Chapter 32 Chapter 17 The Growth of Mendelian Genetics-2
17.6 Sex Determination
The question of what determines a baby's sex has been speculated at least since ancient Greece.We now know that the earlier theories were wrong. (See Lcsky, 1950; Stubbe, 1965 for details).Some say it is determined by the left or right side of the uterus where the embryo is, some say it is determined by the sperm coming from the main testicle or the right testicle, others say it is determined by the number of sperm, the "heat" of the male or female fluid, etc. .What these theories have in common (and decisively) is that sex is not determined by genetic blocks but purely by environmental factors that coincide with the act of fertilization.
Although the genetic basis of sex was discovered later (after 1900), certain eminent embryologists and endocrinologists persisted in environmental determinism for decades.I think that the sex of some creatures is indeed not determined by genetics.
Some bright Mendelians did not ignore the fact that the 1:1 sex (sex) ratio (value) and the ratio obtained by crossing a heterozygous (Aa) with a homozygous recessive (aa) exactly the same.Mendel already mentioned this in his letter to Negri on September 17, 1870.Other scholars (strasburger and Kessel) also put forward the same view after 1900, but Currens first presented experimental evidence that half of the pollen of the dioecious plant Bryonia (Bryonia) determines the male plant, The other half is female-determining, while all eggs are gender-neutral.In this case the male is heterozygous, heterogametic in Wilson's (1910) term, and the female homogametic.It was later shown that females of birds and Lepidoptera are heterogametic, while males of mammals (including humans) and dipteran insects (including Drosophila) are also heterogametic.So, is it possible that sex is linked to a particular chromosome?Later, a large amount of evidence gradually accumulated to confirm this assumption.
From the beginning of chromosome research, it has been observed that all chromosomes are not necessarily identical in appearance.
In 1891, Henkins found that half of the sperm had 11 chromosomes during the meiosis of the insect Pyrrhocoris, and the other half of the sperm had an extra darkly stained object in addition to the 11 chromosomes.Since he was not sure if it was a chromosome, Henking indicated it with the letter X. Henking does not connect the X-body with sex.
During the ensuing decade, more cases were found that indicated that there were indeed such extra chromosomes, or that a pair of chromosomes differed from the rest of the chromosome set in size, chromosomal properties, or other characteristics.Having observed that half of the spermatozoa in Hongzhi possessed an X (accessory) chromosome and the other half did not, McClung (1901) reasoned as follows: "We know that the only property which divides the members of a species into two classes It is sex, so I infer that this accessory chromosome is the element that determines the continued development of the germ cells of the embryo and makes the slightly changed egg cell become a highly specialized sperm, "that is to say, these more or less unusual chromosomes are sex chromosomes, which play a role in determining The role of gender.But some details of McClung's conclusion are wrong. Nettie Stevens (1905; see Brush, 1978) and Wilson (EB Wilson, 1905) soon correctly identified the role of sex chromosomes in determining sex.
There are many different patterns of sex determination, sometimes involving multiple sex chromosomes, sometimes males are heterozygous and in other cases heterozygous females.All these details can be found in any textbook of genetics or cytology (see Wilson, 1925; White, 1973).Importantly, it was demonstrated that a phenotypic trait, sex, is associated with a particular chromosome.
This is the first conclusive demonstration of such a link.Most genetic research in the ensuing years was devoted to demonstrating the relationship between other traits and the sex chromosomes or other chromosomes (autosomes or common chromosomes).This type of research enriched the theory of chromosomal inheritance, and its leader was Morgan.Their research finally rejected the theory that all chromosomes are the same in hereditary function.This theory has been very popular after 1900, although it has been found that the size of the chromosomes of many species is extremely inconsistent. The reason why some biologists in the 1880s and 1890s insisted on this (to us) implausible theory is probably because in some species all chromosomes are indeed very similar.
After the individuality (independence) of chromosomes has been demonstrated and at least one trait (sex) has been found to be associated with a particular chromosome, geneticists can concentrate on exploring deeper questions about chromosomes and traits, or with Johnson's words refer more specifically to the question of the relationship between chromosomes and genes.Do chromosomes control a whole set of traits as a whole (say like a command center for a newly opened battlefield)?Are individual genes located in specific parts of the chromosome?How are different genes related to each other if they are on the same chromosome or on different chromosomes?These questions were answered in a relatively short period of time (essentially 10 years from 1905-1915, in fact mostly from 1910 to 1915), by ingenious genetic experiments and Obtained by continuous examination with cytological evidence.These experiments always start with fairly simple Mendelian phenomena.
17.7 Morgan and his Drosophila Laboratory
Morgan began breeding fruit flies in 1909.He was impressed by de Vry's evening primrose mutation and tried, without success, to induce mutations in his flies with different chemicals, different temperature treatments, calcium and X-ray radiation.Yet in his Pedigreed cultures there was a white-eyed male that appeared in the normal population of red-eyed flies.
This simple fact, the emergence of a single anomalous individual in a laboratory culture, has sparked a veritable avalanche of research.The first question raised is how this "white-eyed" trait arises.
After mating this rare white-eyed male fruit fly with the same generation of female fruit flies, Morgan found that although the F1 generation was all red-eyed, the white-eyed male fly appeared in the F2 generation, which means that the genetic factor of white eyes is recessive, and it must be Produced by a sudden change in the red eye gene.Morgan, who had visited de Vrij's laboratory in the Netherlands a few years earlier, adopted de Vrij's term "mutation" for the origin of the new allele.Due to de Vry's theory of evolutionary mutation and the chromosomal nature of evening primrose mutations, the transfer of this term had unfavorable consequences, causing a certain amount of intellectual confusion in the ensuing twenty or thirty years (Anen, 1967; Mayr and Provine , 1980).Yet geneticists and evolutionists alike eventually got used to the new meaning Morgan gave to the word "mutation."
Few in the history of biology have worked so closely together with Morgan and his colleagues.It is therefore difficult to determine who should be credited for much of Morgan's lab's work or discoveries.Some historians tend to attribute almost all the credit to his students and colleagues.This is too much.It should be remembered that in the two years since Morgan published his first paper on Drosophila in July 1910 he published 13 consecutive papers on the discovery and connection of more than 20 sex-linked (sex-linked) mutants in Drosophila. Behavioral articles.Shortly after the discovery of white eyes, two sex-linked recessive mutants were discovered: "wing hypoplasia" and "yellow body color".There is no doubt that Morgan articulated most of the mechanisms of Mendelian inheritance very early on, and these were his own contributions.As Muller (1946) put it: "No matter how much the history of the beginnings of Drosophila research may be rewritten and re-evaluated in the future, Morgan's argument for the phenomenon of crossover and the idea that genes exchange more frequently the farther apart they are Chunlei, whose significance is no less important than the discovery of Mendel's theory, this point must still be recognized." What I want to emphasize here is Morgan's own contribution to the chain and exchange problems alone, because the discussion in the future will focus on Issues rather than individual contributions from everyone in the Drosophila lab.Morgan and his colleagues grew thousands of fruit flies in Columbia University's "Drosophila Chamber."As they scrutinized the flies, they found that new mutations kept popping up.Morgan quickly (191O-1911 winter) selected Alfred H, Sturtevant and Bridges (Calvin B. Bridges) from Columbia University's ungraduated students to work in his laboratory, Later Muller (H.J. Muller) also participated in this research group (he is still studying for a degree under the guidance of Morgan).The close collaboration of this group is an anecdote in biology; "Seldom in the past has there been such an exciting atmosphere and such sustained enthusiasm in a scientific laboratory. This is mainly due to the attitude of Morgan himself, who will be enthusiastic and critical. A fusion of spirits, generosity, open-mindedness and a sense of humour”
(Stuvtevant, 1959; 1965a).
In just a few years all major aspects of transmission genetics were elucidated by Morgan and his group.Whatever Bateson, De Vry, Currens, Kessel (Castle) and other early Mendelians did not find the right answer (indeed, did not ask the right question) was done brilliantly by Morgan's group up.An important reason for this is that although Morgan was born as an embryologist, he put aside the problems of gene physiology and ontogeny, and devoted himself cautiously to the transmission of genetics.He did not speculate on the laws of heredity but inquired into facts and the simplest possible explanations for those facts.He is a thorough empiricist.
Mendel was well aware that phenotypic traits occur in groups and, in the traits he chose, in pairs. Research work after 1900 has confirmed that the material basis corresponding to a certain manifestation can have alternative manifestations or expressions.Translated literally into Greek, these alternative determinants are the "relative genes"
(allelomorphs, Bateson's term) or alleles (alleies).The discovery of such alternative determinants of some phenotypic traits in Mendelian inheritance can provide a completely new explanation for the cause of variation.This suggests that smooth versus wrinkled peas, yellow and green, or some other similar pair of traits may have the same material basis.The traits expressed by alleles should preferably be two translations of the same genetic material.
In 1904, Cuenot of France found that a group of traits may have more than two alleles in the house mouse; for example, in the special case of the house mouse, its skin color may be gray, yellow, or black.Bateson, Kessel, Shull, Morgan, and other geneticists later discovered such multiple alleles.The human ABO blood type is a well-known example. Sturtevant (1913) first explained the phenomenon of multiple alleles, attributing it to various alternative states of the same gene (locus).This completely negates the presence or absence of Bateson's gene effect theory (Presence-absence tbeory).In some special cases, a gene has more than 50 alleles, such as blood group genes of cattle, some compatibility genes of plants, and tissue compatibility genes of vertebrates.Consistent with Mendel's laws, there is always only a single allele in a given gamete, but at fertilization it can combine with any of the many different alleles present in the gene pool of the population.Later in the history of genetics it was also found that genes behave like alleles in some crosses but not in others (pseudoallelism). Lewis and Green's analysis of such situations led to a step forward in understanding the nature of genes (see below).
Morgan's team's work on the white eye gene in Drosophila, as well as other mutants in Drosophila, definitively demonstrated that one gene can mutate into another allele, which in turn can mutate into a third and fourth allele .It is also worth noting that these mutational steps are reversible, and white-eyed Drosophila occasionally produces red-eyed offspring.Perhaps the most important finding was that once a new allele of a gene has been created, that new allele remains unchanged unless a new mutation occurs in one of its descendants.The gene is thus characterized by its almost complete stability.The discovery of genetic mutations is not a regression to soft inheritance, on the contrary, it confirms that the genetic material is largely fixed.It can be said that this is a decisive sign of hard inheritance, that is, despite the inherent stability of genetic material, it has the mutation capacity allowed by evolution.
It was soon established that all other living things can mutate, from humans and other mammals to the simplest animals, plants of all kinds, and even microbes.In fact the study of mutations from 1920 until 1950 seemed the most promising line of research to elucidate the nature of genetic material.The study of the mutation process also raises some difficult questions.What exactly happens to genes when they mutate?Can variation be produced under control conditions (i.e. under experimental conditions)?De Vry mentioned as early as 1904 that "X-rays and radium rays can penetrate biological cells and can be used to modify genetic particles in germ cells" (Blakeslee, 1936).Attempts have been made since 1901 to induce mutations by means of X-rays, radium rays, sudden changes in temperature (temperature shock), or chemicals.Due to various technical deficiencies (heterogeneous substances, small sample size, etc.), no clear results were initially obtained.It was not until 1927 that the research was carried out through Muller's perseverance and ingenuity.
One of Mendel's important discoveries was that "every pair of dissimilar characters in a hybrid (combination) behaves independently of all other differences in the two parental plants" (1866:27).Now we generally call it the law of free assortment of traits.
For example, Mendel crossed a pea line with rounded yellow kernels (both traits are dominant) with another purebred line of pea with wrinkled green kernels (both recessive).The ratio of round soybeans and wrinkled mung beans he collected in several generations is not 3:1.In this special experiment, he collected a total of 556 beans, of which 315 were round yellow, 101 wrinkled yellow, 108 round green, and 32 wrinkled green, with a ratio close to 9:3:3:1.Therefore, the ratio of each pair of traits (round to wrinkled, yellow to green) is 3:1 (round, yellow are dominant), but these two traits are segregated independently of each other.Mendel found that the same was true for the other five pairs of traits he tested, and at one time thought that all traits obeyed this law of free assortment.
If the nucleus were just a pocket filled with pairs of buds, which would separate and distribute independently before gametes formed, Mendel's discovery was so natural that it should not be surprising.However, since the nuclear material is organized into chromosomes, and the chromosomes segregate as a whole during gamete formation, there can be no more independent pairs of traits than the number of chromosomes.Mendel's free assortment of seven traits was consistent with the fact that peas were found much later to have exactly seven pairs of chromosomes (see below). Since the rediscovery of Mendel's laws, more and more cross-breeding experiments have been carried out in these Exceptions to free assemblage have been found experimentally (first by Currens in violets in 1900, others by Bateson's group), however such exceptions are difficult to Explanation.It was not long before Morgan discovered that sex and eye color did not combine freely in the white-eyed fruit fly.When he crossed the F1 flies, the ratio of red eyes to white eyes in the F2 generation was 3:1, but all the white eyes were males, and in all the red-eyed flies the sex ratio was 2:1 (see Figure 2a).In other crosses, the results were even more surprising.For example, when white-eyed female flies were crossed with normal red-eyed males, all female offspring were red-eyed and all male offspring were white-eyed (Fig. 2b).
Fig. 2a The F1 generation male flies of the red-eyed female parent have the female X chromosome as red-eyed.50% of F1 females have F2 males with white eyes due to normal Mendelian segregation
Figure 2b In reciprocal crosses (reciprocal crosses), F1 female flies receive the maternal X chromosome.If the female parent is homozygous recessive white-eyed, all male offspring will be white-eyed, although the male parent is obviously red-eyed, and sex genes and eye color genes are not freely combined.
Based on the above observations, Morgan concluded in 1910 that the eye color factor (mutation from red to white) is coupled to the sex-determining X factor.A year later (1911: 384) he specifically explained this kind of trait coupling phenomenon from the perspective of chromosomes: "What we found was not random segregation in the Mendelian sense, but "factor associations" that are close together on chromosomes. of factors). Cytology provides the mechanism needed for experimental evidence." Other mutations, such as luteal body color and small wings, are also: sex-linked, that is, located on the sex chromosomes.Other trait linkage groups are not related to sex and are apparently on other chromosomes in Drosophila, which are called autosomes or common chromosomes (as distinguished from the sex chromosomes).
De Vry, Collens, Boverly, and Sutton had actually predicted the chain phenomenon theoretically.They reasoned from the individuality and continuity (through the mitotic cycle) of chromosomes.
Bridges (a member of Morgan's group) in 1914 provided a more convincing proof for the theory of chromosomal inheritance.F1 Generations produced equal numbers of heterozygous red-eyed females and white-eyed males.This is determined by the genetic makeup of the two parents, necessarily.
But in Morgan's lab an unusual line of fruit flies emerged that in such a cross experiment had about 4.3 percent of its F1 generation white-eyed females and red-eyed males.The details and explanations of this test are described in detail in classic genetics textbooks and will not be repeated here.Bridges had imagined that the female flies of this strain would have not only two X chromosomes but also a male Y chromosome.This XXY female fruit fly probably arose when an abnormal egg with two XX chromosomes (due to an error in meiosis) was fertilized by a Y sperm.When such an individual with three sex chromosomes (two X, one Y) forms gametes, or these two X chromosomes enter different gametes (eggs), X and XY eggs (actually formed gametes) are formed This is the case in 91.8% of the cases) more or two Xs enter one egg, and Y enters another egg, forming XX and Y eggs (about 8.2%). After normal, X or Y XXX and YY zygotes could not survive and died, but a small number of special red-eyed male flies (XY) and white-eyed female flies (XXy) were produced (see Figure 3). Bridges' idea was later confirmed by cytological observation , which confirms the existence of XXY female flies and XYY male flies in this strain of fruit flies.
Before (Wilson, 1909) and since then, some nondisjunction phenomena have been found, including individuals containing extra autosomes.For example, there are three chromosomes 21 in humans, known as trisomy 21 due to nondisjunction, which is the cause of Downs Syndrome (Downs Syndrome).In many plant species there are individuals who have an extra chromosome (trisomy) or have lost an autosome (monosomy).These individuals survived and were used to study various balancing effects of the same gene.For example, any trisomy of 12 pairs of chromosomes in the genus Datura not only survives but also has a special shape.The same is true for any single monomer of Nicotiana 23 chromosomes.
The significance of Bridges' study is that it provides the first direct evidence that a sex-linked gene is carried on the X chromosome.His conclusion was confirmed again and again later.Since then there has been less reason to object to the chromosome theory, although a few scholars, such as Bateson and Goldschmidt, remain skeptical, and even Morgan is somewhat equivocal.
17.8 Meiosis (Mature Division, Meiosis)
After 1902, although some biologists talked casually about the theory of chromosomal inheritance, its precise meaning was not very clear at that time.Most people refer to Roux's suggestion that the various genetic elements (now should be said genes) be arranged in a straight line on the chromosome.However, this is not the whole problem.Cytologists in the 1870s to 1890s discovered many chromosomal phenomena that were definitely related to heredity. After 1900, these phenomena were systematically studied, especially after 1910 by Morgan's research group, which greatly promoted the development of chromosome theory.
Let's start with the behavior of chromosomes during gamete formation.Both the nucleus of the egg and the sperm are "haploid," meaning they have half the number of chromosomes that a (diploid) somatic cell has.How is the number of chromosomes halved during gamete formation and how does this affect heredity?
Van Beneden (1883) discovered that when an roundworm egg is fertilized, the two chromosomes of the male sperm and the two chromosomes of the egg nucleus unite to form a new nucleus that is zygotic with four chromosomes.The resulting cleavage of this fertilized egg contains four chromosomes each; each cell is "diploid" and has twice as many chromosomes as the gamete.If the number of chromosomes were doubled at each fertilization, the offspring would have twice as many chromosomes as the parents, so each cell would soon have thousands of chromosomes.Clearly, some process must counteract the doubling of chromosome numbers during fertilization. Strasburger (1884) and Weissmann have successively proposed that "meiosis" must be carried out before the formation of gametes.Boverly (1887-1888) also agreed with Weisman's opinion, and later Hertwick made a detailed and correct description of the meiosis process in 1890.
Cytologists discovered that animals undergo two consecutive cell divisions during the formation of gametes, which are very different from normal mitosis, which was later called meiosis or mature division (me1os1s).Exactly what lenization (or rather how chromatin is reduced) occurs during meiosis has been long debated and unresolved.
The only fact that was quickly recognized at that time was that oocytes and spermatocytes (that is, the cells that eventually develop into eggs and sperm) had the same number of chromosomes as ordinary somatic cells, and they were all diploid; The resulting gametes (eggs and sperm) have half the number of chromosomes and are haploid.When the essence of meiosis is fully understood, it is known that the maturation of the nucleus of the egg cell is completely similar to that of the sperm; but at first glance, the maturation processes of these two types of cells are very different, so they will be introduced separately below.
The chromosome set of each nucleus is composed of a pair of homologous chromosomes, one from the father and the other from the mother.During the first meiotic division, the pair of homologous chromosomes are closely attached to each other from the side, and this pairing process is called "synapsis".At first the details of what happened in this pairing process were completely unclear; the two fit together so closely that microscopic analysis could not determine what was going on in the prophase of the first meiotic division.It took almost another 30 years for this process to be fundamentally understood through genetic analysis (see below).What Beverly and Hertwick observed was the separation of chromosomes after cataclysm (condensation phase), just as in normal mitosis.
In the egg cell this division is carried out at the periphery of the egg, a set of daughter chromosomes (daughter chromosomes) are excluded in the form of a single polar body.
The second nuclear division of meiosis is special because only the nucleus divides and the chromosomes do not divide.The result is that half of the chromosomes go to the daughter nucleus and the other half go to another nucleus.In roundworms, the number of chromosomes is thus reduced from four to two.This second division is called the reduction division by Weissmann.One of the two daughter nuclei in the egg cell is excluded as a second polar body.
The same two nuclear fissions also occur during the formation of male gametes, but the difference is that no daughter nuclei are expelled in the form of polar bodies.
Instead, a group of four spermatozoa was formed, which came from the .It is produced by a nucleus in spermatocytes during human meiosis, as pointed out by Hertwick (1890).Since the number of chromosomes does not double in the second meiosis, these four sperm also have half the number of chromosomes of the diploid somatic cells.What I present here is only the final explanation of what happens in meiosis, the details of which are assembled by the discoveries and explanations of VanBeneden, Hertwick, Weismann, and others; Churchill (1970) has The process of understanding the development of this issue has been brilliantly expounded.At first, Hertwick and Weissmann disagreed greatly with each other on interpretations, for two important reasons.Hertwick believed somewhat in fusogenic inheritance, in which the paternal and maternal chromosomes fuse with each other at fertilization, and he believed that after each cell division the chromosomes were dissolved and recomposed of dyed granules before the next round of cell division.In situ, the exclusion of polar bodies is simply a reduction in the amount of dyed material.Weismann, in contrast, argued that the paternal and maternal chromosomes remained separate after fertilization, and that each chromosome remained continuous throughout mitosis, meiosis, and the subsequent quiescent phase.On both issues Weissmann's assumptions turned out to be correct.The most important conclusion to be drawn from the foregoing controversy is that the polar bodies excreted by the egg contain exactly the same amount of chromosomes as those retained in the nucleus of the egg.Thus the division of the nucleus (meiosis) in the formation of female and male gametes is exactly the same, although in females the final result is the formation of one egg and three polar bodies, in males four spermatozoa.Although Hertwick and Weisman openly debated the technical details of cytology, as Churchill (1970) wisely pointed out, the essence was determined by their different positions and concepts.Hertwick represented the physicist camp of physiology, Weissmann represented the morphological particle theory molecular school.
We can also express the cytological content of meiosis in terms of genetics.It is assumed that the formation of a new zygote is the result of the fusion of the paternal and maternal chromosome sets, in which one chromosome with the allele A (from the paternal parent) matches a chromosome with the allele a (from the maternal parent) to produce the zygote Aa .From the first cleavage of this new zygote, the two homologous chromosomes will remain paired, and all somatic cells of the developing organism will be heterozygous for Aa.Only during the second mature division (meiosis) during gamete formation do the two homologous chromosomes separate, forming an equal number of gametes with gene A and gametes with gene a.Which chromosome gets into the daughter cell is purely accidental (see below).Mendel's law of segregation is thus satisfactorily explained by the observed behavior of chromosomes during fertilization and gamete formation.The introduction of meiosis can explain linkage and segregation phenomena very well here, but the problem is not over yet, and it cannot explain the incomplete linkage phenomenon pointed out above.But this can be illustrated by another process in meiosis, crossing over.Meiosis in plants is chromosomally identical to that in animals, but usually occurs at a different stage of the life cycle (before spore formation).
Since the traits of any organism and the genetic factors that determine these traits far exceed the number of chromosomes it contains, some people (Correns, 1902; Sutton, 1903,) thought that each chromosome must carry several (if not many) genes.This was quickly confirmed by Morgan's research team.However, the discovery of linkage groups (each linked to a particular chromosome) raised new questions.If all the genes on a chromosome were tightly linked together, then an organism would have only as many independent genetic units as there are chromosomes it contains.This imposes great constraints on reorganization.De Vry's (1903) study of F2 hybrids concluded that the possible chances of recombination in F2 hybrids were far from consistent with a full linkage view.He therefore proposed an "exchange of units" between paired parental chromosomes during the first prophase of meiosis.As to "how many and which (units will be exchanged) may be purely accidental" (1910: 243), this suggests that exchanges are always mutual exchanges.Boverly also predicted this type of exchange (1904:118).Genetic analysis quickly demonstrated that the linkage of genes on the same chromosome was incomplete.Bateson, Saunders, and Punnett (1905) were the first to conduct such observational studies.In F2 crosses of two varieties of sweet pea (Lathyrus) (different from each other in flower color and pollen grain shape), they neither obtained the expected 9:3:3:1 ratio nor the simple 3:1 ratio , but found 69.5% of double-dominant individuals, 19.3% of double-recessive individuals, and 5.6% of two types of heterozygotes.It is clear that the genes for these two traits are neither freely assortable nor fully linked (with an 11% exception).Bateson had proposed a special hypothesis to explain this phenomenon, but since he did not believe in chromosome theory, he did not consider exchange.
It used to be said that it was an oddity that Mendel hadn't encountered chain phenomena.Pea (Pisum sativum) has only 7 pairs of chromosomes, and Mendel studied exactly 7 pairs of traits.Was it luck that they weren't chained, saving Mendel an extra hassle?It does not appear to be the case.We know that Mendel spent several years conducting preliminary hybridization experiments before embarking on his pea experiments, and that he probably discarded some traits (or at least one of the paired traits) that did not show free assortment for several generations regardless of.It may also be that the seed dealer from whom he obtained his test material favors those traits which are freely assorted.Finally, the genetic map distance (distance) of some genes is large enough to show free assortment even if they are all on the same chromosome.
The exception to complete linkage became a serious problem when Morgan's group began to focus its efforts on analyzing the genetic architecture of Drosophila.Morgan and colleagues found that the magnitude of the broken linkage was large.Sometimes it can be as low as 1%, how can such variability be explained?
Take a special case as an example.There is a set of three recessive genes - yellow (body) color (y), white eye (w), winglet (m) - located on the X chromosome of Drosophila.If a male fly with these three genes is crossed with a normal female fly, it can be expected that these three recessive genes will appear in the F2 generation in the form of a linkage group.In fact, 1.3% of the yellow and white eye linkages were broken, 32.6% of the white eyelet linkages were broken, and 33.8% of the yellow winglet linkages were broken.How to interpret these figures?
The numerical values of these exceptions are usually mostly explained by the random process of unit exchange proposed by de Vry.But a different answer could be made based on cytological studies in the early 1900s.The study of the details of meiosis has come a long way in the 20 years since Beverly and Hertwick's pioneering work.Chromosomal (chromatic material) changes in the first prophase can be divided into at least 6 stages.There is a stage in which the two paired chromosomes are still thin, but each chromosome has separated into chromatin filaments (chromatids), the so-called tetratene stage.These two chromatids repeatedly cross each other to form a wavy ring.
The Belgian cytologist Janssens (1909) pointed out that when four chromatids are coiled around each other, a paternal and a maternal chromatid can be broken at the point where they cross each other, and the severed ends are always The severed head of the paternal monomer is attached to the severed head of the female singleton, and vice versa.The other two chromatids remain intact.
This creates a "chiasma," the point at which paired chromosomes remain in contact during the late phase of the first prophase of meiosis.According to Janssens, crossover represents the exchange of a paternal and a maternal chromosome.The end result will be a new chromosome made up of segments from both the paternal and maternal chromosomes.The incomplete linkage studied by Morgan's group is consistent with Janssens' idea.
The exchange process was so complex that it took almost 30 years to finally decide which explanation was correct (see Whitehouse, 1965. It is a book worth reading).However, it is now well documented that crossover occurs in tetratene and involves two of the four chromatids.It was also confirmed that the exchange occurred at the beginning of the fourth-line period (Gred, 1978).
摩根和他的助手斯特体范特LewiS，1961）认为源于交换的不完全连锁的份额表示遗传因子在染色体上所处位置之间的．直线距离。染色体在两个基因之间断裂的机会（也是交换的机会）取决于这两个基因在染色体上的距离；距离愈近，断裂机会愈少。
根据这一推理斯特体范特（当时年仅19岁！）推算了基因在染色体上的位置和顺序并制出了普通果蝇（Drosophilamelanogaster）的X染色体的第一份染色体图（发表于1913年）。他由之证实了当时所知道的这一染色体上的基因是沿着染色体作线性排列的。
在早期的实验中有一些结果相互矛盾。穆勒（Muller，1916）指出在一个长染色体上可能发生双交换而且交叉的存在将干扰在染色体上与交叉邻近处的进一步交换。考虑到这两种新发现的现象（双交换与干扰）就排除了上述矛盾，摩根的一些反对者正是利用这些矛盾来怀疑交换学说的正确性。
遗传现象的染色体学说现在已经可以用基因学说（Morgan，1926）来补充。1915年前后摩根及其同事研究了一百多种突变型基因。它们分成四个连锁群，和果蝇的四个染色体非常一致。连锁群的染色体实质的间接证明至此便告完整。然而一直到1931年Stern才运用某些异常基因（X基因片段贴附在第四个小染色体上）为交换提供了细胞学证明。同一年Creighton和麦克林托克（1931）在植物（玉米）方面也提出了类似证据。
后来玉米成了细胞遗传学的优良研究材料。虽然它没有后来在果蝇研究中非常有利的巨型染色体，但是它所含有的全部十个染色体在形态上都不同，而且有时还有额外的染色体存在。麦克林托克利用玉米的这些特点进行了30多年艰苦而又出色的研究来解释基因的作用；这一解释虽然内容丰富而又具有独到见解却一直等了很多年在分子遗传学家得到了相同结论之后才被举世公认。
这里所介绍的有关交换现象的历史是过于简化的，漏掉了很多复杂问题。例如交叉（由交换产生的染色体断片之间的桥梁）的实质一直长期争论不休。每一染色体臂上的交叉数目极不一致，事实上在某些情况下并没有交换现象，例如雄果蝇。关于第一次减数分裂中染色体的确切复制时间以及形成交叉（染色单体断裂及癒合）的确切时间，甚至交叉的存在是否总是表示交换现象都有很多争议。最重要的是，染色体中不同的染色单体的行为更是众说纷坛莫衷一是。因而作为解释交换现象的Janssens和摩根的断裂并合学说（breakase－fusion theory）并不被某些学者接受，例如Belling又另行提出了“副本选择”学说（copy-choice theory），Winkler提出“基因转变”学说（gene－con－version theory）。虽然这两种学说最后都没有得到公认，却促使人们进行了大量试验从而对交换现象以及基因的本质有了更深入的了解。现在还没有这三种学说的比较研究历史着作。对这些技术上的详细情况必须参阅细胞学和遗传学教科书。（另见Grell，1974）。重要的是，一切看来是例外的情况最终都能按经典染色体学说加以解释。
对进化过程来说由交换而实现的染色体重建非常重要。它是父本和母本基因相混合的有效机制，并通过产生基因在染色体内的新组合来提供非常丰富的新遗传型（其数量远远超过由突变所提供的）以便自然选择发挥作用。
染色体另外一个作用是能促进重组（recombination），即在成熟分裂的减数分裂中父本和母本染色体的独立运动。1902年以前普遍认为父本和母本的染色体组作为各自的单独单位运动。例如某些学者以为在卵细胞的成熟分裂时所有的父本染色体都以极体的形式被排除，然后通过受精由来自父本的新染色体组代替。如果真是这样，单性生殖卵在成熟时就不会产生极体，然而波弗利证明单性生殖卵不仅产生极体而且极体形成的方式和有性生殖卵的没有任何不同。另外，杂合的雌体产生具有父本基因的配子。最后，CarotherS（1913）发现在具有大小不同的（异形性）染色体组的物种中，较大的染色体随意向两极运动。这是父本的和母本的染色体组并不作为单一的单位进行分离的决定性证据。然而有一种罕见的遗传现象、“减数分裂驱动”（mciotic drive），阻止染色体任意移向两极。这能说明在某些情况下种群中保存了在其他情况下有害基因的现象。
染色体在形成交叉时偶尔会完全断裂，然后再按新的方式重新组装而不仅仅是在断裂处并合在一起。如果发生了两次断裂，中间的一段可以倒转过来，这就是染色体“倒位”。如果着丝粒不在倒位的染色体节上就是臂内倒位；如果着丝粒包括在这个染色体节内就称为臂间倒位。当染色体的某一片段断裂下来后附着在（或插入）另一个不是同源的染色体上就出现“易位”（现象）。有时也发生“不（相）等交换”，形成两个子染色体，其中一个染色体有重复，而另一个有缺失。两个（具有近端着丝粒的）染色体可能并合或一个（具有中间着丝料的）染色体可能进行分裂，这样的变化称为罗伯逊重排”（Robertsonian rearrangements）。最后，“多倍性”指的是多于染色体组基本数目两倍以上的染色体。所有这些染色体变化在进化上都具有潜在的重要意义，但丝毫也没有降低染色体遗传学说的价值。具有遗传影响的染色体重排往往称为“染色体突变”。我在这里没有逐一介绍这些染色体突变的发现历史，因为这对了解染色体进化并无意义。
17．9摩根与染色体学说
某些历史学家声称摩根及其研究小组是染色体遗传学说的创始人这种说法显然并不正确。染色体个体性的证实（这主要是波弗利的贡献）、茹的关于染色体必定是由不同性质的遗传颗粒直线排列而成的论点、以及孟德尔分离现象的发现，可以说必然会在1902－1904年导致瑟顿-波弗利的染色体遗传学说。这一学说提出后几乎立即就被大多数细胞学家接受，因为这只不过是以前20年细胞学发展的必然产物。
鉴于这学说的说服力极强却又遭到强烈反对（甚至包括最着名的遗传学家如贝特森·约翰逊，起初还有摩根），这不能不使历史学家感到相当迷惘。这显然涉及到生物学中两个主要学派之间根深蒂固的概念分歧。由于染色体学说是间接地根据许多不同的事实推论而得，而反对者所要求的则是证据，特别是实验证据。后来摩根小组及其他学者虽然提供了这些证据，但已是1910年以后的事，发生在摩根从染色体学说的反对者转变成支持者的时候。
摩根从1903年到1910年在一些着作和论文中曾尖刻地攻击染色体学说（Allen，1966）。他的反对论点很多，首先一点是这学说只是“推论”，缺乏实验根据。摩根认为凡是没有被实验证实的就算不上科学。他非常轻视“哲理化”。尤其重要的是，提出性状是由颗粒控制而且这些颗粒又位于各个不同的染色体上是和他的生物现象学说（见下）完全冲突的。
然而到了1910年摩根几乎在隔夜之间转变成染色体学说的主要支持者之一并提供了一些具有决定性的有利证据。怎样解释摩根的这一急剧转变？这一急剧变化从他在转变前后所发表文章的日期得到证明。
1910年8月“美国博物学家”杂志发表了一篇摩根（1910a）激烈攻击染色体学说的长达48页的论文（论文收到日期是2月），这正是在摩根的着名“白眼”论文（1910b）发表（7月27日，收到日期7月23B）之后的三个星期，这后一篇文章有助于摩根放弃他对染色体学说的反对态度。
1910年摩根是48岁，素以坚持己见着称；和贝特森相反，当新的实验表明他原先的解释不合适时他能够改变自己的想法（在一定程度上！）。然而摩根的思想显然还受到他周围智力（理智）环境的影响。他的一些发现证实了几乎10年前他的朋友和同事威尔逊（E．B．Wilson）向他陈述的意见。威尔逊的论点又被摩根出色的青年合作者队伍所深化。这些年轻人的特色是天资和性格的多样化，没有摩根的19世纪偏执。摩根小组成员的主要特点曾由Jack Schultz（1967）——他也是摩根小组的后期成员之一——作过如实的刻画：“摩根的怀疑态度和穆勒的系统观点……斯特体范特的卓越分析能力和布里奇斯的出色实验技巧。”这个小组的所有年轻成员，其中大多数人成天关在那小“果蝇室”内，都在摩根的领导下工作。在这个小组的四个成员中究竟是谁在哪些特殊方面强化或充实了染色体学说已无从查考，而且也无关紧要。研究摩根的史料专家是斯特体范特（1965a）和Allen（1967；1978），研究穆勒的是Carlson（1966；1974）和Roll-Hansen（1978b）。由于这些“果蝇室的居民”的多样性，他们非常融洽妥贴地相互补充并且作为一支队伍十分自如地运用假说一演经法。1911年以后很可能是穆勒，布里奇斯和斯特体范特提出大部分假说，而摩根则一如既往地坚决要求这些假说必须通过实验彻底地加以检验。
虽然摩根本人曾经发现（并正确地进行解释）交换现象以及基因学说的其他必需证据，然而也有很多间接证据表明他多少是一个勉强的“转变者”，有时还愿意溜回到他原先在1910年以前的思想中去。一直迟至1926年他放弃了物理主义者的偏见却又声称研究遗传现象的学者关于基因的一切结论皆来自“数字的和定量的数据……基因学说……完全由数字数据求出基因的性质（就这学说所赋予基因的性质而言）”，就好像，在染色体上的位置就是基因的唯一性质！
关于染色体学说的发展和迅速累积的遗传学数据的一致性早在1915年就由摩根、斯特体范特，穆勒和布里奇斯在他们合着的《孟德尔遗传学的机制》一书中非常明确地阐述过。因此为什么贝特森、约翰逊等还继续反对染色体学说就令人费解，为什么摩根的两个最亲密助手、斯特体范特和布里奇斯不仅没有忽视这学说反而感到需要用更新的实验来论证染色体学说的正确性。他们醉心于探索各种表面上的例外或矛盾情况，以便证明这些情况他们都可以用染色体学说加以解释。有人曾感到奇怪，他们为什么不像穆勒那样阖上书本去研究新问题。就我看来，从1915年到1930年在果蝇遗传学上具有高度创见和一丝不苟的研究工作基本上并没有对瑟顿-波弗理学说提出任何重要修正。反而这些研究却论证了这学说的正确性并指陈了它在生物学上的重要意义。
至于染色体学说为什么道到如此激烈的反对这个问题从研究当时的文献资料就可以找到答案（Coleman，1970；Roll-Han sen，1978b）。染色体学说不仅仅是生物学知识大厦的只石片瓦，更重要的倒是它是检验生物学中两种根本不同的哲学或两种对立的世界观的一个例证。在受精作用的实质上（接触或融合）以及19世纪的一些其他争论（例如细胞核的起源）上也都表明了这两种学派的分歧（另见Coleman，1965；Churchill，1971）。按1910年当时的情况很难说清这两个对立阵营。我有这样一种印象，即一方是物理主义者一后生论者一胚胎学家阵营，另一方是颗粒论者—先成论者—细胞学家阵营。
我这样划分时所用的称呼与1910年时的情况可能并不贴切。例如在1800年以后对任何一个人贴上先成论者的标签就十分容易引起误解。物理主义者原则上是极端的还原论者，但在这里他们分析入微的程度还不及颗粒论者。物理主义者也是机械论者，颗粒论者亦复如此。物理主义者总是搜索运动和力；他们偏好“动态”解释；他们企图将一切（定）量化并用数值表示。颗粒论者则按性质上不同的颗粒来解释生物学现象，按结构、形态、独特性、历史变化以及种群方面来解释。他们的“物质性”解释促使他们求助于分子（因而是化学）而不是力（从而不是物理学）。
人们在怎样称呼这两个阵营最确切这一点上可能有争议，但对它们在解释生物现象本质这个问题上根本不同这一点上则都是一致无疑的。贝特森、约翰逊以及摩根起初都是物理主义者，如果染色体遗传学说是正确的，这就意味着要否定他们自己的概念结构。
我将试图说明这在总体上或特殊问题上都是如此。
物理主义者对必须承认或接受颗粒（性）基因观点感到惊诧不安。对他们来说这无异于先成论以现代打扮复活。先成论与后生论之间的争论如果是以雏型人（homunculus）与活力（visviva）的形式相争当然早已结束。虽然在胚胎学诞生（1816－1828年左右）之后先成论的雏型人观点由于过于荒谬已不再被人考虑，但是自从生物学家意识到遗传现象的精确性后，后生论的一般化活力或发育力也同样站不住脚。对茹，魏斯曼和波弗利来说，遗传的精确性显然要求提出种质的结构，即遗传物质在结构上的复杂性，后来表现为瑟顿-波弗利染色体学说。物理主义者难于理解如果不是返回到Bonnet的朴素先成论怎么可能相信这样的观点。
对立面的一个比较充分的反对理由来自胚胎学。1883年茹提出的遗传物质等量分裂学说从表面上看来很快就被茹本人的镶嵌发育论点以及细胞谱系研究的结果所否定。
1890年代一个又一个的胚胎学发现似乎更容易被魏斯曼的种质不等分裂学说解释清楚，而孟德尔的均等分裂却难于解释。发育现象与瑟顿—波弗里学说之间的表面矛盾经过几十年的分析研究和概念更新才最后解决。
另外的一个反对理由来源于第一个颗粒遗传学说过于简单。在1900年代早期对遗传型和表现型之间的区别还并不清楚。虽然先成论的雏型人学说已被彻底否定，但在某些胚胎学家和遗传学家的思想中它却被另一种模式代替，即生物的每一个性状是由种质中的某一个特定遗传因子代表的。遗传型可以说成是微型的表现型，虽然不是雏型人却是遗传颗粒（不论是微芽、泛子或其它）的镶嵌，每个镶嵌相对于表现型的特定部分。这种想法表现在早期孟德尔主义者的“单位性状”概念中。德弗里（1889）特别指出泛子从细胞核移入细胞质，并在细胞质中发挥发育作用。因此体质是由发育后的泛子组成。
就物理主义者来说，这就是遗传现象的形态学说明，在原则上和古老的雏型人概念并没有什么不同。贝特森和约翰逊按照他们自己的观点特地批判了染色体学说的形态学解释。
曾经使魏斯曼、赫特维克以及德国胚胎学家困惑不解的传递与发育之间的关系也起了作用。摩根及其小组决定将这两个问题分开进行研究并从传递遗传学着手。贝特森和其他反对细胞学说的学者则继承了魏斯曼传统，需要有一种同时能够解释传递和发育的遗传学说。在身体各种各样的组织和器官中含有完全相同的染色体（具有直线排列的颗粒性基因）就他们看来和所观察到的发育现象并不相符。
只要无法区分遗传型和表现型，颗粒论者就不得不按遗传因子和体质性状之间一对一的关系的某种先成论考虑问题。某些承认单位性状学说的学者认为某个生物有多少性状就有多少遗传因子。因而以一贯性和逻辑性着称的魏斯曼主张在一切发育阶段中不同的性状必然有不同的定子，例如不仅是成蝶翅膀上的可以独立变化的每一性状而且同样还有毛虫的每个性状都有其定子。由于或多或少地认为遗传物质通过繁殖与生长直接转变成表现型是理所当然的事，所以这不单是一种逻辑结论而且可以说是一种必然的结论。
因此当凯塞尔发现表现型发生变化时（现在知道这是由于修饰基因的作用），他就只能按与一个基因一个性状假说相一致的观点来解释，并促使他提出了“污染学说”（见前）。
基因多效性（Pleiotropy）和多基因（Polygeny）的发现（见下文）最终导致了“单位性状”学说被否定（或至少是被大大修正）。这就使得染色体学说的追随者摆腕了粗俗的先成论影响从而有利于缩小两个阵营之间的鸿沟。然而这场论战毫无疑问是以颗粒论者轻而易举地取得胜利而结束。颗粒论者的学说最后被称为遗传的分子学说。
Carlson（1971）坚持认为穆勒在概念上是一位分子遗传学家，这当然是正确的，但穆勒并不是第一人。在穆勒以前的魏斯曼，德弗里和其他人早在1880年代就毫不含糊地提到遗传现象的分子基础。
必须强调的是这只是对两个阵营的争论和立场的极其简略的介绍。每个参与者，例如贝特森、约翰逊、赫特维克和摩根都各有自己的特殊混合观点，实际上有时是相当不合逻辑的、彼此矛盾的混合观点。然而染色体学说或者与他们的生物概念相一致，或者不一致。如果不一致，他们就必须或者反对或者放弃长期珍视的信念。贝特森和约翰逊无疑是最顽固的科学家。
在波弗利和E． B．威尔逊以后，染色体研究仍然非常富有成果。细胞遗传学、即染色体研究的发现和遗传学研究的发现两者的集成综合，由于下列工作而迅速发展：麦克林托克（1929）对玉米粗线期染色体的分析研究，Heitz与Bauer（1933）重新发现双翅目昆虫的巨大多线染色体，C． D． Darlinston对遗传系统的研究，M． J． D． White的研究，以及日益扩大的细胞学者队伍的研究。 1970年代染色体研究又进入了一个新的活跃时期。
这一领域的重要进展是采用了各种新技术的结果。例如目前通过组织培养（使细胞扩增），浸于低渗溶液（同样使细胞增大），秋水仙素处理（抑制纺锤体形成和使染色体收缩）等技术决定染色体数目远比过去的压片法精确可靠。又例如通过新技术使人类染色体数目从48个修正为46个。在很多研究中，诸如与人类遗传病有关基因的定位，正确鉴别个别染色体都非常重要。染色体在组成上很复杂，某些化学处理对其中不同组分的影响有区别因而在染色体上出现不同的带。根据所采用的显带技术不同可以分辨Q带、G带、R带、T带和C带（参阅Caspersson andZech 1972）。用放射性物质（氚）将活组织的染色体加以标记可以得到另一类重要信息。
这些研究中最重要的发现可能是了解到原核生物（细菌、蓝绿藻）和高等生物具有相同的遗传物质（核酸），但是由核酸组成的染色体的类型和高等生物的不一样。然而正是因为这些原核生物的DNA（或RNA）的组织结构非常简单，所以特别适合于进行某些类型的遗传学分析，尤其是基因功能和基因调节控制。因此一直到1970年早期分子遗传学的大部分研究都是采用原核生物作实验材料。
虽然目前对许多原核生物的DNA组织结构有了较多的了解，但是真核生物的染色体还很不容易分析（Cold Sprins HarborSymposia 1978）。目前还只知道DNA附着在（埋入？）蛋白质（特别是组蛋白）基质上，而且有迹象表明这些蛋白质在基因活性上具有决定性作用。然而尽管近年来已经发现了大量有关事实，就我看来，真核生物染色体作为一个整体，我们要提出一个解释它的结构和功能的完整学说还为时过早，还有很多工作要做。因此，承认遗传现象的染色体学说决不是染色体研究的结束，倒毋宁说是刚刚跨入染色体研究的一个新时代。
Fig. 2a The F1 generation male flies of the red-eyed female parent have the female X chromosome as red-eyed.50% of F1 females have F2 males with white eyes due to normal Mendelian segregation
Figure 2b In reciprocal crosses (reciprocal crosses), F1 female flies receive the maternal X chromosome.If the female parent is homozygous recessive white-eyed, all male offspring will be white-eyed, although the male parent is obviously red-eyed, and sex genes and eye color genes are not freely combined.
Based on the above observations, Morgan concluded in 1910 that the eye color factor (mutation from red to white) is coupled to the sex-determining X factor.A year later (1911: 384) he specifically explained this kind of trait coupling phenomenon from the perspective of chromosomes: "What we found was not random segregation in the Mendelian sense, but "factor associations" that are close together on chromosomes. of factors). Cytology provides the mechanism needed for experimental evidence." Other mutations, such as luteal body color and small wings, are also: sex-linked, that is, located on the sex chromosomes.Other trait linkage groups are not related to sex and are apparently on other chromosomes in Drosophila, which are called autosomes or common chromosomes (as distinguished from the sex chromosomes).
De Vry, Collens, Boverly, and Sutton had actually predicted the chain phenomenon theoretically.They reasoned from the individuality and continuity (through the mitotic cycle) of chromosomes.
Bridges (a member of Morgan's group) in 1914 provided a more convincing proof for the theory of chromosomal inheritance.F1 Generations produced equal numbers of heterozygous red-eyed females and white-eyed males.This is determined by the genetic makeup of the two parents, necessarily.
But in Morgan's lab an unusual line of fruit flies emerged that in such a cross experiment had about 4.3 percent of its F1 generation white-eyed females and red-eyed males.The details and explanations of this test are described in detail in classic genetics textbooks and will not be repeated here.Bridges had imagined that the female flies of this strain would have not only two X chromosomes but also a male Y chromosome.This XXY female fruit fly probably arose when an abnormal egg with two XX chromosomes (due to an error in meiosis) was fertilized by a Y sperm.When such an individual with three sex chromosomes (two X, one Y) forms gametes, or these two X chromosomes enter different gametes (eggs), X and XY eggs (actually formed gametes) are formed This is the case in 91.8% of the cases) more or two Xs enter one egg, and Y enters another egg, forming XX and Y eggs (about 8.2%). After normal, X or Y XXX and YY zygotes could not survive and died, but a small number of special red-eyed male flies (XY) and white-eyed female flies (XXy) were produced (see Figure 3). Bridges' idea was later confirmed by cytological observation , which confirms the existence of XXY female flies and XYY male flies in this strain of fruit flies.
Before (Wilson, 1909) and since then, some nondisjunction phenomena have been found, including individuals containing extra autosomes.For example, there are three chromosomes 21 in humans, known as trisomy 21 due to nondisjunction, which is the cause of Downs Syndrome (Downs Syndrome).In many plant species there are individuals who have an extra chromosome (trisomy) or have lost an autosome (monosomy).These individuals survived and were used to study various balancing effects of the same gene.For example, any trisomy of 12 pairs of chromosomes in the genus Datura not only survives but also has a special shape.The same is true for any single monomer of Nicotiana 23 chromosomes.
The significance of Bridges' study is that it provides the first direct evidence that a sex-linked gene is carried on the X chromosome.His conclusion was confirmed again and again later.Since then there has been less reason to object to the chromosome theory, although a few scholars, such as Bateson and Goldschmidt, remain skeptical, and even Morgan is somewhat equivocal.
17.8 Meiosis (Mature Division, Meiosis)
After 1902, although some biologists talked casually about the theory of chromosomal inheritance, its precise meaning was not very clear at that time.Most people refer to Roux's suggestion that the various genetic elements (now should be said genes) be arranged in a straight line on the chromosome.However, this is not the whole problem.Cytologists in the 1870s to 1890s discovered many chromosomal phenomena that were definitely related to heredity. After 1900, these phenomena were systematically studied, especially after 1910 by Morgan's research group, which greatly promoted the development of chromosome theory.
Let's start with the behavior of chromosomes during gamete formation.Both the nucleus of the egg and the sperm are "haploid," meaning they have half the number of chromosomes that a (diploid) somatic cell has.How is the number of chromosomes halved during gamete formation and how does this affect heredity?
Van Beneden (1883) discovered that when an roundworm egg is fertilized, the two chromosomes of the male sperm and the two chromosomes of the egg nucleus unite to form a new nucleus that is zygotic with four chromosomes.The resulting cleavage of this fertilized egg contains four chromosomes each; each cell is "diploid" and has twice as many chromosomes as the gamete.If the number of chromosomes were doubled at each fertilization, the offspring would have twice as many chromosomes as the parents, so each cell would soon have thousands of chromosomes.Clearly, some process must counteract the doubling of chromosome numbers during fertilization. Strasburger (1884) and Weissmann have successively proposed that "meiosis" must be carried out before the formation of gametes.Boverly (1887-1888) also agreed with Weisman's opinion, and later Hertwick made a detailed and correct description of the meiosis process in 1890.
Cytologists discovered that animals undergo two consecutive cell divisions during the formation of gametes, which are very different from normal mitosis, which was later called meiosis or mature division (me1os1s).Exactly what lenization (or rather how chromatin is reduced) occurs during meiosis has been long debated and unresolved.
The only fact that was quickly recognized at that time was that oocytes and spermatocytes (that is, the cells that eventually develop into eggs and sperm) had the same number of chromosomes as ordinary somatic cells, and they were all diploid; The resulting gametes (eggs and sperm) have half the number of chromosomes and are haploid.When the essence of meiosis is fully understood, it is known that the maturation of the nucleus of the egg cell is completely similar to that of the sperm; but at first glance, the maturation processes of these two types of cells are very different, so they will be introduced separately below.
The chromosome set of each nucleus is composed of a pair of homologous chromosomes, one from the father and the other from the mother.During the first meiotic division, the pair of homologous chromosomes are closely attached to each other from the side, and this pairing process is called "synapsis".At first the details of what happened in this pairing process were completely unclear; the two fit together so closely that microscopic analysis could not determine what was going on in the prophase of the first meiotic division.It took almost another 30 years for this process to be fundamentally understood through genetic analysis (see below).What Beverly and Hertwick observed was the separation of chromosomes after cataclysm (condensation phase), just as in normal mitosis.
In the egg cell this division is carried out at the periphery of the egg, a set of daughter chromosomes (daughter chromosomes) are excluded in the form of a single polar body.
The second nuclear division of meiosis is special because only the nucleus divides and the chromosomes do not divide.The result is that half of the chromosomes go to the daughter nucleus and the other half go to another nucleus.In roundworms, the number of chromosomes is thus reduced from four to two.This second division is called the reduction division by Weissmann.One of the two daughter nuclei in the egg cell is excluded as a second polar body.
The same two nuclear fissions also occur during the formation of male gametes, but the difference is that no daughter nuclei are expelled in the form of polar bodies.
Instead, a group of four spermatozoa was formed, which came from the .It is produced by a nucleus in spermatocytes during human meiosis, as pointed out by Hertwick (1890).Since the number of chromosomes does not double in the second meiosis, these four sperm also have half the number of chromosomes of the diploid somatic cells.What I present here is only the final explanation of what happens in meiosis, the details of which are assembled by the discoveries and explanations of VanBeneden, Hertwick, Weismann, and others; Churchill (1970) has The process of understanding the development of this issue has been brilliantly expounded.At first, Hertwick and Weissmann disagreed greatly with each other on interpretations, for two important reasons.Hertwick believed somewhat in fusogenic inheritance, in which the paternal and maternal chromosomes fuse with each other at fertilization, and he believed that after each cell division the chromosomes were dissolved and recomposed of dyed granules before the next round of cell division.In situ, the exclusion of polar bodies is simply a reduction in the amount of dyed material.Weismann, in contrast, argued that the paternal and maternal chromosomes remained separate after fertilization, and that each chromosome remained continuous throughout mitosis, meiosis, and the subsequent quiescent phase.On both issues Weissmann's assumptions turned out to be correct.The most important conclusion to be drawn from the foregoing controversy is that the polar bodies excreted by the egg contain exactly the same amount of chromosomes as those retained in the nucleus of the egg.Thus the division of the nucleus (meiosis) in the formation of female and male gametes is exactly the same, although in females the final result is the formation of one egg and three polar bodies, in males four spermatozoa.Although Hertwick and Weisman openly debated the technical details of cytology, as Churchill (1970) wisely pointed out, the essence was determined by their different positions and concepts.Hertwick represented the physicist camp of physiology, Weissmann represented the morphological particle theory molecular school.
We can also express the cytological content of meiosis in terms of genetics.It is assumed that the formation of a new zygote is the result of the fusion of the paternal and maternal chromosome sets, in which one chromosome with the allele A (from the paternal parent) matches a chromosome with the allele a (from the maternal parent) to produce the zygote Aa .From the first cleavage of this new zygote, the two homologous chromosomes will remain paired, and all somatic cells of the developing organism will be heterozygous for Aa.Only during the second mature division (meiosis) during gamete formation do the two homologous chromosomes separate, forming an equal number of gametes with gene A and gametes with gene a.Which chromosome gets into the daughter cell is purely accidental (see below).Mendel's law of segregation is thus satisfactorily explained by the observed behavior of chromosomes during fertilization and gamete formation.The introduction of meiosis can explain linkage and segregation phenomena very well here, but the problem is not over yet, and it cannot explain the incomplete linkage phenomenon pointed out above.But this can be illustrated by another process in meiosis, crossing over.Meiosis in plants is chromosomally identical to that in animals, but usually occurs at a different stage of the life cycle (before spore formation).
Since the traits of any organism and the genetic factors that determine these traits far exceed the number of chromosomes it contains, some people (Correns, 1902; Sutton, 1903,) thought that each chromosome must carry several (if not many) genes.This was quickly confirmed by Morgan's research team.However, the discovery of linkage groups (each linked to a particular chromosome) raised new questions.If all the genes on a chromosome were tightly linked together, then an organism would have only as many independent genetic units as there are chromosomes it contains.This imposes great constraints on reorganization.De Vry's (1903) study of F2 hybrids concluded that the possible chances of recombination in F2 hybrids were far from consistent with a full linkage view.He therefore proposed an "exchange of units" between paired parental chromosomes during the first prophase of meiosis.As to "how many and which (units will be exchanged) may be purely accidental" (1910: 243), this suggests that exchanges are always mutual exchanges.Boverly also predicted this type of exchange (1904:118).Genetic analysis quickly demonstrated that the linkage of genes on the same chromosome was incomplete.Bateson, Saunders, and Punnett (1905) were the first to conduct such observational studies.In F2 crosses of two varieties of sweet pea (Lathyrus) (different from each other in flower color and pollen grain shape), they neither obtained the expected 9:3:3:1 ratio nor the simple 3:1 ratio , but found 69.5% of double-dominant individuals, 19.3% of double-recessive individuals, and 5.6% of two types of heterozygotes.It is clear that the genes for these two traits are neither freely assortable nor fully linked (with an 11% exception).Bateson had proposed a special hypothesis to explain this phenomenon, but since he did not believe in chromosome theory, he did not consider exchange.
It used to be said that it was an oddity that Mendel hadn't encountered chain phenomena.Pea (Pisum sativum) has only 7 pairs of chromosomes, and Mendel studied exactly 7 pairs of traits.Was it luck that they weren't chained, saving Mendel an extra hassle?It does not appear to be the case.We know that Mendel spent several years conducting preliminary hybridization experiments before embarking on his pea experiments, and that he probably discarded some traits (or at least one of the paired traits) that did not show free assortment for several generations regardless of.It may also be that the seed dealer from whom he obtained his test material favors those traits which are freely assorted.Finally, the genetic map distance (distance) of some genes is large enough to show free assortment even if they are all on the same chromosome.
The exception to complete linkage became a serious problem when Morgan's group began to focus its efforts on analyzing the genetic architecture of Drosophila.Morgan and colleagues found that the magnitude of the broken linkage was large.Sometimes it can be as low as 1%, how can such variability be explained?
Take a special case as an example.There is a set of three recessive genes - yellow (body) color (y), white eye (w), winglet (m) - located on the X chromosome of Drosophila.If a male fly with these three genes is crossed with a normal female fly, it can be expected that these three recessive genes will appear in the F2 generation in the form of a linkage group.In fact, 1.3% of the yellow and white eye linkages were broken, 32.6% of the white eyelet linkages were broken, and 33.8% of the yellow winglet linkages were broken.How to interpret these figures?
The numerical values of these exceptions are usually mostly explained by the random process of unit exchange proposed by de Vry.But a different answer could be made based on cytological studies in the early 1900s.The study of the details of meiosis has come a long way in the 20 years since Beverly and Hertwick's pioneering work.Chromosomal (chromatic material) changes in the first prophase can be divided into at least 6 stages.There is a stage in which the two paired chromosomes are still thin, but each chromosome has separated into chromatin filaments (chromatids), the so-called tetratene stage.These two chromatids repeatedly cross each other to form a wavy ring.
The Belgian cytologist Janssens (1909) pointed out that when four chromatids are coiled around each other, a paternal and a maternal chromatid can be broken at the point where they cross each other, and the severed ends are always The severed head of the paternal monomer is attached to the severed head of the female singleton, and vice versa.The other two chromatids remain intact.
This creates a "chiasma," the point at which paired chromosomes remain in contact during the late phase of the first prophase of meiosis.According to Janssens, crossover represents the exchange of a paternal and a maternal chromosome.The end result will be a new chromosome made up of segments from both the paternal and maternal chromosomes.The incomplete linkage studied by Morgan's group is consistent with Janssens' idea.
The exchange process was so complex that it took almost 30 years to finally decide which explanation was correct (see Whitehouse, 1965. It is a book worth reading).However, it is now well documented that crossover occurs in tetratene and involves two of the four chromatids.It was also confirmed that the exchange occurred at the beginning of the fourth-line period (Gred, 1978).
摩根和他的助手斯特体范特LewiS，1961）认为源于交换的不完全连锁的份额表示遗传因子在染色体上所处位置之间的．直线距离。染色体在两个基因之间断裂的机会（也是交换的机会）取决于这两个基因在染色体上的距离；距离愈近，断裂机会愈少。
根据这一推理斯特体范特（当时年仅19岁！）推算了基因在染色体上的位置和顺序并制出了普通果蝇（Drosophilamelanogaster）的X染色体的第一份染色体图（发表于1913年）。他由之证实了当时所知道的这一染色体上的基因是沿着染色体作线性排列的。
在早期的实验中有一些结果相互矛盾。穆勒（Muller，1916）指出在一个长染色体上可能发生双交换而且交叉的存在将干扰在染色体上与交叉邻近处的进一步交换。考虑到这两种新发现的现象（双交换与干扰）就排除了上述矛盾，摩根的一些反对者正是利用这些矛盾来怀疑交换学说的正确性。
遗传现象的染色体学说现在已经可以用基因学说（Morgan，1926）来补充。1915年前后摩根及其同事研究了一百多种突变型基因。它们分成四个连锁群，和果蝇的四个染色体非常一致。连锁群的染色体实质的间接证明至此便告完整。然而一直到1931年Stern才运用某些异常基因（X基因片段贴附在第四个小染色体上）为交换提供了细胞学证明。同一年Creighton和麦克林托克（1931）在植物（玉米）方面也提出了类似证据。
后来玉米成了细胞遗传学的优良研究材料。虽然它没有后来在果蝇研究中非常有利的巨型染色体，但是它所含有的全部十个染色体在形态上都不同，而且有时还有额外的染色体存在。麦克林托克利用玉米的这些特点进行了30多年艰苦而又出色的研究来解释基因的作用；这一解释虽然内容丰富而又具有独到见解却一直等了很多年在分子遗传学家得到了相同结论之后才被举世公认。
这里所介绍的有关交换现象的历史是过于简化的，漏掉了很多复杂问题。例如交叉（由交换产生的染色体断片之间的桥梁）的实质一直长期争论不休。每一染色体臂上的交叉数目极不一致，事实上在某些情况下并没有交换现象，例如雄果蝇。关于第一次减数分裂中染色体的确切复制时间以及形成交叉（染色单体断裂及癒合）的确切时间，甚至交叉的存在是否总是表示交换现象都有很多争议。最重要的是，染色体中不同的染色单体的行为更是众说纷坛莫衷一是。因而作为解释交换现象的Janssens和摩根的断裂并合学说（breakase－fusion theory）并不被某些学者接受，例如Belling又另行提出了“副本选择”学说（copy-choice theory），Winkler提出“基因转变”学说（gene－con－version theory）。虽然这两种学说最后都没有得到公认，却促使人们进行了大量试验从而对交换现象以及基因的本质有了更深入的了解。现在还没有这三种学说的比较研究历史着作。对这些技术上的详细情况必须参阅细胞学和遗传学教科书。（另见Grell，1974）。重要的是，一切看来是例外的情况最终都能按经典染色体学说加以解释。
对进化过程来说由交换而实现的染色体重建非常重要。它是父本和母本基因相混合的有效机制，并通过产生基因在染色体内的新组合来提供非常丰富的新遗传型（其数量远远超过由突变所提供的）以便自然选择发挥作用。
染色体另外一个作用是能促进重组（recombination），即在成熟分裂的减数分裂中父本和母本染色体的独立运动。1902年以前普遍认为父本和母本的染色体组作为各自的单独单位运动。例如某些学者以为在卵细胞的成熟分裂时所有的父本染色体都以极体的形式被排除，然后通过受精由来自父本的新染色体组代替。如果真是这样，单性生殖卵在成熟时就不会产生极体，然而波弗利证明单性生殖卵不仅产生极体而且极体形成的方式和有性生殖卵的没有任何不同。另外，杂合的雌体产生具有父本基因的配子。最后，CarotherS（1913）发现在具有大小不同的（异形性）染色体组的物种中，较大的染色体随意向两极运动。这是父本的和母本的染色体组并不作为单一的单位进行分离的决定性证据。然而有一种罕见的遗传现象、“减数分裂驱动”（mciotic drive），阻止染色体任意移向两极。这能说明在某些情况下种群中保存了在其他情况下有害基因的现象。
染色体在形成交叉时偶尔会完全断裂，然后再按新的方式重新组装而不仅仅是在断裂处并合在一起。如果发生了两次断裂，中间的一段可以倒转过来，这就是染色体“倒位”。如果着丝粒不在倒位的染色体节上就是臂内倒位；如果着丝粒包括在这个染色体节内就称为臂间倒位。当染色体的某一片段断裂下来后附着在（或插入）另一个不是同源的染色体上就出现“易位”（现象）。有时也发生“不（相）等交换”，形成两个子染色体，其中一个染色体有重复，而另一个有缺失。两个（具有近端着丝粒的）染色体可能并合或一个（具有中间着丝料的）染色体可能进行分裂，这样的变化称为罗伯逊重排”（Robertsonian rearrangements）。最后，“多倍性”指的是多于染色体组基本数目两倍以上的染色体。所有这些染色体变化在进化上都具有潜在的重要意义，但丝毫也没有降低染色体遗传学说的价值。具有遗传影响的染色体重排往往称为“染色体突变”。我在这里没有逐一介绍这些染色体突变的发现历史，因为这对了解染色体进化并无意义。
17．9摩根与染色体学说
某些历史学家声称摩根及其研究小组是染色体遗传学说的创始人这种说法显然并不正确。染色体个体性的证实（这主要是波弗利的贡献）、茹的关于染色体必定是由不同性质的遗传颗粒直线排列而成的论点、以及孟德尔分离现象的发现，可以说必然会在1902－1904年导致瑟顿-波弗利的染色体遗传学说。这一学说提出后几乎立即就被大多数细胞学家接受，因为这只不过是以前20年细胞学发展的必然产物。
鉴于这学说的说服力极强却又遭到强烈反对（甚至包括最着名的遗传学家如贝特森·约翰逊，起初还有摩根），这不能不使历史学家感到相当迷惘。这显然涉及到生物学中两个主要学派之间根深蒂固的概念分歧。由于染色体学说是间接地根据许多不同的事实推论而得，而反对者所要求的则是证据，特别是实验证据。后来摩根小组及其他学者虽然提供了这些证据，但已是1910年以后的事，发生在摩根从染色体学说的反对者转变成支持者的时候。
摩根从1903年到1910年在一些着作和论文中曾尖刻地攻击染色体学说（Allen，1966）。他的反对论点很多，首先一点是这学说只是“推论”，缺乏实验根据。摩根认为凡是没有被实验证实的就算不上科学。他非常轻视“哲理化”。尤其重要的是，提出性状是由颗粒控制而且这些颗粒又位于各个不同的染色体上是和他的生物现象学说（见下）完全冲突的。
然而到了1910年摩根几乎在隔夜之间转变成染色体学说的主要支持者之一并提供了一些具有决定性的有利证据。怎样解释摩根的这一急剧转变？这一急剧变化从他在转变前后所发表文章的日期得到证明。
1910年8月“美国博物学家”杂志发表了一篇摩根（1910a）激烈攻击染色体学说的长达48页的论文（论文收到日期是2月），这正是在摩根的着名“白眼”论文（1910b）发表（7月27日，收到日期7月23B）之后的三个星期，这后一篇文章有助于摩根放弃他对染色体学说的反对态度。
1910年摩根是48岁，素以坚持己见着称；和贝特森相反，当新的实验表明他原先的解释不合适时他能够改变自己的想法（在一定程度上！）。然而摩根的思想显然还受到他周围智力（理智）环境的影响。他的一些发现证实了几乎10年前他的朋友和同事威尔逊（E．B．Wilson）向他陈述的意见。威尔逊的论点又被摩根出色的青年合作者队伍所深化。这些年轻人的特色是天资和性格的多样化，没有摩根的19世纪偏执。摩根小组成员的主要特点曾由Jack Schultz（1967）——他也是摩根小组的后期成员之一——作过如实的刻画：“摩根的怀疑态度和穆勒的系统观点……斯特体范特的卓越分析能力和布里奇斯的出色实验技巧。”这个小组的所有年轻成员，其中大多数人成天关在那小“果蝇室”内，都在摩根的领导下工作。在这个小组的四个成员中究竟是谁在哪些特殊方面强化或充实了染色体学说已无从查考，而且也无关紧要。研究摩根的史料专家是斯特体范特（1965a）和Allen（1967；1978），研究穆勒的是Carlson（1966；1974）和Roll-Hansen（1978b）。由于这些“果蝇室的居民”的多样性，他们非常融洽妥贴地相互补充并且作为一支队伍十分自如地运用假说一演经法。1911年以后很可能是穆勒，布里奇斯和斯特体范特提出大部分假说，而摩根则一如既往地坚决要求这些假说必须通过实验彻底地加以检验。
虽然摩根本人曾经发现（并正确地进行解释）交换现象以及基因学说的其他必需证据，然而也有很多间接证据表明他多少是一个勉强的“转变者”，有时还愿意溜回到他原先在1910年以前的思想中去。一直迟至1926年他放弃了物理主义者的偏见却又声称研究遗传现象的学者关于基因的一切结论皆来自“数字的和定量的数据……基因学说……完全由数字数据求出基因的性质（就这学说所赋予基因的性质而言）”，就好像，在染色体上的位置就是基因的唯一性质！
关于染色体学说的发展和迅速累积的遗传学数据的一致性早在1915年就由摩根、斯特体范特，穆勒和布里奇斯在他们合着的《孟德尔遗传学的机制》一书中非常明确地阐述过。因此为什么贝特森、约翰逊等还继续反对染色体学说就令人费解，为什么摩根的两个最亲密助手、斯特体范特和布里奇斯不仅没有忽视这学说反而感到需要用更新的实验来论证染色体学说的正确性。他们醉心于探索各种表面上的例外或矛盾情况，以便证明这些情况他们都可以用染色体学说加以解释。有人曾感到奇怪，他们为什么不像穆勒那样阖上书本去研究新问题。就我看来，从1915年到1930年在果蝇遗传学上具有高度创见和一丝不苟的研究工作基本上并没有对瑟顿-波弗理学说提出任何重要修正。反而这些研究却论证了这学说的正确性并指陈了它在生物学上的重要意义。
至于染色体学说为什么道到如此激烈的反对这个问题从研究当时的文献资料就可以找到答案（Coleman，1970；Roll-Han sen，1978b）。染色体学说不仅仅是生物学知识大厦的只石片瓦，更重要的倒是它是检验生物学中两种根本不同的哲学或两种对立的世界观的一个例证。在受精作用的实质上（接触或融合）以及19世纪的一些其他争论（例如细胞核的起源）上也都表明了这两种学派的分歧（另见Coleman，1965；Churchill，1971）。按1910年当时的情况很难说清这两个对立阵营。我有这样一种印象，即一方是物理主义者一后生论者一胚胎学家阵营，另一方是颗粒论者—先成论者—细胞学家阵营。
我这样划分时所用的称呼与1910年时的情况可能并不贴切。例如在1800年以后对任何一个人贴上先成论者的标签就十分容易引起误解。物理主义者原则上是极端的还原论者，但在这里他们分析入微的程度还不及颗粒论者。物理主义者也是机械论者，颗粒论者亦复如此。物理主义者总是搜索运动和力；他们偏好“动态”解释；他们企图将一切（定）量化并用数值表示。颗粒论者则按性质上不同的颗粒来解释生物学现象，按结构、形态、独特性、历史变化以及种群方面来解释。他们的“物质性”解释促使他们求助于分子（因而是化学）而不是力（从而不是物理学）。
人们在怎样称呼这两个阵营最确切这一点上可能有争议，但对它们在解释生物现象本质这个问题上根本不同这一点上则都是一致无疑的。贝特森、约翰逊以及摩根起初都是物理主义者，如果染色体遗传学说是正确的，这就意味着要否定他们自己的概念结构。
我将试图说明这在总体上或特殊问题上都是如此。
物理主义者对必须承认或接受颗粒（性）基因观点感到惊诧不安。对他们来说这无异于先成论以现代打扮复活。先成论与后生论之间的争论如果是以雏型人（homunculus）与活力（visviva）的形式相争当然早已结束。虽然在胚胎学诞生（1816－1828年左右）之后先成论的雏型人观点由于过于荒谬已不再被人考虑，但是自从生物学家意识到遗传现象的精确性后，后生论的一般化活力或发育力也同样站不住脚。对茹，魏斯曼和波弗利来说，遗传的精确性显然要求提出种质的结构，即遗传物质在结构上的复杂性，后来表现为瑟顿-波弗利染色体学说。物理主义者难于理解如果不是返回到Bonnet的朴素先成论怎么可能相信这样的观点。
对立面的一个比较充分的反对理由来自胚胎学。1883年茹提出的遗传物质等量分裂学说从表面上看来很快就被茹本人的镶嵌发育论点以及细胞谱系研究的结果所否定。
1890年代一个又一个的胚胎学发现似乎更容易被魏斯曼的种质不等分裂学说解释清楚，而孟德尔的均等分裂却难于解释。发育现象与瑟顿—波弗里学说之间的表面矛盾经过几十年的分析研究和概念更新才最后解决。
另外的一个反对理由来源于第一个颗粒遗传学说过于简单。在1900年代早期对遗传型和表现型之间的区别还并不清楚。虽然先成论的雏型人学说已被彻底否定，但在某些胚胎学家和遗传学家的思想中它却被另一种模式代替，即生物的每一个性状是由种质中的某一个特定遗传因子代表的。遗传型可以说成是微型的表现型，虽然不是雏型人却是遗传颗粒（不论是微芽、泛子或其它）的镶嵌，每个镶嵌相对于表现型的特定部分。这种想法表现在早期孟德尔主义者的“单位性状”概念中。德弗里（1889）特别指出泛子从细胞核移入细胞质，并在细胞质中发挥发育作用。因此体质是由发育后的泛子组成。
就物理主义者来说，这就是遗传现象的形态学说明，在原则上和古老的雏型人概念并没有什么不同。贝特森和约翰逊按照他们自己的观点特地批判了染色体学说的形态学解释。
曾经使魏斯曼、赫特维克以及德国胚胎学家困惑不解的传递与发育之间的关系也起了作用。摩根及其小组决定将这两个问题分开进行研究并从传递遗传学着手。贝特森和其他反对细胞学说的学者则继承了魏斯曼传统，需要有一种同时能够解释传递和发育的遗传学说。在身体各种各样的组织和器官中含有完全相同的染色体（具有直线排列的颗粒性基因）就他们看来和所观察到的发育现象并不相符。
只要无法区分遗传型和表现型，颗粒论者就不得不按遗传因子和体质性状之间一对一的关系的某种先成论考虑问题。某些承认单位性状学说的学者认为某个生物有多少性状就有多少遗传因子。因而以一贯性和逻辑性着称的魏斯曼主张在一切发育阶段中不同的性状必然有不同的定子，例如不仅是成蝶翅膀上的可以独立变化的每一性状而且同样还有毛虫的每个性状都有其定子。由于或多或少地认为遗传物质通过繁殖与生长直接转变成表现型是理所当然的事，所以这不单是一种逻辑结论而且可以说是一种必然的结论。
因此当凯塞尔发现表现型发生变化时（现在知道这是由于修饰基因的作用），他就只能按与一个基因一个性状假说相一致的观点来解释，并促使他提出了“污染学说”（见前）。
基因多效性（Pleiotropy）和多基因（Polygeny）的发现（见下文）最终导致了“单位性状”学说被否定（或至少是被大大修正）。这就使得染色体学说的追随者摆腕了粗俗的先成论影响从而有利于缩小两个阵营之间的鸿沟。然而这场论战毫无疑问是以颗粒论者轻而易举地取得胜利而结束。颗粒论者的学说最后被称为遗传的分子学说。
Carlson（1971）坚持认为穆勒在概念上是一位分子遗传学家，这当然是正确的，但穆勒并不是第一人。在穆勒以前的魏斯曼，德弗里和其他人早在1880年代就毫不含糊地提到遗传现象的分子基础。
必须强调的是这只是对两个阵营的争论和立场的极其简略的介绍。每个参与者，例如贝特森、约翰逊、赫特维克和摩根都各有自己的特殊混合观点，实际上有时是相当不合逻辑的、彼此矛盾的混合观点。然而染色体学说或者与他们的生物概念相一致，或者不一致。如果不一致，他们就必须或者反对或者放弃长期珍视的信念。贝特森和约翰逊无疑是最顽固的科学家。
在波弗利和E． B．威尔逊以后，染色体研究仍然非常富有成果。细胞遗传学、即染色体研究的发现和遗传学研究的发现两者的集成综合，由于下列工作而迅速发展：麦克林托克（1929）对玉米粗线期染色体的分析研究，Heitz与Bauer（1933）重新发现双翅目昆虫的巨大多线染色体，C． D． Darlinston对遗传系统的研究，M． J． D． White的研究，以及日益扩大的细胞学者队伍的研究。 1970年代染色体研究又进入了一个新的活跃时期。
这一领域的重要进展是采用了各种新技术的结果。例如目前通过组织培养（使细胞扩增），浸于低渗溶液（同样使细胞增大），秋水仙素处理（抑制纺锤体形成和使染色体收缩）等技术决定染色体数目远比过去的压片法精确可靠。又例如通过新技术使人类染色体数目从48个修正为46个。在很多研究中，诸如与人类遗传病有关基因的定位，正确鉴别个别染色体都非常重要。染色体在组成上很复杂，某些化学处理对其中不同组分的影响有区别因而在染色体上出现不同的带。根据所采用的显带技术不同可以分辨Q带、G带、R带、T带和C带（参阅Caspersson andZech 1972）。用放射性物质（氚）将活组织的染色体加以标记可以得到另一类重要信息。
这些研究中最重要的发现可能是了解到原核生物（细菌、蓝绿藻）和高等生物具有相同的遗传物质（核酸），但是由核酸组成的染色体的类型和高等生物的不一样。然而正是因为这些原核生物的DNA（或RNA）的组织结构非常简单，所以特别适合于进行某些类型的遗传学分析，尤其是基因功能和基因调节控制。因此一直到1970年早期分子遗传学的大部分研究都是采用原核生物作实验材料。
虽然目前对许多原核生物的DNA组织结构有了较多的了解，但是真核生物的染色体还很不容易分析（Cold Sprins HarborSymposia 1978）。目前还只知道DNA附着在（埋入？）蛋白质（特别是组蛋白）基质上，而且有迹象表明这些蛋白质在基因活性上具有决定性作用。然而尽管近年来已经发现了大量有关事实，就我看来，真核生物染色体作为一个整体，我们要提出一个解释它的结构和功能的完整学说还为时过早，还有很多工作要做。因此，承认遗传现象的染色体学说决不是染色体研究的结束，倒毋宁说是刚刚跨入染色体研究的一个新时代。