LON-CAPA Lecture 25: Linked Genes, Sex Determination and Linkage, and Organelle Inheritance<br> DNA and Its Role in Heredity

Lecture 25: Linked Genes, Sex Determination and Linkage, and Organelle Inheritance

Genes and Chromosomes
1. If genes are on chromosomes, then there must be several genes on any one chromosome since there aren't enough chromosomes to account for all of the genes.
2. The consequence of having more than one gene on a chromosome is that the genes may be transmitted together more often than expected. This is a violation of Mendel's Second Law.
3. Remember that non-sister chromatids of non-homologous chromosomes exchange parts (crossing over) during prophase of meiosis I.
4. If two, linked genes are located on either side of such a crossover, it is possible to see assortment of the alleles.
5. The frequency of crossovers between two genes is measurable and relatively consistent when the mating is done repeatedly.
6. This has been used to"map" genes on chromosomes although the recombination derived map has no physical units.
7. The recombination derived map is co-linear with a physical map.
8. The actual sequencing of chromosomes has reduced the utility of such genetic maps to some degree.

Sex Determination and Chromosomes
1. In most animals, the chromosomes associated with sex determination are dimorphic - one chromosome is much larger than the other or, at least, there are two distinctive chromosomes.
  - Mammals and Drosophila have an XX/XY system although the basic mechanism of sex determination differs.
    Basically, females are XX (homomorphic) and males are XY (heteromorphic) and the Y chromosome is much smaller than the X.
  - Birds have a ZW/ZZ system where females are ZW (heteromorphic) and males are ZZ (homomorphic).
  - Some animals (grasshoppers) have an XX/XO system where females are XX and males have only one X chromosome and no other chromosome. Curiously, XO fruit flies are male but XO humans are females.
  - Honeybees have a diploid/haploid sex determination mechanism where fertilized eggs develop into females and unfertilized eggs develop into males. This make the drone males nothing more than flying gametes.
2. The chromosomes not associated with basic sex determination are known as autosomes.
3. The X and Y chromosomes share some gene homology but have other quite different genetic content.
  - At least one gene on the Y chromosome in mammals is directly associated with inducing the male pattern of embryonic development. This sets into motion which type of gonad the embryo will contain and the hormones produced by that gonad will influence the secondary sexual characters.
  - Other genes on the Y-chromosome are associated with sperm maturation.
  - Most of the genes on the X chromosome in humans are not represented on the Y chromosome. This means that human males are hemizygous for X-linked genes. It also means that X-linked inheritance patterns are different from autosomal inheritance patterns.

Sex Linked Inheritance
1. X-linked recessive
  - Grandfather to grandson transmission through unaffected daughter/mother.
  - More affected males than females.
  - Affected females must have had an affected father and will have all affected sons.
  - Half of the sons of carrier (heterozygous) females will be affected.
  - Examples: hemophilia, color-blindness, steroid sulfatase, G6PD, Lesch-Nyhan, Duchenne Muscular Dystrophy, and many others.
2. X-linked dominant
  - Affected females transmit to half of progeny independent of sex.
  - Affected males transmit to all daughters.
  - More affected females than males.
  - Examples: vitamin-D resistant rickets.
3. Y linkage
  This shows a strictly male to male transmission pattern and can be used to trace male lineages.

Cytoplasmic Inheritance
1. Mitochondria and chloroplasts contain DNA which codes for organelle specific proteins.
2. These DNA molecules can be mutated and those alleles are transmitted to the progeny.
3. In general, the transmission of these traits is through the cytoplasm of the egg and not through the sperm or male gamete.

Lecture 25: DNA and Its Role in Heredity

Early Experiments Demonstrate that DNA is the hereditary material
1. Bacteria can be"transformed"
  - Griffith and in vivo bacterial transformation
    - two strains of Streptococcus pneumoniae:
      Smooth (enclosed in a polysaccharide capsule) = virulent
      Rough (lacking the polysaccharide capsule) = nonvirulent
    - inject mice with heat killed Smooth bacteria and mice survive
    - inject mice with heat killed Smooth bacteria and live Rough bacteria and mice die and can recover live Smooth bacteria from dead mice
    - conclude that something in the heat killed Smooth"transformed" the Rough in a stable manner
  - Hotchkiss and others demonstrated that this bacterial transformation could be carried out in vitro
2. The"transforming principle" is DNA
  - in 1944, Avery, Macleod, and McCarty treated"transforming principle" with different degradative enzymes
  - treatment with enzymes that degrade polysaccharides did not destroy"TP"
  - treatment with enzymes that degrade proteins did not destroy"TP"
  - treatment with enzymes that degrade RNA did not destroy"TP"
  - treatment with enzymes that degrade DNA DID destroy"TP"
  - the transforming principle is sensitive to DNase so it must be DNA
3. Hereditary material of bacterial viruses is DNA
  - in 1952, Hershey and Chase grew bacteriophage T2 which consists of only a protein coat enclosing a DNA core in the presence of either
    radioactive phosphorus (³²P) to label DNA, or
    radioactive sulfur (³⁵S) to label proteins
  - allowed labeled phage to absorb to bacteria and then put the infected bacterial cells in a Waring blender
  - bacteria infected with DNA labled phage retained the label
  - bacteria infected with protein labeled phage lost the label
  - the progeny phage contained labeled DNA but not labeled protein
  - Sinsheimer and in vitro replication of DNA to yield infectious DNA

The structure of DNA meets the requirements for the hereditary material
1. DNA structure
  1. Basic chemical units
    1. a 5 carbon sugar - deoxyribose
    2. phosphate - link between sugars
    3. bases: purines = adenine and guanine
      pyrimidines = thymine and cytosine
  2. One strand
    Each strand is made up of a sugar covalently linked to a phosphate which is covalently linked to another sugar and so on. A DNA strand may contain thousands to millions of these sugar-phosphate units.
    Each sugar also has a purine or pyrimidine base attached to it through a covalent bond.
  3. Double helix
    A DNA molecule consists of two strands which are coiled around each other in a double helix. The bases in the opposite strands are arranged such that where there is an adenine in one strand, the other strand has a thymine and where there is a guanine in one strand, the other strand has a cytosine. This satisfies Chargoff's rule such that:
    the amount of adenine = the amount of thymine (A = T)
    the amount of guanine = the amount of cytosine (G = C)
  4. Directionality
    The linkage of the sugar-phosphate"backbone" of a single DNA strand is such that there is a directionality. That is, the phosphate on the 5' carbon of deoxyribose is linked to the 3' carbon of the next deoxyribose. This lends a directionality to a DNA strand which is said to have a 5' to 3' direction. The two strands of a DNA double helix are arranged in opposite directions and are said to be anti-parallel in that one strand is 5' - 3' and the complementary strand is 3' - 5'.
2. Requirements for hereditary material
  1. Information
    The hereditary material contains biologically useful information and specifies the linear sequence of amino acids in a polypeptide chain (protein).
  2. Reproduction
    The material must be replicated faithfully and transmitted to progeny cells and to succeeding generations.
  3. Stability
    The material must be stable within the confines of a living organism.
  4. Mutability
    The material must be capable of incorporating stable changes (mutations) which become transmissible to succeeding generations.
3. DNA meets the requirements
  1. Information
    DNA is made up of two, complementary chains of nucleotide bases (A, G, C, and T). The linear sequence of these bases provides information content via a genetic code in which three, consecutive bases specifies one amino acid.
  2. Reproduction
    The complementarity of base pairing between the two strands (A always pairs with T and G always pairs with C) means that each DNA strand contains the template information necessary for the synthesis of the complementary strand.
  3. Stability
    Each strand of DNA is held together by strong, covalent bonds. The complementary strands are held together by hydrogen bonds. Although hydrogen bonds are"weak" bonds, the summation of a large number of these"weak" bonds results in a stable molecule.
  4. Mutability
    Changes in the sequence of bases can occur through a number of known mechanisms.

This document maintained by Robert J. Huskey.
Last update on October 29, 1999.