Meiosis is responsible for Mendel’s principles

Scientists during Mendel’s time were so ingrained into the dogma of blended inheritance, that they simply discounted his work as an anomaly. Consequently, his work was disregarded and eventually forgotten. Three decades later, two scientists working independently ‘discovered’ the principles originally proposed by Mendel: Walter Sutton and Theodor Boveri.

While Mendel discovered the basic patterns of inheritance, he could not ascertain the underlying processes that generated those patterns. What wasn’t clear to Mendel, became apparent to Sutton and Boveri. In the decades following Mendel’s discoveries, the production of gamete cells (sperm and eggs) had been intensively investigated, uncovering how parental chromosomes split in the process of meiosis. Sutton and Boveri predicted that the patterns of meiosis could account for the patterns Mendel observed.

Meiosis explains Mendel's Principles of Segregation and Independent Assortment

Meiosis explains Mendel's Principles of Segregation and Independent Assortment

Meiosis explains Mendel’s principle of segregation

Mendel’s principle of segregation asserts that an organism has two (assuming diploploidy, 2n) alleles (Mendel called them ‘particles’) for each gene. A gene determines a physical characteristic (phenotype, i.e. flower color). Additionally, Mendel suggested that the offspring from a mating will only receive one ‘particle’ (allele) from each parent, and that the probability of getting a specific allele is 50%. In other words, during meiosis, each gamete cell has an equal probability of acquiring an allele of a specific gene. He concluded that the consistency of the phenotypic ratio in the F2 generation (3 dominant: 1 recessive), is only possible if each gamete has an equal probability of acquiring one allele over the second. But how?

A diploid (2n) organism, like humans, have two versions of each chromosome known as homologous chromosomes. In humans, one homologous chromosomes comes from the mother, the other one from the father. Each chromosome consists of several alleles. Homologous chromosomes have the same sequence of alleles, however the alleles can differ between the homologous chromosomes. Therefore, on one homologous chromosome you can have a dominant allele (i.e. F), while on the other you can have a recessive allele (i.e. f).

Meiosis explains Mendel's Law of Segregation

Meiosis explains Mendel's Law of Segregation

In interphase prior to mitosis, the homologous chromosomes are copied. In meiosis I, homologous chromosomes are paired up, and then split during anaphase I and eventually into two different cells during cytokinesis I. Each cell at the end of meiosis I has either a pair of one identical homologous chromosome or the other. 

In meiosis II, the paired identical homologous chromosomes split again, generating the gametes, which have one unpaired homologous chromosome for each chromosome. Gametes have half the number of chromosomes as normal body cells. 

Meiosis explains Mendel’s principle of independent assortment

Mendel found that the phenotypes he was studying were independently assorted. For example, he found that purple-flowered plants can have green seeds or yellow seeds, while white flowered plants can also have green or yellow seeds. In other words, flower color was not dependent on seed color. But how?

Again, the developing understanding of meiosis helped us determine how Mendel’s traits were independently assorted. Fig. 1 is a simplification of meiosis in eukaryotes, in that it only follows the segregation of a single homologous chromosome (2n=2). In reality, eukaryotes have several chromosomes. Humans have 46 different chromosomes that are paired (homologous), and said to be 2n=46. Boveri and Sutton reasoned that if the genes coding for Mendel’s phenotypes were on different chromosomes, the chromosomes assort independently during meiosis.

Meiosis explains Mendel's Principle of Independent Assortment

Meiosis explains Mendel's Principle of Independent Assortment

Sex-linked Genes

While Boveri and Sutton hypothesized that Mendel’s principles were related to meiosis, they didn’t have any experimental evidence to support their claim. That evidence came in from the lowly fruit fly, Drosophila melanogaster. At the turn of the 20th century, a biologist named Thomas Hunt Morgan began studying the fruit fly with the hopes of understanding inheritance in animals. This was a daunting task because unlike plants, animals can not be self-fertilized. He chose the fruit fly for three main reasons. First, they are really easy to keep alive...just give them fruit! Second, a fruit fly has an extremely short generation time (about 10 days). Data from many generations can be accrued in a relatively short amount of time. Third, fruit flies have a tremendous amount of phenotypic variation.

In his studies, he noticed a fly with a white eye. No one had ever seen a white-eyed fruit fly before (all others had red eyes). He inferred that this was a mutation in the DNA that was expressed in the eye color. He then designed a set of crosses in order to determine how eye color was inherited. 

While Boveri and Sutton hypothesized that Mendel’s principles were related to meiosis, they didn’t have any experimental evidence to support their claim. That evidence came in from the lowly fruit fly, Drosophila melanogaster. At the turn of the 20th century, a biologist named Thomas Hunt Morgan began studying the fruit fly with the hopes of understanding inheritance in animals. This was a daunting task because unlike plants, animals can not be self-fertilized. He chose the fruit fly for three main reasons. First, they are really easy to keep alive...just give them fruit! Second, a fruit fly has an extremely short generation time (about 10 days). Data from many generations can be accrued in a relatively short amount of time. Third, fruit flies have a tremendous amount of phenotypic variation.

In his studies, he noticed a fly with a white eye. No one had ever seen a white-eyed fruit fly before (all others had red eyes). He inferred that this was a mutation in the DNA that was expressed in the eye color. He then designed a set of crosses in order to determine how eye color was inherited. 

When a gene is located on a sex chromosome, it is said to be sex-linked. Hunt suggested that males expressing the white-eyed phenotype only need to have a single recessive allele in order to be expressed, if it is on the X chromosome. The Y chromosome does not have a gene that codes for proteins responsible for eye color. Since the white eyed phenotype is a recessive characteristic in flies, he suggested that female flies must have a recessive allele for eye color on both X chromosomes. If this were true he posited that he should be able to predict the phenotypic ratio of controlled crosses, according to Mendel’s principle of segregation.

Results of Boveri and Sutton's discovery of the sex-linked gene for eye color on the X chromosome of Drosophila melanogaster

Results of Boveri and Sutton's discovery of the sex-linked gene for eye color on the X chromosome of Drosophila melanogaster

Gene Linkage and Independent Assortment

Morgan found that his expected phenotypes in the F1 and F2 supported the hypothesis that genes were linked to specific chromosomes. This finding had implications for how genes assort during meiosis. Several genes are linked to a single chromosome, and chromosomes are the ‘particles’ separated during meiosis, not the alleles suggested by Mendel. Therefore, logic indicates that not all genes are independently assorted as predicted by Mendel. Genes on the same chromosome should be linked. In other words, genes on the same chromosome should be dependently assorted (originally rejected by Mendel’s dihybrid crosses), whereas genes on separate chromosomes should be independently assorted (as predicted by Mendel). Linked genes violate independent assortment.

To test this, Morgan discovered another X-linked gene related to body color, with grey bodies as a dominant phenotype (expressed as XB) and yellow bodies as the recessive phenotype (expressed as Xb) . Below are the possible combination of sex, eye color (red = XE ; white = Xe)  and body color: 

Genotype combinations responsible for eye color and body color phenotypes linked to the X chromosomes in Drosophila.   

Genotype combinations responsible for eye color and body color phenotypes linked to the X chromosomes in Drosophila. 

 

Morgan’s results did not support the hypothesis of gene linkage. For example, he expected to find relatively equal proportions of grey-bodied/white-eyed males (XBeY) to yellow-bodied/red-eyed males (XbEY). Do you see that in your Punnett square? Above are his results for males of the XBeXbE x XBeY cross. While the phenotypes representing the genotypes XBeY and XbEY were nearly equally proportionate as predicted. He did not expect to see yellow bodied males at all. But how?

Again, the inner working of meiosis are responsible for Morgan’s results. He suggested that while genes are usually on same chromosome and remain linked during meiosis, but not always. Sometimes alleles on the same chromosomes don’t always stay together. Morgan proposed that during meiosis paired homologous chromosomes can swap segments of chromosomes between them. He referred to these recombined chromosomes (part paternal-part maternal) as recombinant chromosomes.

Further work by Morgan and colleagues supported this hypothesis, and they found that homologous chromosomes do, in fact, recombine during prophase I of meiosis. Morgan termed this process as crossing over, and it involves the physical exchange of the same segments of non-sister chromatids between homologous chromosomes. 

Crossing over in Meiosis explains Morgan's discovery of recombinant chromosomes. Steps in Meiosis - 1: Chromosome duplication; 2: pairing of homologous chromosomes; 3: crossing-over; 4: first division – one of each duplicated chromosome per daughter; 5: second division – one of each chromosome per daughter.

Crossing over in Meiosis explains Morgan's discovery of recombinant chromosomes. Steps in Meiosis - 1: Chromosome duplication; 2: pairing of homologous chromosomes; 3: crossing-over; 4: first division – one of each duplicated chromosome per daughter; 5: second division – one of each chromosome per daughter.

One gene, multiple alleles

Different alleles emerge via mutations during DNA replication, and they occur randomly. Therefore, it is possible for a gene to have more than one allele, and some do. Human blood type is an excellent example of multiple alleles. A gene known as I is responsible for the production of a specific polysaccharide attached to a glycoprotein found in the cellular membrane of red blood cells (Fig. 5). The recessive allele i codes for a base polysaccharide. The alleles IA and IB code for the same base polysaccharide plus an additional sugar added to the end. IA codes for one sugar, while IB codes for a different sugar. 

Phenotypes expressed by the i gene. i codes for a base polysaccharide, while iA and iB code for the base plus a sugar.  

Phenotypes expressed by the i gene. i codes for a base polysaccharide, while iA and iB code for the base plus a sugar.

 

Diagram of ABO blood groups and the antibodies present in each.

Diagram of ABO blood groups and the antibodies present in each.

Codominance

In human ABO blood type there are three blood type phenotypes possible: IAIA, IAIB, IBIB, IAi, IBi, and ii. Understanding these blood types is important in blood transfusions, and it is due to the acceptance of the glycoproteins on the blood cellular membranes coded by the I gene. Similar to Mendelian genetics, i is recessive to both IA and IB. But what happens when both IA and IB alleles are in a gene? As it turns out, both alleles are activated. So blood cells of the genotype IAIB produce different glycoproteins with both sugars. This double expression is known as codominance. 

Incomplete Dominance 

Mendel discovered that when a hybrid is created in the F1 generation, one phenotype is present (dominant) while the other is absent (recessive). In flower color in four-o’clocks, this is not the case. If you cross a pure line purple flower (FPFP) with a pure line white flower (FWFW), you won’t get either purple or white flower in the F1 generation. You get pink flowers!

Incomplete dominance in four-o’clocks.    

Incomplete dominance in four-o’clocks.