Brief History of Genetics• prehistory,

– “artificial selection” non-random breeding with no guarantee of results,

• human mediated natural selection

• Canis lupis (wolf) to Canis domesticus (dog),

– helpful, friendly companions lived to breed,

– savage, misbehaving wolves = stewpot,

– oldest undisputed dog bones, 20,000 years at an Alaskan settlement.

Gourds!Lagenaria vulgaris

Why I Am a Biologist?

‘Prehistory’ of Genetics

• By around 10,000 years ago, the same approach yielded,

– reindeer, sheep, goats, pigs, cattle, fowl, etc.

– rice, barley, wheat, lentils, corn, squash, tomatoes, potatoes, peppers, yams, peanuts, gourds, etc.

– yeast and bacteria for fermentation, etc.

Northwest Palace of Ashurnasirpal II (833-859 B.C.)

• Selective breeding: purposeful control of mating by choosing parents for the next generation.

• 1929 survey of 3 oases in Egypt identified 400 varieties of dates.

• DNA evidence now allows us to unravel prehistorical genetic manipulations.

History of Modern Genetics

• By the 19th century, precise techniques for selective breeding allowed the systematic creation of strains in which offspring often had prized traits.

– However, the traits would unpredictably disappear in some generations and return in others.

Moravian Sheep Breeders Association (1837)One breeder’s dilemma…

I have an outstanding ram that would be priceless “if its advantages are inherited by its offspring…if they are not inherited, then it would be worth no more than its wool, meat and skin.”

Abbot Cyril Napp

• In concluding remarks to the Moravian Sheep Breeders Society, Abbot Cyril Napp proposed that breeders could improve predictions of traits in offspring if they determined the answers to three basic questions;

– What is inherited?

– How is it inherited?

– What is the role of chance in heredity?

Monastery of St. ThomasBrno, 1843

• Abbot Cyril Napp, master of the monastary admitted Johann Mendel, a gifted student from a poor peasant family,

– Johann changed his name to Gregor,

– was sent to the University of Vienna,

• studied physics, chemistry, botany, paleontology and plant physiology,

• resolved to answer Abbot Napps three questions.

Prevailing Genetic ‘Philosophies’

• Philosophy 1: one parent contributes most to the offspring,

– the homunculus did it,

• Aristotle contended that it was the male, via a fully formed being in the sperm,

• Respected 19th microscopists staked their reputation that they could see the homunculus in sperm.

Prevailing Genetic ‘Philosophies’

Philosophy 2: blended inheritance,

– parental traits are mixed and become forever changed in the offspring.

To begin a Science of Genetics

• careful observation, over time, of large numbers of organisms,

– identify significant variables,

– measure the variables meticulously,

• rigorous (i.e. mathmetical) analysis of these observations,

• development of a theoretical framework to explain these

observations.

Napp’s Questions

• Napp…

– “What is inherited?”

– “How is it inherited?”

– “What is the role of chance in heredity?”

Mendel Insight 1

• Use the pea,

Insight 2

• alternate forms,

Insight 3

• True breeding lines,

– “Permit me to state that, as an empirical worker, I must define constancy of type as the retention of character during the period of observation”. -Mendel

– Mendel observed his ‘true-breeding’ lines for up to 8 generations.

• Used the pure-breeding line to form hybrid lines,

– offspring of genetically dissimilar parents.

Insight 4

• Expert plant breeder,

– carefully controlled the matings,

• prevented the intrusion of any pollen foreign to the desired mating,

– made reciprocal crosses:

• reversing the traits of the male and female parents,

– male wrinked x female smooth,

– female wrinkled x male smooth.

Insight 5

• Used large numbers of subjects,

– applied statistical analysis to his data!

• uncovered the patterns of transmission that we

“eventually” will take for granted.

Insight 6

• Controlled for environmental factors,

– for example, when looking at the short and tall

plants, he made sure that all subjects received

equal light,

• from his studies of plant physiology, he knew that

light mediates stem elongation.

Insight Summation

• Used the pea,• Identified alternate forms,• Identified and used true breeding lines,• Expert plant breeder,• Used statistical analysis,• Controlled for environmental factors.

Set up a simple ‘black and white’ system, and then figured out how it worked.

Monohybrid Cross Mating between individuals that

differ in only one trait.

Monohybrid Cross

Generation

Parental (P)

First Filial (F1)

Second Filial (F2)

yellow pea green pea (pollen) (eggs)

x

all yellow

grow plants, cross pollinate

grow, allow to self-fertilize

6022 yellow : 2001 green

3 : 1

Reappearance of Trait in F2 Generation Disproves Blending

• Blending did not occur, in fact over 2000 peas retained the information necessary to make green peas,

• Mendel concluded that there must be two types of yellow peas,

– those that breed true like the parent plant,

– those that can yield some green peas, like some of the F1 hybrids.

Reciprocal Crosses Disproved Influential Parent Myths

• In all monohybrid crosses, the ratio of contrasting traits was approximately 3:1,

– in the yellow(male) x green (female) pea cross, three yellow peas were produced for

every green pea in the F2 generation,

• Independent of which parent carried the dominant trait...

Dominant vs. Recessive Traits

x P

F1

The trait that appears in the F1 generation is the DOMINANT trait.

The trait that disappears in the F1 generation is termed RECESSIVE.

Nomenclature

• Dominant unit factors are designated with a capital letter, often (but not always) with the first letter of the description,

– Y = yellow,– V = violet,

– T = tall,

• Recessive unit factors are represented by small letters,

– y = green,– v = white,– t = dwarf,

Nomenclature II…it’s not my fault.

• Dominant unit factors are designated with a capital letter,

– G = yellow,– W = violet,

– D = tall,

• Recessive unit factors are represented by small letters, often (but not always) with the first letter of the description,

– g = green,– w = white,– d = dwarf,

Mendel’s First Postulate

Unit Factors in Pairs• Genetic characteristics are controlled by unit

factors that exist in pairs in individual organisms,

– each individual receives one unit factor from each parent,

– in a monohybrid cross, three combinations of unit factors are possible,

Definitions to Know

• Homozygous: the unit factors that determine a particular trait are the same,– YY = homozygous dominant,– yy = homozygous recessive,

• Heterozygous: the unit factors that determine a particular trait are different,– Yy = heterozygous.

Mendel’s Second Postulate

Dominance/Recessiveness

• When two unlike unit factors are present in a single individual, one unit factor is dominant to the other, which is said to be recessive.

Unlike Unit Factors=

Alternate Forms of the Same Gene

=

Alleles

Unit Factors = Genes• three combinations of alleles are possible,

YY

Yy

yy

Molecular Alleles

Fig. 2.4

Mendel’s Third Postulate

Segregation

• During the processes of heredity, the paired unit factors separate so that the offspring receives one unit factor from each parent,

• The unit factors segregate to offspring randomly.

When Unit Factors Separate

Two Unit Factors = Diploid

One Unit Factor = Haploid

During Gamete formation, Unit Factors Separate

More Definitions to Know

• Phenotype: an observable trait,

• Genotype: the actual alleles present in an individual.

Mendel’s First Three Postulates

Unit Factors in Pairs

Dominance/Recessiveness

Random Segregation

Postulates 1-3 AppliedP1 - F1 Generation

P1: Yellow Green Phenotype YY yy Genotype

Gametes: Y y

Yellow PhenotypeF1: Yy Genotype

Postulates 1-3 AppliedF1 - F2 Generation

Yellow F1: Yy

F1 Self-Cross: Yy Yy

Gametes: Y or y Y or y

F2:

Yy Yy yyYY

3 : 1 Phenotypic Ratio(1:2:1 Genotypes)

1 : 1 : 1 : 1

Yellow Yellow Yellow Green

F2: YY Yy Yy yy

homozygous heterozygous heterozygous homozygous

dominant recessive

Punnett Squares

Y y

Y

Y

YY

YY

Yy

Yy

gametes Parent 1

gametes Parent 2

Predicted Offspring In Squares

Back to the Moravians

• So, you’ve got a prize ram, how do you tell it’s not a dud dad?

S = stud

s = dud

SS or Ss?

Test Cross

• Your ram has a stud phenotype, but unknown genotype,

– cross it to a homozygous recessive individual,

s s

S

s

Ss Ss

ss ss

s s

S

S

Ss Ss

Ss Ss

all studs half studs, half duds

3 : 1 Phenotypic Ratio(1:2:1 Genotypes)

1 : 1 : 1 : 1

Yellow Yellow Yellow Green

F2: YY Yy Yy yy

homozygous heterozygous heterozygous homozygous

dominant recessive

Test Cross

• Your ram has a stud phenotype, but unknown genotype,

– cross it to a homozygous recessive individual,

SS x ss Ss x ss

all stud 1/2 stud, 1/2 dud

The phenotypic ratio is the same as the allele ratio in the tested parent!

Extra Credit(formatted for lecture)

• Unrelated couples have a 3-4% chance of having an offspring with a genetic based birth defect. Cousin-mating only raises the risk by 1.7 - 2.8% more. The report compiled the results of six studies on thousands of cousin-couplings.

• Although there is an increased risk, it is very small. Significantly, the additional risk is mitigated by standard genetic counseling.

• It is illegal in 30 states to marry your first cousin,

– for many cultures, familial marriages are the cultural norm,– legal issues, social stigma, family strife, and decisions such as abortions resulting from overestimates of risks may

need to be reconsidered.

Byline: Denise Grady, NYT Who: Dr. Arno MotulskyWhere: U. Washington

No Genetic Reason to Discourage Cousin Marriage, Study FindsApril 3, 2002

Chance and Probability

Chance 100% 50% %0

Probability 1 0.5 0

(1/2), fractions are often used in genetics.

Laws of Probability

• Product Law: the probability of two or more independent outcomes occurring is equal to the product of their individual probabilities.

…text uses the term (Multiplication Law).

Laws of ProbabilityProduct Law Example

• 1 Stud sheep offspring = .5• 2 Stud sheep offspring = .5 x .5 = .25• 3 Stud sheep offspring = .5 x .5 x .5 = .125• 8 Stud sheep offspring = .5 x .5 x .5 x .5 x .5 x .5 x .5 x .5 = .004

• 10 stud sheep offspring = .001 = 0.1%

– or, you have a 99.9% chance that your Ram is a Stud.

If S_ offspring, the probability IF that parent was Ss…

Mendel’s Forth Postulate

Independent Assortment

• How do two traits segregate in the offspring of an individual that is heterozygous for both traits?

Dihybrid Crosses

• Monohybrid Cross,– one set of contrasting traits,

• Y (yellow) versus y (green).• S (smooth) versus s (wrinkled).

• Dihybrid Cross,

– SSYY x ssyy

Dihybrid Cross,

Smooth/yellow wrinkled/green

SSYY x ssyy

SY sy

SsYy

phenotype

genotype

gametes

genotype

P

F1

Dihybrid Cross,

smooth/yellow

SsYy

SY sY Sy sy

phenotype

genotype

gametes

genotype

F1

F2?

Gamete Formation in F1 Dihybrids

S s Y y

SY Sy sY sy

genotype

gametes

probability.25 .25 .25 .25

Mendel’s Results(phenotypes)

• Y_ S_ = 315

• yyS_ = 108

• Y_ss = 101

• yyss = 32

= 9

= 3

= 3

= 1

• S_ Y_

• S_yy

• ss Y_

• ssyy

= 9

= 3

= 3

= 1

Independent Assortment

• Y_ = 12

• yy = 4

• S_ = 12

• ss = 4

Still 3:1 ratios!

Monohybrid Cross…and probability

P: GG x gg

F1: Gg

Gametes: G g G g1/2 1/2 1/2 1/2

F2:

GG

1/2 x 1/2

1/4

Gg

1/2 x 1/2

1/4

gG

1/2 x 1/2

1/4

gg

1/2 x 1/2

1/4

Laws of Probability

Sum Law: The probability of an outcome that can occur in more than one way is the sum of the probabilities of the individual events.

Random Segregation

F2: GG Gg gG gg

1/4 GG 1/4 Gg 1/4 gG 1/4 gg

1/4 GG 1/2 Gg 1/4 gg

Problem

You cross YYSs x YySs individuals.

What are the expected phenotypic ratios?

use a Punnett Square, and/or probability calculations to get your answer.

YYSs x YySs

YS YS YsYs

YS

Ys

ys

yS

YSYS

YSYS

YSYs

YSYs

YSYs

YSYs

YsYs

YsYs

YSyS

YSyS

YsyS

YsyS

YSys

YSys

Ysys

Ysys

• S_ Y_

• S_yy

• ss Y_

• ssyy

= 12

= 4

Using ProbabilityWWMD

YY x Yy Ss x Ss

YYSs x YySs

Independent Assortment

YY or Yy SS Ss ss

gametes

.5 .5 .5.25 .25 probability

(p) Y_ = 1 (p) S_ = .75 Product Rule: (p) Y_S_ = .75

(p) ss = .25 Product Rule: (p) Y_ss = .25

Random Segregation

Assignment

• Probability, know it well,

• Start mastering problems 2.1 - 2.19 (all),

• Central Dogma Quiz Wednesday