As the proverbial saying goes "In the beginning" what were the initial thoughts of life scientists about a gene?   Believe it or not, early in biology, the concept of some sort of material being transmitted from one generation to give rise to the next generation was not even considered.  Rather, there was a belief in spontaneous generation.   Life arose spontaneously.  Ample examples were given in the very early textbooks of butterflies or houseflies arising in semi-sealed containers containing nothing more than some debris at the beginning of the experiment. Looking back of course, the obvious explanation is that the debris contained eggs or other life stages that hatched out or molted into the adult stage visible to the early investigators. (How these investigators viewed sexual matings and human birth is an interesting question although I am told that isolated tribes of people have been found in very recent times who did not understand this cause - effect relationship.)

        Only when the notion of spontaneous  generation of life was discarded and the need for fertilization and the concept of species were accepted did the early investigators seriously address the nature of material past from one generation to the next.   One interesting idea  -- falling  under the label of "pangenesis"  -- was that pieces of each body part were taken, assembled and then passed to the next generation.  Support of this came from interpretations of microscope views in which small men could be seen in samples of human sperm.  ( I am not sure where women came from !!!).  This idea was discredited when people discovered the process of   differentiation .   (There is a section in this course dealing with developmental genetics, so lots more then.)

        By late in the 19th century, biologists generally accepted the idea of genetic material.  Plants and animals of agricultural importance were usually used in these studies and traits like height, weight gain, yield, etc. (traits that are now termed quantitative traits)  were studied.  Because crosses of two lines led to progeny exhibiting a continuous range in the trait being studied, the Blending theory of genetics arose.  Like mixing white paint and black paint and getting gray paint, investigators believed that the heritable material controlling a particular trait  must be almost incomputable in number.
 
 

The work of Gregor Mendel marked the beginning of modern genetics

         It is the work of Gregor Mendel that dispelled the idea of the blending theory and replaced it with the particulate theory of genetics.  Because, as Mendel showed, the number of heritable units controlling a trait is few in a particular cross, investigators realized that the identification and study of each of these factors was a tractable scientific pursuit.  This is one of the major reasons why Mendel receives so much credit and why most biological scientists consider Mendel's work the beginning of the field of genetics. An English translation of Mendel's original paper can be found at http://www.esp.org/foundations/genetics/classical/gm-65.pdf .   (I suggest copying and pasting into the the address slot.)

         Mendel not only replaced the blending theory with the particulate theory, he also gave us two principles that form the basis of genetics.  These are the Law of Segregation and the Law of Independent Assortment.   We will define and place much emphasis on these in the next couple of lectures.  He also showed that alleles occur in pairs in the diploid pea and he gave us the concept of dominance.

         (Likely,  most of you know the history of Gregor Mendel.  He was an Austrian Monk who developed an interest in heredity, worked with peas and published his work in the 1870's.   His publication was discovered by three independent investigators at the turn of the century, and all three quickly realized the significance of the work.   Unfortunately, Mendel died before his work was rediscovered.)

         One of the keys to Mendel's success and a fact that distinguished his work from that preceding it was the use of mutants with phenotypes drastically different from the normal types.  Because of this and of extreme importance, Mendel realized that the types of phenotypes and their frequencies seen in subsequent generations could be explained by the inheritance of pairs of factors for a particular trait.   His interpretation   – now so obvious in hindsight  – was quite powerful and changed the way people thought about heredity.
 

 Some of Mendel's mutants included the following:

        The key observation, leading to the particulate theory,  was that Mendel could recover the two contrasting plant characteristics (what we now call phenotypes) from crosses involving plants of the two different phenotypes.  For example, he crossed the typically tall plants from a stock having only tall plants with short plants from a stock having only short or mutant plants.  All of the resulting progeny (what we now call the F1) were tall,  like one of the parents.  Mendel then allowed the F1 plants to self pollinate, and in the next (F2) generation,  plants were either like one of the original parents (75% of the total population was tall) or like the other parent (25% of the total population was short).  Were the blending theory operational,  plants having either of the two parental phenotypes would have been impossible to obtain. Note also that the  F1 generation had the phenotype of one of the two parents; an observation also not consistent with the blending theory.   Hence the blending theory was replaced by the particulate theory.
 

The Law of Segregation can also be gleaned from these data:

    Mendel noted that the F 2 plants were either tall or short. No new types were found. This led him to suggest the Law of Segregation. Factors controlling the particular trait separated cleanly one from the other and there is no mixing.

Mendel also described dominance:

    Mendel noted that the hybrid (F1) plants were indistinguishable in height from the tall parent in terms of height even though these plants contained genetic factors that could produce dwarf plants in subsequent generations. Mendel concluded that the genetic factor for tall is dominant to the factor for short.

    The proportion of plants in the F2 generation with the two parental phenotypes and the dominance relationship noted in the F1 generation led Mendel to suggest that each parent contributes one factor for the trait to the progeny:

    The ratio of 3:1 in the F2 generation led Mendel to suggest that factors (we now call these alleles) occur in pairs. Each parent contributes one of the two factors. The gametes arising from the F1 plants contain either one or the other member of the pair. Furthermore, to explain the 3 to 1 ratio in the F2 generation, gametes from the F 1 plants would carry each member with equal (50%) frequency. For example, if we assign the letter d for dwarf and D for tall, the F 1 plant would be Dd. Furthermore ½ of the sperm and ½ of the eggs would contain D, the other half would contain  d. Given random fusion or fertilization events, the pairs of alleles in the F 2 generation would be, DD, Dd, dD and dd. All occur in equal frequency. Since D is dominant to d (remember the F1 plants were tall), then DD, Dd and dD would all be tall (i.e. have the same phenotype). The only plants with a distinguishable phenotype are dd. They are short.

 Mendel's second law, Law of Independent Assortment:

        Mendel also noted that the trait for wrinkled seed behaved in an identical manner. It was recessive to round and F2 families segregated in a 3 round  to 1 wrinkled manner.

        Mendel also crossed short plants with round seed with tall plants with wrinkled seed. The F1 was tall with round seed. This is expected since tall is dominant to short and round is dominant to wrinkled. In the F2, he noted 9/16 tall and round, 3/16 short and round, 3/16 tall and wrinkled and 1/16 short and wrinkled.

    Mendel explained this in the following way. The factors for plant height (defined above as D and d) assort independently from those factors for seed texture (let's call them W for round and w for wrinkled). The factors for seed texture follow the same rules as those for plant height, they just simply separate independently of those for plant height. Stated in another way, the probability that a gamete will carry W or w is unaffected by the presence of D or d. The fact that this is so is called The Law of Independent Assortment.

        In more modern words, alleles of one gene segregate while alleles of different genes assort independently. (One fact that still entertains modern-day geneticists is why Mendel did not discover linkage. Hence, strictly speaking and quantitatively, the Law of Independent Assortment is violated when alleles of different genes are linked at a distance less than 50 map units. However the principle that Mendel described is valid and is extremely valuable to modern genetics.)

    To emphasize the two laws, one should note the following. In the first set of data ( tall versus short), all the plants in the F2 generation had one parental phenotype or the other parental phenotype. They were tall or they were short. No non-parental types or recombinants were found. From this, we conclude that the two differing genetic factors (i.e. alleles ) are different forms of one gene. Alleles segregate.

        In contrast, think about the data in the second experiment (tall wrinkled crossed with short round). Note that in the F2  generation we observed non-parental or recombinant types. We obtained four classes. Two of these are parental (tall wrinkled and short round) while the other two (tall round and short wrinkled) are non-parental or recombinant. From this, we conclude that there are two separate genes. One is for plant height while the other is for seed texture.

        To summarize, Mendel taught us five things: (1) genetic factors are particulate since parental phenotypes are recovered in subsequent generations , (2) there exists dominance.  One factor can dominate the other,   (3) factors -what we now call alleles - occur in pairs. Each parent contributes one member of each pair (this explains 3:1 F2  ratios,  (4) alleles of one gene segregate. -  The Law of Segretation and  (5) alleles of different genes assort independently - The Law of Independent Assortment.

 What Mendel's data do not mean:

A very important point that should be made in this regard is what can be properly concluded from a 3 to 1 F2 ratio. For example, the F2 ratio of 3 to 1 for plant height noted above means that in this particular cross, there exists genetic heterogeneity for one of the genes involved in determining plant height. THE DATA DO NOT MEAN THAT THERE IS ONLY ONE GENE FOR PLANT HEIGHT. In a classical genetic analysis, one identifies only those genes for which there exist physiologically-relevant differences in the two alleles of that gene.  While this sounds obvious -- and it is  -- it is a fact that is somehow lost by people in their studies or investigations.

    Another good thing to remember is that vast majority (but not all) recessive mutants giving rise to a detectable phenotype are loss-of-function mutants. Loss can be total (a null mutant) or it can be partial (a leaky mutant).

    To a large extent, showing that a gene for plant height is different from that for seed texture seems trivial by today's standards. Generally that is the case although genetic literature is filled with cases in which a single gene has many effects ( called pleiotropic effects). Hence, a gene affecting two such diverse traits is not totally farfetched.

    Lets take a more interesting case. Suppose that we find a recessive dwarf pea plant mutant in Austria and we find another recessive one in South Florida.

    Do you think that these mutants are mutant in the same gene or in different genes?

    Another way of thinking about this is how many gene functions does it take to make a plant tall. A good way to think about this is via a pathway. Compound A is converted to compound B to C, to D to E, etc. until we see this pathway manifested as a tall plant. There must be tens if not hundreds or thousands of gene functions required. Given this thinking, the chance of two mutants occurring in the same gene when there are so many targets should be quite small.
 
 

    So, how would we determine whether are two recessive dwarfs are mutant of the same gene or different genes?