The Beginnings of Genomic Biology Classical Genetics

Chapter 2. The beginnings of Genomic Biology – Classical Genetics
Contents

•The beginnings of Genomic Biology – classical genetics

•Mendel & Darwin – traits are conditioned by genes

•Genes are carried on chromosomes

•The chromosomal theory of inheritance

•Additional Complexity of Mendelian Inheritance

•Multiple alleles

•Incomplete dominance and co-dominance

•Sex linked inheritance

•Epistasis

•Epigenetics

•Genes on the Same Chromosome are Linked

•Meiosis: chromosomes assort independently

•Mapping genes on chromosomes

•Quantitative Genetics: Traits that are Continuously Variable

•Population Genetics: Traits in groups of individuals

Chapter 2. The Beginnings of Genomic Biology –Classical Genetics

• Chapter 2. The Beginnings of Genomic Biology –Classical Genetics

It should be clear that the beginings of genomic biology are grounded in classical or Mendelian Genetics. Once the relationship between traits and genes was understood, the relationship between cells and genetics was investigated, leading to the discovery of chromosomes, and a quest for the substance that carried the genetic information began, culminating in the discovery of DNA. These studies constitute the contribution of classical genetics to the founding of the genomic era.

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2.1. Mendel & Darwin –

Traits are conditiondby genes.

2.1. Mendel & Darwin –

Traits are conditiondby genes.

The idea of genomic biology begins with a consideration of what makes up genomes. Specifically what are genes. The timeline of genetics and genomics begins with the early work of Charles Darwin and Gregor Mendel who didn’t really talk about genes per se, but who did describe the behavior of the characteristics of biological organisms, which they referred to as traits.

The idea of genomic biology begins with a consideration of what makes up genomes. Specifically what are genes. The timeline of genetics and genomics begins with the early work of Charles Darwin and Gregor Mendel who didn’t really talk about genes per se, but who did describe the behavior of the characteristics of biological organisms, which they referred to as traits.

Charles Darwin

In 1859 Charles Darwin published his book On the Origin of Species. In this work Darwin described a mass of descriptive support for the concept that “traits” are stably transmitted through subsequent generations, and that organisms that have superior traits survive their natural environment to pass those traits on to the next generation. However, Darwin did not describe any mechanism for such transmission of traits to the next generation.

Experimental evidence for a mechanism explaining how traits pass to subsequent generations came in 1866 when an Austrian monk, Gregor Mendel, published his studies covering 10 years worth of work on the mechanism of inheritance of 7 characteristics in garden peas in a paper called “Experiments in Plant Hybridization”.

In 1859 Charles Darwin published his book On the Origin of Species. In this work Darwin described a mass of descriptive support for the concept that “traits” are stably transmitted through subsequent generations, and that organisms that have superior traits survive their natural environment to pass those traits on to the next generation. However, Darwin did not describe any mechanism for such transmission of traits to the next generation.

Experimental evidence for a mechanism explaining how traits pass to subsequent generations came in 1866 when an Austrian monk, Gregor Mendel, published his studies covering 10 years worth of work on the mechanism of inheritance of 7 characteristics in garden peas in a paper called “Experiments in Plant Hybridization”.

Gregor Mendel

Mendel's Experiments Video

In 1865 Mendel delivered two long lectures that were published in 1866 as "Experiments in Plant Hybridization." This established what eventually became formalized as the Mendelian Laws of inheritance:

•The law of dominance. For each trait, one factor (gene) is dominant and appears as the phenotype in the first filial generation (F1). In the F2 generation the dominant trait occurs more often, in a definite 3:1 ratio. The alternative form is recessive. In Mendel's peas, tallness was dominant, shortness recessive. Therefore, three times as many plants were tall as were short. This constant ratio represents the random combination of alleles during reproduction. Any combination of alleles that includes the dominant allele will express that form of the trait.

In 1865 Mendel delivered two long lectures that were published in 1866 as "Experiments in Plant Hybridization." This established what eventually became formalized as the Mendelian Laws of inheritance:

•The law of dominance. For each trait, one factor (gene) is dominant and appears as the phenotype in the first filial generation (F1). In the F2 generation the dominant trait occurs more often, in a definite 3:1 ratio. The alternative form is recessive. In Mendel's peas, tallness was dominant, shortness recessive. Therefore, three times as many plants were tall as were short. This constant ratio represents the random combination of alleles during reproduction. Any combination of alleles that includes the dominant allele will express that form of the trait.

The law of independent segregation. Inherited characteristics (such as stem length in Mendel's pea plants) exist in alternative forms (tallness, shortness)—today known as alleles. For each characteristic, an individual possesses two paired alleles—one inherited from each parent. Correspondingly, these pairs segregate (i.e. separate or assort) in germ cells and recombine during reproduction so that each parent transmits one allele to each offspring.

•The law of independent assortment. Specific traits operate independently of one another. A pea plant might have a stem that is tall or short, but in either case may produce white or gray seed coats.

However, the significance of Mendel’s work and his insight into the mechanism of inheritance went unrecognized until 1900 when three European scientists, Hugo de Vries, Carl Correns, and Erich von Tschermak reached similar conclusions in their own research though they claimed to be unaware of Mendel’s earlier theory of the 'discrete units' on which genetic material resides.

The biological entity (factor) responsible for defining traits was later termed a gene by Wilhelm Johansen in 1910, but the biological basis for inheritance remained unknown until DNA was identified as the genetic material in the 1940s. Thus,

•The law of independent segregation. Inherited characteristics (such as stem length in Mendel's pea plants) exist in alternative forms (tallness, shortness)—today known as alleles. For each characteristic, an individual possesses two paired alleles—one inherited from each parent. Correspondingly, these pairs segregate (i.e. separate or assort) in germ cells and recombine during reproduction so that each parent transmits one allele to each offspring.

•The law of independent assortment. Specific traits operate independently of one another. A pea plant might have a stem that is tall or short, but in either case may produce white or gray seed coats.

However, the significance of Mendel’s work and his insight into the mechanism of inheritance went unrecognized until 1900 when three European scientists, Hugo de Vries, Carl Correns, and Erich von Tschermak reached similar conclusions in their own research though they claimed to be unaware of Mendel’s earlier theory of the 'discrete units' on which genetic material resides.

The biological entity (factor) responsible for defining traits was later termed a gene by Wilhelm Johansen in 1910, but the biological basis for inheritance remained unknown until DNA was identified as the genetic material in the 1940s. Thus,

it was early in the 20th century that the name “gene” was given to the hereditary unity described by Mendel decades earlier, and the study of genetics and genomics began in earnest.

it was early in the 20th century that the name “gene” was given to the hereditary unity described by Mendel decades earlier, and the study of genetics and genomics began in earnest.

2.2. Genes are Carried on Chromosomes.

2.2. Genes are Carried on Chromosomes.

At about the same time that genes were coming into focus as having a role in inheritance, a series of observations at the cellular level established:

•The existence of structures called chromosomes.

At about the same time that genes were coming into focus as having a role in inheritance, a series of observations at the cellular level established:

•The existence of structures called chromosomes.

•Chromosomes carry genes.

The notion that Mendel’s particulate hereditary factors reside on visible structures called chromo-somes was originally independently proposed by Theodor Boveri, a German scientist, and Walter Sutton, an American graduate student, in 1902 at about the same time that Mendel’s Laws of inheritance were being rediscovered.

The developing theory stated:

•More than one gene is located on each chromosome.

Thus, chromosomes are like a string of beads with each gene represented as a bead. Along the length of the chromosome (string of beads) there are genes for many traits on each chromosome, and each gene occupies a specific position on each chromosome called a locus.

•The chromosomes are passed from one generation to the next and carry genes to the next generation as they are passed.

These points were incorportated into what we now know as the Chromosomal Theory of Inheritance.

The developing theory stated:

•More than one gene is located on each chromosome.

Thus, chromosomes are like a string of beads with each gene represented as a bead. Along the length of the chromosome (string of beads) there are genes for many traits on each chromosome, and each gene occupies a specific position on each chromosome called a locus.

•The chromosomes are passed from one generation to the next and carry genes to the next generation as they are passed.

These points were incorportated into what we now know as the Chromosomal Theory of Inheritance.

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2.3. The Chromosomal Theory of Inheritance.

2.3. The Chromosomal Theory of Inheritance.

In the early years of the 20th century Thomas Hunt Morgan, who was skeptical about the theories of the day concerning Mendel’s observations and the role of chromosomes in inheritance, began conducting a series of experiments using the fruit fly, Drosophilla melanogaster, that ultimately convinced him of the details of inheritance leading to what is called today the chromosomal theory of inheritance. The general tenets of this theory are given below:

•Multiple genes conditioning the cellular and organismal traits an organism possesses are passed from one cellular or organismal generation to the next on chromosomes.

•Genes for specific traits reside at specific positions on chromosomes called loci (singular locus).

•Most cells of an organism have homologous pairs of chromosomes for each chromosome found in the cell.

•The complete set of chromosomes an organism possesses is called it’s karyotype.

In the early years of the 20th century Thomas Hunt Morgan, who was skeptical about the theories of the day concerning Mendel’s observations and the role of chromosomes in inheritance, began conducting a series of experiments using the fruit fly, Drosophilla melanogaster, that ultimately convinced him of the details of inheritance leading to what is called today the chromosomal theory of inheritance. The general tenets of this theory are given below:

•Multiple genes conditioning the cellular and organismal traits an organism possesses are passed from one cellular or organismal generation to the next on chromosomes.

•Genes for specific traits reside at specific positions on chromosomes called loci (singular locus).

•Most cells of an organism have homologous pairs of chromosomes for each chromosome found in the cell.

•The complete set of chromosomes an organism possesses is called it’s karyotype.

Figure 2.1. The complete set of 23 pairs of human chromosomes is shown in the karyotype above. Note that there are 22 pairs of autosomal Chromosomes, and the X and Y sex chromosome “pair”. Thus, we say that there are 22 pairs of homologous autosomal chromosomes plus a pair of sex chromosomes (X or Y) in humans, and humans have 46 (diploid number) chromosomes in total.

Figure 2.1. The complete set of 23 pairs of human chromosomes is shown in the karyotype above. Note that there are 22 pairs of autosomal Chromosomes, and the X and Y sex chromosome “pair”. Thus, we say that there are 22 pairs of homologous autosomal chromosomes plus a pair of sex chromosomes (X or Y) in humans, and humans have 46 (diploid number) chromosomes in total.

The complete set of human chromosomes is shown in Figure 2.1. Humans have 22 pairs of autosomal chromosomes, and the X and Y sex chromosomes that are present in males (XY) of females (XX). Thus, we say that there are 22 pairs of homologous autosomal chromosomes plus a pair of sex chromosomes (X or Y) in humans. Humans have 46 chromosomes in total, and the diploid number of chromosomes is 26.

The complete set of human chromosomes is shown in Figure 2.1. Humans have 22 pairs of autosomal chromosomes, and the X and Y sex chromosomes that are present in males (XY) of females (XX). Thus, we say that there are 22 pairs of homologous autosomal chromosomes plus a pair of sex chromosomes (X or Y) in humans. Humans have 46 chromosomes in total, and the diploid number of chromosomes is 26.

Gametes, eukaryotic cells that pass chromosomes to the next organismal generation, contain only a haploid number of chromosomes (23 in the case of homans). Thus, gametes have only 1 chromosome from each pair found in a non-gametic cell. Chromosome numbers are constant for a species, but vary from one species to another.

•One of the chromosomes in each homologous pair comes from the maternal parent while the other chromosome in the pair comes from the paternal parent.

•Although traits are conditioned by genes at specific loci on the chromosomes, the gene at a given locus coming from each parent may not be the same. They can be either the dominant (according to Mendel’s law of dominance) factor, ort he recessive factor. We now call the nature of the factor (gene) at each locus, an allele.

•When both the maternal and paternal homologous chromosome contain the same allele, the organism is said to be homozygous, but if the alleles contained at the locus on the homologous chromosomes are different the organism is said to be heterozygous.

•When an organism is homozygous, if the allele it bears is the dominant allele, the organism demonstrates a homozygous dominant genotype. While a homozygous organism bearing 2 identical recessive alleles is considered homozygous recessive genotype.

Gametes, eukaryotic cells that pass chromosomes to the next organismal generation, contain only a haploid number of chromosomes (23 in the case of homans). Thus, gametes have only 1 chromosome from each pair found in a non-gametic cell. Chromosome numbers are constant for a species, but vary from one species to another.

•One of the chromosomes in each homologous pair comes from the maternal parent while the other chromosome in the pair comes from the paternal parent.

•Although traits are conditioned by genes at specific loci on the chromosomes, the gene at a given locus coming from each parent may not be the same. They can be either the dominant (according to Mendel’s law of dominance) factor, ort he recessive factor. We now call the nature of the factor (gene) at each locus, an allele.

•When both the maternal and paternal homologous chromosome contain the same allele, the organism is said to be homozygous, but if the alleles contained at the locus on the homologous chromosomes are different the organism is said to be heterozygous.

•When an organism is homozygous, if the allele it bears is the dominant allele, the organism demonstrates a homozygous dominant genotype. While a homozygous organism bearing 2 identical recessive alleles is considered homozygous recessive genotype.

The genotype that an organism possesses in combination with environmental factors is responsible for production of the trait that we see. This is also a definition of the phenotype of an individual, i.e. the appearance of the individual resulting from the interaction of genotype and environmental factors. Thus, an organism can demonstrate a dominant phenotype or a recessive phenotype.

What Mendel observed was the phenotype of his pea plants. From observations of phenotype he proposed a model for genotypic behavior of his “factors” that we no know as genes. We also know that these genes reside on chromosomes, and the manner in which the chromosomes are passed to the next generation provides the basis for Mendel’s law of segregation that directly relates the behavior of the chromosomes bearing the genes to the phenotypic behavior that Mendel observed. However, there are a number of instances where, although Mendel’s law of segregation applies additional background is required to appreciate how such Mendel’s work applies.

•The genotype that an organism possesses in combination with environmental factors is responsible for production of the trait that we see. This is also a definition of the phenotype of an individual, i.e. the appearance of the individual resulting from the interaction of genotype and environmental factors. Thus, an organism can demonstrate a dominant phenotype or a recessive phenotype.

What Mendel observed was the phenotype of his pea plants. From observations of phenotype he proposed a model for genotypic behavior of his “factors” that we no know as genes. We also know that these genes reside on chromosomes, and the manner in which the chromosomes are passed to the next generation provides the basis for Mendel’s law of segregation that directly relates the behavior of the chromosomes bearing the genes to the phenotypic behavior that Mendel observed. However, there are a number of instances where, although Mendel’s law of segregation applies additional background is required to appreciate how such Mendel’s work applies.

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Figure 2.2. Phenotypic description of the alleles of the C-locus for coat color in rabbits. Note that this patterning is also found in many other animals although the names of the phenotypes may differ.

Figure 2.2. Phenotypic description of the alleles of the C-locus for coat color in rabbits. Note that this patterning is also found in many other animals although the names of the phenotypes may differ.

2.4.1. Multiple alleles (retrun)

Note that it is possible that for some traits more than 2 alleles exist. In this case there is a hierarchy of dominance among the multiple alleles. In any given individual the more dominant allele of the 2 alleles it posses is dominant, while the more recessive one will be the recessive allele.