1856年至1863年,奧地利修道士格里高‧約翰‧孟德爾(Dr. Gregor Johann Mendel, 1822—1884)在修道院的花園裏進行了豌豆雜交實驗。在這八年的時間裏,孟德爾觀察了豌豆植物的遺傳特徵,並發現了遺傳的基本規律:基因成對出現,決定着生物的功能,且具有不同的優勢。基因作爲獨立的單位,代代相傳,這個研究結果後來被稱爲「孟德爾遺傳定律」。²⁰⁴
到了1902年,德國細胞學家西奧多‧海因裏希‧博韋裏²⁰⁵(Theodor Heinrich Boveri, 1862—1915)和美國遺傳學家沃爾特‧薩頓²⁰⁶(Walter S. Sutton, 1877—1916)分別通過各自的研究,獨立提出染色體是遺傳因子的載體的結論。他們的研究爲染色體和遺傳因子的關聯提供了關鍵證據。
他們在文章的標題下面用顯著大字寫道:「蛋白質的大部分演變、變化可能是由於中性突變和遺傳漂移。」(Most evolutionary change in proteins may be due to neutral mutations and genetic drift.)文章中還指出:「DNA的所有或大部分變化並不一定都是由於達爾文自然選擇的作用。」(It does not necessarily follow that all, or most, evolutionary change in DNA is due to the action of Darwinian natural selection.)
1983年,木村總結了多名科學家對中性理論的研究貢獻,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《分子演化的中性理論》(The Neutral Theory of Molecular Evolution)一書和後續論文²¹⁸。現在,這本書已被看作經典之作,它確立了中性理論作爲分子演化的範式。這裏的分子演化,實質上就是「分子變異」。
後來木村的弟子兼同事太田朋子(Tomoko Ohta)又提出了近中性理論(nearly neutral theory of molecular evolution),闡述輕微有害的基因突變可以和中性突變一樣在種羣中擴散²¹⁹。考慮到許多突變通常是中性的或稍微有害的,近中性理論顯著提高了中性理論可以解釋的突變範圍。
這篇論文由美國加州大學戴維斯分校和德國馬克斯‧普朗克發育生物學研究所(Max Planck Institute for Developmental Biology in Germany)合作完成。這兩家機構都是行業中有影響力的科研機構。爲了弄清楚基因突變背後的深層規律,科學家花了3年時間,研究了擬南芥的超過100萬個基因突變。
他們研究的是一種在真核基因組中很普遍的「拷貝數變異」(copy number variation,簡稱CNV),這種變異長期以來被認爲是隨機發生的。DNA經常會包含多個核苷酸序列甚至整個基因的拷貝。例如,人類正常染色體拷貝數是2,有些染色體區域拷貝數則變成1或3,即該區域就發生了「拷貝數變異」,這與許多人類疾病有關,尤其是癌症的CNV 促發腫瘤和對化療的耐藥性。
比如孟德爾、摩根等劃時代的科學家,當他們發現遺傳學的規律之後,其實原本是非常反對達爾文進化論的,因爲達爾文在提出進化論時,根本不知道有遺傳基因的概念。摩根曾經寫過兩本重要著作,在第一本《進化與適應》(Evolution and Adaptation)(1903)中,他強烈批評了達爾文理論;第二本書是《對進化論的批判》(A Critique of the Theory of Evolution)(1916)。但是後來摩根也不得不被迫妥協並放棄自己原來的觀點。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