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Classical Papers in Genetics
Olga Russakovsky
10 / 28 / 04
CS 374
Outline
Sulton, W. S. The Chromosomes in Heredity, 1903
Demerec, M. What is a Gene? 1933
Crick, Francis. Central Dogma of Molecular Biology, 1970.
1903
The Chromosomes in Heredity
Background: Mendel’s experiments
Cell organization and division
Which chromosomes?
Roles of chromosomes
Alleles and dominance
Mendel’s experiments
Peas 1:2:1 genotypic ratios, 3:1 phenotypic
Mendel’s brilliant conclusion: “while in the organism maternal and paternal
potentialities are present in the field of each character, the germ cells in respect to each character are pure.”
Deviations from Mendel correspond to deviations in chromosome processes
Cell organization and division Bateson quote
“It is impossible to be presented with the fact that in Mendelian cases the crossbred produces on an average equal numbers of gametes of each kind, that is to say, a symmetrical result, without suspecting that this fact must correspond with some symmetrical figure of distribution of the gametes in the cell division by which they are produced.”
Cell organization and division Relationships between chromosomes and
genes in Brachystola1) Prophase – two equivalent chromosome series
(maternal and paternal)
B
CB
C
A
A
Cell organization and division Chromosomes and genes
2) Metaphase (synapsis) – union of pairs of the homologues
B CB CAA
Cell organization and division Chromosomes and genes
3) Meiosis II – first postsynaptic division equational, so no differentiation
B CB CAA
B CB CAA
Cell organization and division Chromosomes and genes
4) Meiosis I (reducing division) – separation of homologous chromosomes
BC
BC
AA
B CB
C
AA
Cell organization and division Chromosomes and genes
5) Chromosomes retain individuality throughout cell cycle
BC
BC
AA
B CB
C
AA
Which chromosomes? Do all maternal chromosomes go to one
pole, and paternal to the other? Probably not
BC
BC
AA
B CB
C
AA
versus
Which chromosomes? If maternal and paternal separated,
1) No crossbreeding can produce more variety than first cross
Consider AB x AB ABAB parent cell ½ AB and ½ AB germ cells
Then crossbreeding yields germ cells:AB
AB
AB
AB
AB
½ AB½ AB
½ AB½ AB
AB
½ ABand ½ AB
Which chromosomes? If maternal and paternal separated,
2) Only 4 different combinations in offsprings of a single pair
Consider AB x CD ¼ AC, ¼ AD ¼ BC, ¼ BD
A B C D
AB CD
AC, AD, BC, BD
Which chromosomes? If maternal and paternal separated,
3) Can receive traits from only one grandparent each from the paternal and maternal lines
A B C D
AB CD
AC, AD, BC, BD
Which chromosomes? More careful research
Matter of chance, paternal or maternal
ABCDABCD 16 different possible germ cells:
ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD, ABCD
Only 2 possible combinations
X
2 unrelated individuals:256 possible offsprings!
Which chromosomes? So for humans, with
16 chromosomes minimum:
8 homologous pairs, so 28, or 256, combinations
of germ cells, so (28)2, or some huge
number, of possible children
Which chromosomes? This “serves to bring the chromosome theory into
final relation with the known fact of heredity; for Mendel himself followed out the actual combinations of two and three distinctive characters and found them to be inherited independently of one another and to present a great variety of combinations in the second generation.”
Roles of chromosomes Numbers can’t confirm roles
Studies of larvae lacking certain chromosomes
Confirmed relationship between characters and chromosomes
Studies of Brachystola confirmed law of segregation of characters
Roles of chromosomes Similarities between germ-cell division and
heredity: Purity of units
Independent transmission So half of offsprings contain each trait
Evidence and experiments double basis for each character, even in pure-
breeding forms, because of pairs of homologues
Alleles and Dominance Definite relationship between allelomorphs,
or unit characters, and chromosomes
Entire chromosome or only part is an allele?
Think about variety!
At least some must carry multiple alleles (i.e. multiple genes)
Alleles and Dominance Chromosome entirely dominant, or divided
into parts?
Greatly increases variety, yet also greatly increases complexity of research
Breakthrough: sometimes observed correlation between traits
Explanation: same chromosome, sometimes both traits dominant over homologue, sometimes only one dominant
Alleles and Dominance
Chromosome 1: ABChromosome 2: ab
Offsprings: observed correlation between traits
Chromosome 1: AbChromosome 2: aB
Offsprings: no observed correlation (opposite correlation, actually)
Key: A = green color of seeda = brown color of seedB = big leavesb = small leaves
1933
What is a gene?
Gene definition analyzed
Stability of the gene
Nature of gene changes
Role of genes
Gene definition Gene:
a minute organic particle
capable of reproduction
located in a chromosome
responsible for the transmission of a hereditary characteristic
Goal: to see how this definition can be extended
Gene definition Size of gene
Determine volume of chromosomes, approximate number of genes, and divide one by the other
Proposed upper limits: 10, 20, 50, 60, 70 millimicrons
About a few organic molecules
genes
Gene definition Size of gene
Ultramicroscopic particle?
Some direct evidence
Chromosomes not visible inside nucleus until division
Work with x-rays
Change in the gene as a result of being hit by photoelectron
Effects size of a single organic molecule
Gene definition Capacity of reproduction
Little is known about gene reproduction
Evidence from study of unstable genes: formation of new gene next to old one rather than division of old one
Single molecule
Transmission of hereditary characteristics
Overall effect determined by all genes
Gene definition
Location of genes Linear order
Permanent locus Order changes
=abnormalities
Genetic distances ≠ actual distances
Height
Hair color
Finger length
Nail shape
Eye color
Stability of the Gene Mutations
Change from one allele to another
Occur naturally, at very low rate
X-rays and radiation increase that rate
Different frequency in different genes
“Unstable” genes
Continuous series
Rates differ in different tissues, and different stages of development.
Stability of the Gene
Stability of the Gene Experiment
Two unstable genes for color, lavender and rose
Both change to purple
Number of purple spots number of changes
Size of the spots stage of ontogeny when change occurred
Lavender flowers, small spots lavender gene unstable late in development
Rose flowers, varying spots unstable in all stages
Stability of the Gene Somatic vs. germ cell mutations
Easier to observe large numbers of somatic cells
Of two genes changing at the same rate, one which change in germ cells only will be “more stable”
So “unstable” vs. “stable”
higher frequency and
change in tissues where easily detected
Role of genes Conclusion of studies:
Any radical change eliminates the gene from the gene complex, and the elimination of a single gene usually is lethal
Therefore… The primary function of gene is not the one by
which we recognize it (determination of phenotypes), but the regulation of life processes of the cell!
1970
Summary