进化从未停止:一项颠覆性研究如何重写我们对自身历史的认知
科学界长期认为,自农业文明以来,自然选择对人类的影响已微乎其微。然而,一项发表于《自然》杂志的研究利用新的纵向分析方法,发现了过去一万年间数百个基因位点经历了强烈的选择,其规模是此前认知的二十倍。这一发现如同在平静的湖面投下巨石:它证明进化从未离场,只是我们未曾看清。更关键的是,许多被选择的基因会随着环境变化而经历“逆转”,这对当下兴起的基于多基因评分的胚胎选择等技术,提出了根本性的伦理与科学质疑。
核心观点:《自然》最新研究表明,过去一万年间人类经历了数百次强自然选择,这彻底颠覆了“近期人类进化近乎停滞”的传统观点,不仅重塑了我们对自身生物性的理解,更对基于现代基因数据的医疗、优生学决策发出了深刻的警示:我们今天所珍视的“优势”基因,可能只是环境压力下的临时方案。
在流行文化和许多科学叙述中,有一个根深蒂固的印象:自从人类进入农业社会,建造城市,创造文化以来,我们便在很大程度上“逃脱”了自然选择的严酷法则。文明为我们提供了缓冲,医学延长了寿命,技术改变了环境,似乎生物进化在最近的一万年里已经放缓至近乎停滞,只剩下如乳糖耐受等少数几个广为人知的例子。然而,最近发表在《自然》杂志上的一项研究,以极其有力的证据,彻底粉碎了这一迷思。大卫·赖希团队的研究表明,在过去的万年间,人类基因组中发生了数百次强烈的自然选择,其信号强度是此前研究发现的二十倍之多。这不仅仅是一个数字的修正,它是一场范式的地震,迫使我们重新思考:我们是谁,我们从何而来,以及,我们将走向何方。
这项研究的颠覆性,首先源于方法论的创新。以往寻找自然选择证据的研究,多采用“横截面”方法:比较不同现代人群的基因频率差异,看其是否超出了由遗传漂变和迁移所能解释的范围。这种方法大多得出结论:人群结构(即祖先源流的不同)是造成差异的主因。而新研究采用了“纵向”视角,将古代DNA样本所处的具体时间点作为一个关键变量纳入分析模型。正是这一改变,极大地提高了探测选择信号的“分辨率”和“灵敏度”。研究者发现,许多选择并非作用于全新的突变,使其频率一路飙升(传统“选择性清除”模型),而是作用于早已存在的基因变异上。这些变异会因短暂的环境压力而被“选中”频率上升,一旦压力消失或其带来的副作用(代价)凸显,又会被“净化”选择所淘汰,频率回落。一个典型案例是TYK2基因的一个变异:它因能增强免疫力、抵御结核病而被选择保留了数千年,随后随着结核病流行度的下降,其导致自身免疫性疾病的风险代价占据上风,该变异的频率便被逐渐降低。这种“潮汐式”的选择模式,是横截面分析方法难以捕捉的,因为它留下的频率变化轨迹更为复杂和微妙。
这一发现带来的直接冲击,是重塑了我们对自身近代生物史的理解。人类并未在文明包裹下停止进化。相反,我们一直在适应着自身创造出的新环境:新的饮食结构、新的聚居模式、新的病原体暴露、新的社会结构带来的选择压力。农业的发明、城市的兴起、贸易路线的开辟、大规模人口的迁徙与混合,所有这些文化事件,都在我们的基因组上刻下了深刻的、动态的印记。进化的引擎从未熄火,它只是换了一种我们之前未曾读懂的工作方式。这项研究目前主要基于欧洲人群的古DNA数据,可以想见,当将其分析方法推广到南亚、东亚、非洲等拥有更复杂人口历史和多样化环境的人群时,必将揭示出更多令人惊叹的进化故事,进一步丰富我们对“人类”这一物种适应性的认知。
然而,这项研究的启示远不止于对人类过去的重新解读,它更像一道强烈的探照灯,照亮了当下某些科技实践所蕴含的巨大风险与认知盲区。研究指出,基于现代大规模全基因组关联分析(GWAS)构建的多基因评分显示,一些性状在近期经历了多基因选择——即许多具有微小效应的基因位点被同时向某个方向推动。例如,与认知能力相关的基因似乎经历了正向选择,而与精神分裂症、体脂率相关的基因则经历了负向选择。这听起来似乎验证了某些“优生”想象的合理性。但论文作者立即提出了一个至关重要的警告:GWAS所测量的性状,完全是在工业化、现代医疗条件下的当代环境中定义的。这些性状与数千年乃至数百年前古人生存繁衍所面临的实际选择压力,可能截然不同。我们今天认为的“好”基因(比如与更高认知测试得分相关),在古代环境中未必带来生存优势,甚至可能因为消耗更多能量等代价而处于劣势。反之亦然。
这一警告对于正处在萌芽状态的、基于多基因评分的胚胎选择(或称“生殖细胞基因编辑”的某种温和形式)不啻为一记当头棒喝。一些公司或家庭可能幻想通过筛选胚胎,让后代在智力、身高、健康风险上获得“最佳”基因组合。然而,古DNA记录清晰地告诉我们,基因的“利弊”并非永恒不变的属性,而是高度依赖于环境背景的。一个在今天看来完美平衡的基因组合,如果被固定下来并遗传下去,当未来环境发生不可预测的变化(新的疫情、气候变化、社会结构剧变)时,完全可能从资产变为负债。人类试图用今天狭窄的、片面的环境视角,去为子孙后代做出永久性的、可遗传的生物学决定,这是一种惊人的傲慢和短视。进化之所以通过自然选择来运作,正是因为它是一个在漫长时空尺度上不断试错、动态调整的过程,以应对永恒变化的环境。用一次性的、基于当下偏好的“人工选择”来替代这一过程,其风险难以估量。
同样,这一发现对现代药物研发和个性化医疗也有深远影响。当我们利用人类遗传学来寻找药物靶点时,我们通常关注的是在当代人群中可见的基因变异与疾病或性状的关联。但新研究提醒我们,一个变异的“益处-危害”比率可能是环境依赖的。某种增加某种疾病风险的变异,可能在历史上的某种特定环境下(如某种病原体肆虐时)曾提供过关键的生存优势。理解这种进化背景,对于全面评估靶点的安全性、预测药物在不同人群中的疗效差异,至关重要。它要求遗传医学具备一种历史的、动态的视角。
最终,这项研究给予我们最深刻的启示,或许是关于“谦卑”。它告诉我们,人类对自身的理解还远未完成。我们不仅对大脑的奥秘、意识的起源知之甚少,甚至对我们自身基因组的近期历史,都刚刚打开一扇新的窗口。在急于运用基因技术“改造”未来之前,我们或许更需要做的是“理解”过去——理解塑造了我们的那股深沉而持续的自然力量。进化从未停止,它就在我们的血液中流动,在我们的历史中书写。承认这一点,意味着承认我们仍然是自然世界的一部分,受其规律的约束。而最好的科技,或许不是试图让我们彻底“超越”或“控制”这些规律,而是学会更智慧地与之共舞。这项古DNA研究,正是为我们提供了这支舞曲更准确的节奏。
参考来源
- RT by @paulg: A new paper in @Nature from David Reich, @aliakbari23 and colleagues breaks the conventional understanding of recent human evolution. The field believed that strong selection in the recent past (~10,000 years) was rare, with few exceptions like the lactase persistence locus. In this paper, the authors challenge that belief, showing that we weren't looking at the problem right.
- Previous studies that looked for evidence of selection using ancient DNA addressed the problem cross-sectionally, asking if allele frequencies differed across populations more than what one would expect based on genetic drift and migration. Most arrived at the conclusion that population structure primarily explained the observed differences. Here, the authors addressed the problem longitudinally, accounting for when ancient individuals lived by explicitly modeling time as a variable in the analysis. It turns out doing it this way dramatically increases power, increasing the number of genome-wide significant selection signals by 20-fold!
- Looking at why accounting for the time variable led to such dramatic changes in results, the authors find that previous studies missed so much because selection often happened not on new variants leading to dramatic sweeps (the conventional model: new variant -> selection -> increase in frequency) but on already existing variants driven by transient environmental pressures. Many of these variants underwent reversals, selected up when a pressure existed, then purged when it disappeared or the trade-off cost became dominant. A great example is the TYK2 variant, where an allele boosting immunity was selected for thousands of years because it protected against TB, then got purged as TB endemicity declined and the autoimmune cost took over.
- The scale of what they found is striking: hundreds of loci showing strong selection in the past 10,000 years with a median selection coefficient of ~0.86%. This number is pretty big in evolutionary terms, meaning allele frequencies have been shifting by ~1% per generation in a consistent direction. Previous selection scans found a maximum of 20 loci, and this one finds hundreds. That isn't an incremental change. It fundamentally reframes our understanding of how common strong selection has been in recent human history.
- Some of the most striking findings come from polygenic selection, where hundreds of small-effect alleles were pushed in the same direction simultaneously. Polygenic scores based on large-scale GWAS of today predict recent negative selection for traits like body fat, waist circumference and schizophrenia, and positive selection for others like cognitive traits. One important caveat is that GWAS phenotypes are measured in industrialized societies today, and how well they capture what was actually being selected in ancient environments is debatable.
- For me personally, these findings have direct implications for drug discovery. When using human genetics to find drug targets, we often fixate on the benefit and risk profiles of variants visible today. But we need to be aware that a variant's benefit:harm ratio might be environmentally contingent, and could reverse when the wrong environment manifests. An evolutionary understanding of a variant's association with traits is therefore essential.
- The same logic applies, perhaps even more urgently, to embryo selection. Selecting embryos based on polygenic traits is humans making permanent, heritable decisions for their offspring with a narrow view of today's environment. The ancient DNA record now shows that cost-benefit landscapes flip over time. So, an embryo carrying man-made selections is carrying those changes into an unpredictable future environment.
- The broader takeaway is that human evolution didn't freeze in the last 10,000 years. We just lacked the tools and datasets to see its movement. The current findings are based on European populations. I am curious to see these analyses extended to other populations too, like South Asian, East Asian and African populations, which might be holding more surprises to blow our minds.
- Akbari et al. Nature 2026
- https://www.nature.com/articles/s41586-026-10358-1 - https://nitter.net/doctorveera/status/2044679999450664967#m
- 【有材曲博士】一种以传统拉面为灵感的脑机接口智能纤维 - https://www.bilibili.com/video/BV1iZd8BnE9o
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