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生物学 1915

孟德尔遗传的机制

T·H·摩尔根、A·H·斯特蒂文特、H·J·穆勒与 C·B·布里奇斯

基因是实在的点,沿染色体排成一线。

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In depth · the introduction

孟德尔有一些看不见的「因子」,它们服从着工整的比例。摩尔根的果蝇却显示:这些因子是实在的、物理的东西——沿染色体排成一线,你甚至能给它们画出一张地图。

核心想法

在孟德尔之后的几十年里,没人知道他那些遗传「因子」究竟住在哪里。摩尔根的实验室,靠繁育数以百万计的果蝇,把它们钉在了染色体上——那是细胞所携带的、线状的小体。每一个因子(如今我们说基因)都搭在某一条染色体的某个确定位置上。

决定性的窍门在于:同一条染色体上的基因,倾向于一同被遗传(这叫「连锁」);可染色体有时会交换片段(这叫「交换」),从而把它们分开。两个基因坐得越近,就越少被分开。于是,只要数一数两个性状在后代中分开的频率,你就能量出它们的基因之间的距离——并把每一个基因,按次序,排上一张地图。

它是如何诞生的

托马斯·亨特·摩尔根起初是个怀疑论者——他既怀疑孟德尔定律,也怀疑染色体承载遗传这一说法。然而约在 1910 年,一只白眼的雄性果蝇,出现在他哥伦比亚大学那间逼仄的「果蝇室」里,而它那奇特的遗传方式,径直指向了 X 染色体。果蝇不断给出答案,摩尔根于是改了主意。

作图上的突破,来自一位十九岁的本科生——阿尔弗雷德·斯特蒂文特。1911 年的一个夜晚,他意识到交换的数字可以化作距离,便熬夜画出了第一张基因图。卡尔文·布里奇斯钉下了细胞学的证明;赫尔曼·穆勒磨利了理论。他们四人,把这些工作汇成了 1915 年的这本书。

它为何重要

正是这本书,把遗传从一件只能描述的事,变成了一件能测量、能预言的事。「基因」成了一个有坐标的位置。就这一个想法——靠性状重组的频率给基因作图——绘出了我们自身基因组的第一批图谱,并在我们还无法逐个字母地读取 DNA 之前,就帮人们追查到了诸如囊性纤维化这类疾病背后的基因。摩尔根因此荣获 1933 年的诺贝尔奖。

一个可以想象的画面

想象有两枚小坠子,穿在同一根绳子上。时不时地,这根绳子会被剪断一次,再与它的搭档绳子接起来,把断口之外的部分整段互换。如果两枚坠子相距甚远,剪口就很可能落在它们之间,于是它们常常被分开。如果它们几乎贴在一起,剪口便很少落在中间,于是它们几乎总是待在一起。数一数每一对被分开的频率,你就量出了绳子上的间隔——基因图,正是这样画出来的。

一条可交互的果蝇 X 染色体:五个性连锁因子在标尺上排成一线,上方一对同源染色体会在你所选的两个基因之间演示一次交换。选定基因座 A 与 B,读数便给出它们的图距,以及交换把它们拆开的几率——基因靠得近则几率小,离得远则几率大。

它的位置

孟德尔(1865 年)给出了抽象的规则;萨顿与博韦里(1902–1903 年)猜到了染色体在承载这些规则;而这本书,把猜想变成了一张测量出来的地图。这条线索往后延伸到埃弗里(1944 年)与沃森—克里克(1953 年),他们揭示出基因的化学本性是 DNA——但摩尔根的果蝇,早已为基因定下了地址。此后的每一张基因组图谱,包括人类基因组计划,都是这些果蝇图表的后裔。

The original document
Original source text

序言——遗传的问题

Morgan · Sturtevant · Muller · Bridges · The Mechanism of Mendelian Heredity · Henry Holt & Co., 1915 · Preface
From ancient times heredity has been looked upon as one of the central problems of biological philosophy.
The authors set out to show that the abstract Mendelian factors are carried by the chromosomes, and that the behaviour of the chromosomes in the germ-cells accounts, point for point, for the numerical results of breeding experiments.

连锁与交换(第三章)

Chapter III · Linkage
When two factors enter a cross in the same chromosome they tend to be inherited together, rather than to assort independently as Mendel's law of free assortment would require.
The process of interchange between chromosomes is called crossing over; the tendency of factors to stay together is called linkage.
The strength of the linkage differs from pair to pair: yellow and white cross over in about 1 per cent. of cases, white and miniature in about 33 per cent., white and bar in about 44 per cent. Factors that are seldom separated must lie close together; factors often separated must lie far apart.

诸因子的线性排列

Chapter III · The linear arrangement of factors shown by linkage relations
If the factors are arranged in a line along the chromosome, the chance of a break falling between any two of them is proportional to the distance that separates them. The percentage of crossing over therefore measures that distance, and from it the factors can be plotted, in order and to scale, upon a map.
Sturtevant's first such map (1913) placed five sex-linked factors of the fly upon a single line; the maps in this book extend the method, and the order on the map is the order in which the factors lie in the chromosome.

因子假说(第九章)

Chapter IX · The factorial hypothesis
The factor is treated as a definite thing, located at a definite point in a particular chromosome, transmitted by the chromosome from cell to cell and from parent to offspring, and capable, on rare occasions, of changing into a new form (a mutation) that is thereafter inherited in the same orderly way.
Columbia University · New York · 1915