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