Gregor Mendel, the pioneer of modern genetics, began investigating inheritance in 1843, long before chromosomes were observed under a microscope. Cell biologists may use dyes to stain and detect subcellular structures and examine their actions during cell division and meiosis, thanks to advancements in microscopic techniques in the late 1800s.
Chromosomes are duplicated, condensed from an amorphous (non-uniform) nuclear mass into unique X-shaped entities (pairs of identical sister chromatids), and moved to separate cellular poles with each mitotic division.
Mendel and His Work on Genetics
Mendel published the first-ever findings on the theory of inheritance in 1865, but for a variety of reasons, it was not acknowledged until 1900.
To start with, communication was tough in those days, and his research could not have been made available to the public.
Second, Mendel’s notions of genes and alleles was not approved by his contemporaries as an understanding for the seemingly continuous variation seen in nature. According to him, genes were stable and discrete units and a pair of alleles do not mix with each other.
Third, Mendel’s notion of using math to describe biological processes was revolutionary at the time, and many scientists were dubious. Finally, even though Mendel’s study implied that factors (genes) were discrete units, he was unable to provide any physical evidence for their existence or specify what they were constituted of.
1. History of Mendelian Inheritance
Mendel planted and tested 5,000 pea plants in his monastery’s garden between 1856 and 1863.
He generated two generalizations from these results, which later became known as Mendelian inheritance.
He documented his studies in a two-part paper titled “Experiments on Plant Hybridization,” which he gave to the Natural History Society of Brno on February 8 and March 8, 1865, but which was not published until 1866.
Despite the widespread acceptance of Darwin’s notion of continuous variation, unknown chromosomal behavior and phenomenon of fertilization, and certain mathematical calculation and probability rule, Mendel’s results were completely ignored by the vast majority.
1.1. Mendel’s Laws of Inheritance:
1.1.1 The Law of Segregation: A pair of gene define every inherited trait. Familial genes are randomly distributed to sex cells, with each sex cell containing only one of the pair’s genes. When sex cells join in fertilization, offspring acquire one gene from each parent.
1.1.2. The Law of Independent Assortment: Genes for different characteristics are sorted independently from one another so that the inheritance of one feature is unaffected by the inheritance of another.
1.1.3. The Law of Dominance: When there are many variants of a gene in a species, the dominant form is expressed.
2. Chromosomal Theory of Inheritance
Three scientists (de Vries, Correns, and von Tschermak) independently rediscovered Mendel’s findings on character inheritance in 1900 and marked the discovery of the Chromosomal theory of inheritance.
Scientists were also able to closely study cell division during this period thanks to advances in microscopy. Even so, until William Bateson, who also invented the terms genetics and allele, popularized the discoveries, many people were unsure whether they could be applied to all species.
Later research by biologists and statisticians like Ronald Fisher showed that if several Mendelian factors were involved in the expression of a single characteristic, they might create the various results observed, demonstrating that Mendelian genetics is consistent with natural selection.
As a result, regions in the nucleus that appeared to double and divide right before the process of each cell division were discovered.
These were referred to as chromosomes (colored bodies, as they were visualized by staining). Walter Sutton and Theodor Boveri were credited with developing the notion of chromosomal movement during meiosis, and that chromosomal behavior mirrored that of genes, and they used chromosome mobility to explain Mendel’s rules.
Thomas Hunt Morgan and his collaborators combined Mendel’s computational foundation with the chromosome theory of inheritance, wherein the chromosomes of cells were thought to contain the actual hereditary material, and proposed classical genetics, an extremely successful foundation that cemented Mendel’s place in history.
The Chromosomal Theory of Inheritance was backed by the following observations that were consistent with Mendel’s laws:
Homologous chromosome pairs migrate as distinct structures separate from other chromosome pairs during meiosis.
The sorting of chromosome pairs into pre-gametes from each homologous pair appears to be random.
From each parent, only half of their chromosome complement is incorporated into gametes.
Despite the fact that male and female gametes (sperm and egg) differ in size and shape, they both have the same number of chromosomes, implying that each parent contributed equal genetic material hence proving the chromosomal theory of inheritance.
During fertilization, the gametic chromosomes join to produce offspring with the same chromosomal number as their parents. Others were only tangentially related (showed higher recombination).
Chromosomal theory of inheritance states that the pairing and separation of a pair of chromosomes, according to Sutton and Boveri, would result in the segregation of a pair of factors they carried. The chromosomal theory of inheritance was created by Walter Sutton, who combined his knowledge of chromosomal segregation with Mendelian concepts.
Following this convergence of concepts, Thomas Hunt Morgan and his colleagues used experimental verification of the chromosomal theory of inheritance to discover the basis for the variation produced by sexual reproduction. Morgan studied with Drosophila melanogaste, a little fruit fly that has been proven to be ideal for such research.
These fruit flies are cultivated in the lab on simple synthetic media. They have a two-week life cycle and can produce a huge number of offspring flies from a single mating. The fruit flies also have easily distinguishable sexes, making it much easier to study them.
4. Genes Are Located On Chromosomes
We assume that DNA is the genetic material and that our genes must consequently be found on chromosomes. But, like all scientific facts, this notion had to be repeatedly tested and shown correctly before being recognized as fact.
Based on tests with Drosophila melanogaster, or fruit flies, Thomas Hunt Morgan proposed the chromosomal theory of inheritance or the assumption that genes are located on chromosomes.
These fruit flies are similar to humans in that those with two X chromosomes are female, while those with one X and one Y chromosome are male (many organisms have other ways of determining gender).
Drasophila has a dominant eye-color of red. Morgan uncovered an allele (recessive mutation) that causes white eyes. Morgan mated a red-eyed female with a white-eyed male to produce offspring with red-eyed with a dominant/recessive inheritance structure. This finding made perfect sense.
On the other hand, Morgan received an unexpected result when he mated the male and female fruit fly, i.e., white-eyed females, to red-eyed males in a reciprocal cross.
He saw that instead of all red-eyed offspring, all females had red eyes and all males had white eyes. Because two distinct qualities (gender and eye color) appeared to be related, this result appeared to violate Mendel’s concept of independent assortment.
Only if the gene that influenced eye color was situated on (related to), the X chromosome could these results be explained.
The only way to explain this data is if the eye color gene is on the X chromosome, they support the chromosome theory of inheritance. This is known as sex-linkage, or the inheritance of genes from both sexes’ chromosomes (X and Y).
Because females have two copies of each X chromosome, but males only have one, sex-related features have unique inheritance patterns.
Because he only has one copy of the recessive gene, a male with the recessive allele will always manifest the recessive trait. Most genes, on the other hand, are found on the autosomes, or non-sex chromosomes, where each gene is duplicated in both males and females.
The Chromosomal Theory of Inheritance states that the action of chromosomes during meiosis explains all of Mendel’s inheritance patterns, including the principle of segregation and the principle of independent assortment.
5. Linkage and Recombination
The Chromosomal Theory of Inheritance states that the theory of linkage is the inheritance of features in a way that defies Mendel’s principle of independent assortment, which states that alleles for different traits should be segregated into gametes separately.
Traits are associated with sex chromosomes in a unique sort of linkage termed as sex-linkage. When the genes that govern two separate qualities are close to one another on the same chromosome, genetic linkage occurs.
The basic principle of the Chromosomal Theory of Inheritance is that if two genes are located on the same chromosome, and you inherit the entire chromosome, you must inherit those two genes (and whatever alleles they include) together.
However, because this is biology, there is a catch: Chromosomal Theory of Inheritance states that the phenomenon of crossing over aids in the shuffle of alleles for genes on the same chromosome.
Genetic recombination, or new combinations of alleles on a chromosome, is caused by a crossover event between the sites of two genes on a chromosome.
It may come as a surprise to discover that genes on the same chromosome may assort independently (as if they were on different chromosomes) if they are distanced enough that a crossover almost always occurs, culminating in 50% recombinants (because crossing over involves only two of the 4 chromatids in a synapsed pair of homologous chromosomes, the maximum recombination frequency is 50 percent).
Thomas Hunt Morgan used Drosophila to conduct multiple dihybrid crossings to investigate sex-linked genes.
Chromosomal Theory of Inheritance states that the crosses were similar to the idea of Mendel’s pea dihybrid crosses. Morgan, for example, intercrossed the F1 progeny of yellow-bodied, white-eyed females with brown-bodied, red-eyed males.
He noticed that the two genes did not segregate independently of one another and that the F2 ratio was notably different from the 9:3:3:1 ratio (expected when the two genes are independent).
Morgan and his associates knew the behavior of chromosomes and the Chromosomal Theory of Inheritance during meiosis and that the genes were on the X chromosome, and they noticed right away that when the genes in a dihybrid cross were on the same chromosome, the fraction of parental gene combinations were substantially higher than the non-parental kind.
While working on this theory of inheritance, Morgan attributed this to the physical relationship or linkage of the two genes, coining the terms linkage and recombination to characterize this physical association of genes on a chromosome and the production of non-parental gene combinations, respectively.
While working on the Chromosomal Theory of Inheritance, Morgan and his colleagues also discovered that even when genes were grouped on the same chromosome, some were firmly coupled (with little recombination via the homologous chromosomes), and others were loosely linked (showed higher recombination).
Chromosomal Theory of Inheritance states that the exchange of genetic material between several chromosomes or different areas of the same chromosome is known as DNA recombination.
Homology is usually involved in this process; homologous chromosome sections line up in preparation for transfer, and some level of sequence identity is required.
However, there are some occurrences of non – homologous recombination exchange of genetic data between newly multiplied chromosomes during meiosis is an essential example of crossover in diploid eukaryotic animals.
Chromosomal Theory of Inheritance states that each gamete contains both maternal and paternal genetic material, allowing the eventual offspring to acquire genes from all four of their grandparents, resulting in the greatest genetic variety possible.
Experiments with maize were the first to illustrate the importance of recombination in chromosomal inheritance. Barbara McClintock and Harriet Creighton discovered evidence for recombination in maize chromosomes by physically tracing an odd knob structure through numerous genetic crosses in 1931.
The scientists were able to establish that some alleles were physically related to the knobbed chromosome, while others were tied to the regular Chromosomal Theory of Inheritance, using a maize strain in which one member of a chromosomal pair exhibited the knob, but its counterpart did not.
Following these alleles through meiosis, McClintock and Creighton discovered that alleles for certain phenotypic features were physically swapped between chromosomes according to this Chromosomal Theory of Inheritance.
6. Pedigree Analysis
We can’t invite different individuals to mate and generate a large number of offspring in order to investigate human inheritance patterns. In order to infer inheritance patterns, we rely on pedigree analysis.
A pedigree chart displays a family tree in which the family members impacted by a particular genetic trait are depicted. Gene ramming and gene expressivity can also be estimated via pedigree analysis.
Penetrance refers to the likelihood that a disease may manifest in a person who contains an allele indicating that the disease is suspected.
For instance, if one-half of all people who carry a dominant gene eventually develop the disease, the gene has a 50% penetrance. The spectrum of symptoms and severity associated with various illness states is referred to as expressivity.
Males are symbolized by squares, whereas females are symbolized by circles.
Each person is represented by a Roman Numeral that indicates the family’s generation and a Digit that symbolizes the person within that generation.
A male and female joined by a horizontal line have mated and given birth to children.
Parents and their offspring are linked by vertical lines.
An individual impacted by the trait is represented by a darkened circle or square.
6.2. Rules of Pedigree Analysis
6.2.1. Autosomal Recessive:
- Both males and females are equally affected
- Alleles are generated from each parent
- The sperm and egg may just be carriers
- ~1/4 of children affected
6.2.2. Autosomal Dominant:
- Both males and females are equally affected
- Just one parent should carry the allele
- If a child exhibits characteristics, at least one parent must also display the same characteristic
6.2.3. X-linked Recessive:
- Usually only affects males
- Affected males transmit alleles to daughters, not sons.
- Characteristic skips a generation
6.3. Key Points:
When it comes to pedigrees, there are five factors to keep in mind.
(1) A person who is unaffected cannot have any dominant characteristic alleles.
(Because an individual is affected by a single gene of a dominant characteristic).
(2) Individuals entering into the family are believed to have no disease alleles, meaning they will never be impacted by recessive traits and will never be carriers.
(because of the rarity of the character in the population)
(3) A person who is unaffected can be a recessive trait carrier (carry one allele).
(Because a recessive trait requires two alleles for one individual to be impacted)
(4) When a trait is X-linked, a single recessive gene can affect a male.
(Because the man is hemizygous for an X-linked characteristic, he only has one allele)
(5) A father’s X-linked gene allele is passed down to his daughters but not to his sons.
Both children and sons inherit an allele of X-linked genes from their mother.
Once the disorder’s inheritance pattern has been established, the position of relatives in the lineage can be assessed according to the Inheritance Chromosomal theory.
Mutation carriers can be detected by carefully monitoring the position of individuals affected. The risk of diseases for additional family members or the likelihood that a couple will have an afflicted kid can be assessed using this information.
Many animals have pedigrees as well, albeit the objective of the pedigree analysis is slightly different. The pedigree data is typically used to identify individuals with specified characteristics for breeding purposes.
Unfavourable traits are eliminated from consideration in order for the following generation to include more individuals with desirable traits. Characters of choice will differ depending on the species. Pedigree analysis in the thoroughbred world aims to blend speed, stamina, and a desire to win to produce winning racehorses.
High milk output, stronger muscle content, and better wool are desired traits in cows, sheep, and pigs. Researchers are trying to find drought and pest-resistant species with excellent crop yields; thus, even plants have pedigrees.
Pedigree analysis is an important aspect of a thorough medical workup for a hereditary condition in medicine.
The information gathered is crucial to comprehending the issue and offering the best possible counselling to the family. Pedigree analysis is also beneficial for other plant and animal species, albeit the purpose is usually gene selection rather than risk assessment.
-Edited by Steffy Michael|5/7/22