Chapter 15 The Chromosomal Basis of Inheritance

Early Days of Genetics  Pre 1900, geneticists and cytologists studied mitosis and meiosis.  In 1900, scientists in the two fields began to see parallels between the behavior of chromosomes and Mendel’s “heredity factors” during the sexual life cycle.  Pre 1900, geneticists and cytologists studied mitosis and meiosis.  In 1900, scientists in the two fields began to see parallels between the behavior of chromosomes and Mendel’s “heredity factors” during the sexual life cycle.

Early Days of Genetics  Walter Sutton and Theodore Boveri and others working independently began to recognize the parallels.  The things they noticed were:  Chromosomes and genes are present in pairs in diploid cells.  Homologous chromosomes separate and alleles segregate during the process of meiosis.  Fertilization restores the paired conditions for both chromosomes and genes.  The chromosomal theory of inheritance began to take shape.  Walter Sutton and Theodore Boveri and others working independently began to recognize the parallels.  The things they noticed were:  Chromosomes and genes are present in pairs in diploid cells.  Homologous chromosomes separate and alleles segregate during the process of meiosis.  Fertilization restores the paired conditions for both chromosomes and genes.  The chromosomal theory of inheritance began to take shape.

The Chromosomal Theory of Inheritance  This theory suggested that:  Mendelian genes have specific loci on chromosomes.  Chromosomes undergo segregation and independent assortment.  This theory suggested that:  Mendelian genes have specific loci on chromosomes.  Chromosomes undergo segregation and independent assortment.

Thomas Hunt Morgan  Initially, Morgan was skeptical about the chromosomal theory of inheritance and Mendelism. However, his results proved otherwise.  Around 1906, Morgan began to piece together the first solid evidence associating specific genes with specific chromosomes.  Initially, Morgan was skeptical about the chromosomal theory of inheritance and Mendelism. However, his results proved otherwise.  Around 1906, Morgan began to piece together the first solid evidence associating specific genes with specific chromosomes.

Morgan’s Organism of Study  Morgan chose the fruit fly (Drosophila melanogaster) for its ease of use, heartiness, and prolific breeding habits.

Drosophila melanogaster  Another thing making the fruit flies an ideal tool for study is that they only have 4 chromosomes (3 pairs of autosomes and 1 pair of sex chromosomes--Females XX; Males XY).  One drawback: there were no suppliers of fruit flies so he had to capture and breed his own.  Another thing making the fruit flies an ideal tool for study is that they only have 4 chromosomes (3 pairs of autosomes and 1 pair of sex chromosomes--Females XX; Males XY).  One drawback: there were no suppliers of fruit flies so he had to capture and breed his own.

White Eyed “Mutants”  After about a year of breeding and studying, Morgan found a white eyed fly (normal eye color is red).  This eye color was due to a mutation and is known as the mutant phenotype.  Morgan and his students invented a notation that is still used today to denote a mutant--a lowercase letter, w.  Writing the lowercase letter with a “+,” (w + ) superscript denotes the wild type phenotype.  After about a year of breeding and studying, Morgan found a white eyed fly (normal eye color is red).  This eye color was due to a mutation and is known as the mutant phenotype.  Morgan and his students invented a notation that is still used today to denote a mutant--a lowercase letter, w.  Writing the lowercase letter with a “+,” (w + ) superscript denotes the wild type phenotype.

Experiments With the Mutant  Morgan immediately mated the white eyed male with a red eyed female and found all of the F1 offspring have red eyes--suggesting that red is the dominant allele.

Experiments With the Mutant  He also found that when mating the F1 generation, the F2 exhibited the 3:1 ratio of red eyes to white eyes, but only males had white eyes, and they were present in a 50/50 ratio of red to white.

Morgan’s Conclusion:  Somehow the eye color of the fly is linked to its sex. (If not, 1/2 of the white eyed offspring would have been male, the other half would have been female).  Since females are XX and males are XY, he concluded that the gene for eye color must be located on the X chromosome, with no corresponding gene on the Y chromosome.  Somehow the eye color of the fly is linked to its sex. (If not, 1/2 of the white eyed offspring would have been male, the other half would have been female).  Since females are XX and males are XY, he concluded that the gene for eye color must be located on the X chromosome, with no corresponding gene on the Y chromosome.

Morgan’s Reasoning and Analysis:  In a male fly, having a single copy of the mutant allele would give the mutant trait-- white eyes. Since females have 2 X chromosomes and all of the F1 males have red eyes, there is no way for the females to have white eyes in this generation.

In Support of Sex Linkage  This finding lent support to the chromosomal theory of inheritance--a specific gene is carried on a specific chromosome.  It also provided data regarding sex linkage. That is, genes located on the sex chromosomes exhibit unique inheritance patterns and unique ratios in the offspring.  This finding lent support to the chromosomal theory of inheritance--a specific gene is carried on a specific chromosome.  It also provided data regarding sex linkage. That is, genes located on the sex chromosomes exhibit unique inheritance patterns and unique ratios in the offspring.

Sex-Linkage Continued…  Now that you know a little about sex linkage, most sex-linked genes are only found on the X chromosome.  Females can pass such a disorder (gene) on to both male and female offspring.  Males can only pass a disorder (gene) on to daughters only.  Now that you know a little about sex linkage, most sex-linked genes are only found on the X chromosome.  Females can pass such a disorder (gene) on to both male and female offspring.  Males can only pass a disorder (gene) on to daughters only.

Sex-Linkage Continued…  Sex linked recessives are only displayed in females when they are inherited in the homozygous condition.  Males display the trait when they inherit one copy of the gene (said to be hemizygous).  Color blind example.  Sex linked recessives are only displayed in females when they are inherited in the homozygous condition.  Males display the trait when they inherit one copy of the gene (said to be hemizygous).  Color blind example.

Linkage  Some genes are said to be sex linked.  Others are simply said to be linked. They are on autosomes.  They are inherited together with other genes and the results of breeding experiments lead to results different from those predicted by Mendel’s law of independent assortment.  Some genes are said to be sex linked.  Others are simply said to be linked. They are on autosomes.  They are inherited together with other genes and the results of breeding experiments lead to results different from those predicted by Mendel’s law of independent assortment.

Morgan’s Evidence of Linkage  Morgan used more mutant traits that he discovered.  Normal fruit flies have gray bodies and normal wings.  2 mutants he noticed had black (b) bodies and vestigial wings (vg).  It was known that these mutations are autosomal and recessive.  He didn’t know if the traits were on the same or different chromosomes, however.  Morgan used more mutant traits that he discovered.  Normal fruit flies have gray bodies and normal wings.  2 mutants he noticed had black (b) bodies and vestigial wings (vg).  It was known that these mutations are autosomal and recessive.  He didn’t know if the traits were on the same or different chromosomes, however.

To Determine Where the Alleles for these Traits Were…  Morgan crossed flies until he got true- breeding wild-type flies and true- breeding double mutant flies for black bodies and vestigial wings.  He could now perform a series of crosses to see if the alleles for these traits were on the same chromosomes or were on different ones.  Morgan crossed flies until he got true- breeding wild-type flies and true- breeding double mutant flies for black bodies and vestigial wings.  He could now perform a series of crosses to see if the alleles for these traits were on the same chromosomes or were on different ones.

His First Cross…  He crossed the homozygous wild-type fly with the double mutant (homozygous recessive) and got a heterozygote.  Remember, both true breeding flies produce only one type of gamete, so a heterozygote in the F1 is assured.  He crossed the homozygous wild-type fly with the double mutant (homozygous recessive) and got a heterozygote.  Remember, both true breeding flies produce only one type of gamete, so a heterozygote in the F1 is assured.

Are they on the Same Chromosome?  Next, he performed a cross of the hybrid F1 offspring with another double mutant.  If the genes were on different chromosomes, then 4 different types of offspring would be seen in a 1:1:1:1 ratio.  Next, he performed a cross of the hybrid F1 offspring with another double mutant.  If the genes were on different chromosomes, then 4 different types of offspring would be seen in a 1:1:1:1 ratio.

If they are on the Same Chromosome…  If they are on the same chromosome and no crossing over occurs, then we should see a 1:1 ratio of the parental phenotypes.

If they are on the Same Chromosome…  If we do see some crossing over and the genes are very close together, most of the offspring will look like the parents.  Some, however, will be recombinants.  This is exactly what Morgan saw!  If we do see some crossing over and the genes are very close together, most of the offspring will look like the parents.  Some, however, will be recombinants.  This is exactly what Morgan saw!

Crossing Over…  The whole idea of crossing over came from these experiments that Morgan performed. From the results, he reasoned that since the numbers didn’t fit what was supposed to be happening, something else must be occurring.  He reasoned that somehow a physical breakage must be occurring between the homologous chromosomes, something we now call “crossing over.”  The whole idea of crossing over came from these experiments that Morgan performed. From the results, he reasoned that since the numbers didn’t fit what was supposed to be happening, something else must be occurring.  He reasoned that somehow a physical breakage must be occurring between the homologous chromosomes, something we now call “crossing over.”

Additional Things to Come From These Experiments…  The idea of a linkage map using the recombination frequencies of genes.  Determination of the order of genes.  Gene mapping to determine where the genes were located.  The idea of a linkage map using the recombination frequencies of genes.  Determination of the order of genes.  Gene mapping to determine where the genes were located.

Crossing Over and Gene Mixing  Crossing Over Crossing Over  Crossing Over Crossing Over

Sex Determination  Whether or not a person is male or female is determined from their genotype: XX is female; XY is male.  In humans, the father determines the sex of the baby.  The chance of being a male or female is 50/50. Half of the sperm will inherit a Y, the other half will inherit the X.  Whether or not a person is male or female is determined from their genotype: XX is female; XY is male.  In humans, the father determines the sex of the baby.  The chance of being a male or female is 50/50. Half of the sperm will inherit a Y, the other half will inherit the X.

Sex Determination and the Y Chromosome  The Y chromosome contains a region (SRY gene) which codes for proteins that induce the gonads to form testes.  In the absence of this protein, the gonads form ovaries.  The Y chromosome contains a region (SRY gene) which codes for proteins that induce the gonads to form testes.  In the absence of this protein, the gonads form ovaries.

Sex Determination and the X Chromosome  Inheriting an X chromosome from dad will give a female 2 X chromosomes.  Only one functions within the cell, the other is inactivated.  It becomes a Barr body.  The Barr body becomes reactivated in gametes so all of them have an active X chromosome when produced.  Inheriting an X chromosome from dad will give a female 2 X chromosomes.  Only one functions within the cell, the other is inactivated.  It becomes a Barr body.  The Barr body becomes reactivated in gametes so all of them have an active X chromosome when produced.

X Inactivation  This process is a totally random event and occurs independently in embryonic cells at the time of X inactivation.  Females consist of a mosaic of active X genes--those derived from the father and those derived from the mother.  This process is a totally random event and occurs independently in embryonic cells at the time of X inactivation.  Females consist of a mosaic of active X genes--those derived from the father and those derived from the mother.

X Inactivation  As the embryo continues to divide mitotically, we now have groups of cells with active X chromosomes derived from the mom, and active X chromosomes derived from dad.  If a female is heterozygous for a sex linked trait, approximately 1/2 of the cells will express one gene, and 1/2 will express the other gene.  As the embryo continues to divide mitotically, we now have groups of cells with active X chromosomes derived from the mom, and active X chromosomes derived from dad.  If a female is heterozygous for a sex linked trait, approximately 1/2 of the cells will express one gene, and 1/2 will express the other gene.

X Inactivation and Mosaicism  X inactivation can be seen in calico cats.  It can also be seen in a sweat gland disorder.  X inactivation can be seen in calico cats.  It can also be seen in a sweat gland disorder.

Nondisjunction  Normally, in meiosis, the chromosomes are distributed without fail and the numbers of chromosomes remains the same throughout the generations.  Occasionally, chromosomes don’t get separated properly in meiosis I or II.  Some gametes fail to receive a copy of a chromosome; others receive 2 copies.  Normally, in meiosis, the chromosomes are distributed without fail and the numbers of chromosomes remains the same throughout the generations.  Occasionally, chromosomes don’t get separated properly in meiosis I or II.  Some gametes fail to receive a copy of a chromosome; others receive 2 copies.

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Aneuploidy  When nondisjunction occurs and is followed by fertilization, a situation arises where an abnormal number of chromosomes are present in the developing organism.

Aneuploidy  A cell with triple the number of a chromosomes is known as trisomy.  Trisomy 21 or Down Syndrome is an example.  Having only one copy of the cell produces a situation known as monosomy.  A cell with triple the number of a chromosomes is known as trisomy.  Trisomy 21 or Down Syndrome is an example.  Having only one copy of the cell produces a situation known as monosomy.

Nondisjunction and Mitosis  Nondisjunction occurs in mitosis too.  If it occurs very early on, then the organism, if it survives, will likely have a large number of phenotypic abnormalities.  Nondisjunction occurs in mitosis too.  If it occurs very early on, then the organism, if it survives, will likely have a large number of phenotypic abnormalities.

Chromosomal Alterations  1. Deletion--a gene or base pair is lost.  2. Duplication--a segment of DNA gets repeated.  3. Inversion--occurs when a chromosomal fragment flip-flops and reattaches to the original chromosome.  4. Translocation--occurs when a fragment from one chromosome is lost and becomes attached to another chromosome.  1. Deletion--a gene or base pair is lost.  2. Duplication--a segment of DNA gets repeated.  3. Inversion--occurs when a chromosomal fragment flip-flops and reattaches to the original chromosome.  4. Translocation--occurs when a fragment from one chromosome is lost and becomes attached to another chromosome.

Deletions and Duplications  Occur most often during meiosis because of crossing over.

Duplications and Translocations  These don’t alter the balance of genes, but the order on the chromosome is disrupted.  This effects the neighboring genes and the expression of the duplicated/translocated genes.  They are usually lethal.  These don’t alter the balance of genes, but the order on the chromosome is disrupted.  This effects the neighboring genes and the expression of the duplicated/translocated genes.  They are usually lethal.

Non-Lethal Disruptions  Aneuploidy--Down Syndrome. It isn’t a duplication event, but essentially is like a duplication event.

Aneuploidy  Klienfelter Syndrome-XXY males. Have male sex organs but their testes are small and they are sterile.  Also have other feminine characteristics such as larger breasts.  They can be of normal intelligence, but most often exhibit some mental impairments.  Klienfelter Syndrome-XXY males. Have male sex organs but their testes are small and they are sterile.  Also have other feminine characteristics such as larger breasts.  They can be of normal intelligence, but most often exhibit some mental impairments.

Aneuploidy  XXX females cannot be distinguished from any other female except by karyotype.  XO are females with Turner’s syndrome. It is the only known monosomy in humans. They are sterile because their sex organs don’t mature, can develop 2° sex characteristics with hormone treatment.  XXX females cannot be distinguished from any other female except by karyotype.  XO are females with Turner’s syndrome. It is the only known monosomy in humans. They are sterile because their sex organs don’t mature, can develop 2° sex characteristics with hormone treatment.

Extranuclear Genes  These are the genes found on the chromosomes of organelles such as mitochondria and chloroplasts.  These are derived from the mother and replicate themselves.  They code for the proteins and RNA that they use to perform their particular functions.  These are the genes found on the chromosomes of organelles such as mitochondria and chloroplasts.  These are derived from the mother and replicate themselves.  They code for the proteins and RNA that they use to perform their particular functions.