出了近中性理论(nearly neutral theory of molecular evolution),阐述轻微有害的基因突变可以和中性突变一样在种群中扩散²¹⁹。考虑到许多突变通常是中性的或稍微有害的,近中性理论显著提高了中性理论可以解释的突变范围。
这篇论文由美国加州大学戴维斯分校和德国马克斯‧普朗克发育生物学研究所(Max Planck Institute for Developmental Biology in Germany)合作完成。这两家机构都是行业中有影响力的科研机构。为了弄清楚基因突变背后的深层规律,科学家花了3年时间,研究了拟南芥的超过100万个基因突变。
他们研究的是一种在真核基因组中很普遍的“拷贝数变异”(copy number variation,简称CNV),这种变异长期以来被认为是随机发生的。DNA经常会包含多个核苷酸序列甚至整个基因的拷贝。例如,人类正常染色体拷贝数是2,有些染色体区域拷贝数则变成1或3,即该区域就发生了“拷贝数变异”,这与许多人类疾病有关,尤其是癌症的CNV 促发肿瘤和对化疗的耐药性。
比如孟德尔、摩根等划时代的科学家,当他们发现遗传学的规律之后,其实原本是非常反对达尔文进化论的,因为达尔文在提出进化论时,根本不知道有遗传基因的概念。摩根曾经写过两本重要著作,在第一本《进化与适应》(Evolution and Adaptation)(1903)中,他强烈批评了达尔文理论;第二本书是《对进化论的批判》(A Critique of the Theory of Evolution)(1916)。但是后来摩根也不得不被迫妥协并放弃自己原来的观点。²²⁸
203. Britannica, The Editors of Encyclopaedia. “Walther Flemming”. Encyclopedia Britannica, 17 Apr. 2023, https://tinyurl.com/47wcut2s. Accessed 12 July 2023.
204. Miko, I. 2008 Gregor Mendel and the principles of inheritance. Nature Education 1(1):134.
https://tinyurl.com/46pupa6r
205. Britannica, The Editors of Encyclopaedia. “Theodor Heinrich Boveri”. Encyclopedia Britannica, 11 Oct. 2022, https://www.britannica.com/biography/Theodor-Heinrich-Boveri. Accessed 13 July 2023.
206. Britannica, The Editors of Encyclopaedia. “Walter Sutton”. Encyclopedia Britannica, 1 Jan. 2023, https://www.britannica.com/biography/Walter-Sutton. Accessed 13 July 2023.
208. WATSON, J., CRICK, F. Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid. Nature 171, 737–738 (1953).
https://tinyurl.com/mr3s3638
209. Chen, J., Glémin, S., & Lascoux, M. (2020). From Drift to Draft: How Much Do Beneficial Mutations Actually Contribute to Predictions of Ohta’s Slightly Deleterious Model of Molecular Evolution? Genetics, 214(4), 1005-1018.
https://doi.org/10.1534/genetics.119.302869
210. Rosen G. (1977). Rudolf Virchow and Neanderthal man. The American journal of surgical pathology, 1(2), 183–187.
https://doi.org/10.1097/00000478-197706000-00012
211. Good, B. H., McDonald, M. J., Barrick, J. E., Lenski, R. E., & Desai, M. M. (2017). The Dynamics of Molecular Evolution Over 60,000 Generations. Nature, 551(7678), 45.
https://doi.org/10.1038/nature24287
212. Kronenberg, Z. N., Fiddes, I. T., Gordon, D., Murali, S., Cantsilieris, S., Meyerson, O. S., Underwood, J. G., Nelson, B. J., P. Chaisson, M. J., Dougherty, M. L., Munson, K. M., Hastie, A. R., Diekhans, M., Hormozdiari, F., Lorusso, N., Hoekzema, K., Qiu, R., Clark, K., Raja, A., …Eichler, E. E. (2018). High-resolution comparative analysis of great ape genomes. Science.
https://doi.org/aar6343
213. Pray, L. (2008) DNA Replication and Causes of Mutation. Nature Education 1(1):214.
https://tinyurl.com/8j73phu8
214. Fu, X., & Huai, H. (2003). Estimating mutation rate: How to count mutations? Genetics, 164(2), 797-805.
https://doi.org/10.1093/genetics/164.2.797
215. Woodruff, R. C., Huai, H., & Thompson, J. N., Jr (1996). Clusters of identical new mutation in the evolutionary landscape. Genetica, 98(2), 149–160.
https://doi.org/10.1007/BF00121363
216. KIMURA, M. Evolutionary Rate at the Molecular Level. Nature 217, 624–626 (1968).
https://doi.org/10.1038/217624a0
217. King, J. L., & Jukes, T. H. (1969). Non-Darwinian evolution. Science (New York, N.Y.), 164(3881), 788–798.
https://doi.org/10.1126/science.164.3881.788
218. Kimura M. (1991). The neutral theory of molecular evolution: a review of recent evidence. Idengaku zasshi, 66(4), 367–386.
https://doi.org/10.1266/jjg.66.367
219. OHTA, T. Slightly Deleterious Mutant Substitutions in Evolution. Nature 246, 96–98 (1973).
https://doi.org/10.1038/246096a0
220. Jensen, J. D., Payseur, B. A., Stephan, W., Aquadro, C. F., Lynch, M., Charlesworth, D., & Charlesworth, B. (2019). The importance of the Neutral Theory in 1968 and 50 years on: A response to Kern and Hahn 2018. Evolution; international journal of organic evolution, 73(1), 111–114.
https://doi.org/10.1111/evo.13650
221. Cui, R., Medeiros, T., Willemsen, D., Iasi, L. N. M., Collier, G. E., Graef, M., Reichard, M., & Valenzano, D. R. (2019). Relaxed Selection Limits Lifespan by Increasing Mutation Load. Cell, 178(2), 385–399.e20.
https://tinyurl.com/39c8cxjs
222. Monroe, J.G., Srikant, T., Carbonell-Bejerano, P. et al. Mutation bias reflects natural selection in Arabidopsis thaliana. Nature 602, 101–105 (2022).
https://doi.org/10.1038/s41586-021-04269-6
223. Emily C. Dooley January 12, 2022. Study Challenges Evolutionary Theory That DNA Mutations Are Random. Findings Could Lead to Advances in Plant Breeding, Human Genetics. https://tinyurl.com/ps9kmub8. Accessed on 19 June 2023.
224. Domingues, V. (2023). Mutations are not random. Nature Ecology & Evolution, 7(1), 5.
https://doi.org/10.1038/s41559-022-01959-w
225. Hull RM, Cruz C, Jack CV, Houseley J (2017) Environmental change drives accelerated adaptation through stimulated copy number variation. PLoS Biol 15(6): e2001333.
https://doi.org/10.1371/journal.pbio.2001333
226. King, J. L., & Jukes, T. H. (1969). Non-Darwinian evolution. Science (New York, N.Y.), 164(3881), 788–798.
https://doi.org/10.1126/science.164.3881.788
227. Palazzo, A. F., & Kejiou, N. S. (2022). Non-Darwinian Molecular Biology. Frontiers in Genetics, 13.
https://doi.org/10.3389/fgene.2022.831068