Download AP Bio Ch 12

Chapter 12
The Chromosomal Basis of Inheritance
chromosome theory of inheritance
- Mendelian factors (genes) are located on chromosomes
- chromosomes segregate and independently assort
Thomas Hunt Morgan - provided evidence that Mendel’s inheritable factors are located on chromosomes
- studied the common fruit fly (Drosophila melanogaster) in early 1900s
Drosophila
- ideal organism to study:
reproduced quickly
produced many offspring
only 8 chromosomes(4 pairs):
3 pairs of autosomes
1 pair of sex chromosomes (females have 2 X-chromosomes and males have 1
X-chromosome and 1 Y-chromosome)
wild-type phenotype - phenotype for a character most common in nature
- example:
red eyes in Drosophila
mutant phenotypes
- traits alternative to wild type
- assumed to have originated as mutations in wild-type allele
- example:
white eyes in Drosophila
Morgan and colleagues
- invented symbols now used more widely than Mendel’s uppercase and lowercase letters
- for a character, the gene takes its symbol from the first mutant (non-wild type) discovered
- if the mutant is recessive, the first letter is lowercase (example: white eyes in
Drosophila are recessive  w)
- if the mutant is dominant, the first letter is capitalized (example: curly wings in
Drosophila are rare but dominant  Cy)
- a superscript “+” identifies the wild-type allele (example:  w+ for red eyes or Cy+ for normal,
straight wings)
After breeding Drosophila for a year, Morgan discovered a single male fly with white eyes instead of
wild-type red eyes. Morgan mated this mutant white-eyed male with a red-eyed female.
w = white-eyed allele
w+ = red-eyed (wild-type) allele
P generation: red-eyed female x white-eyed male 
w +w + x w
F1 generation: all F1 progeny had red eyes (suggested red was dominant to white)
Morgan then crossed an F1 female (red-eyed) with an F1 male (red-eyed)
F2 generation: - white eye trait appeared but only in males (all F2 females had red eyes)
Morgan’s conclusions:
eye color linked to sex
gene for eye color is on X-chromosome
- if eye color is located on X-chromosome, then females (XX) have 2 copies of the gene
while males (XY) have only 1
- since mutant allele (white eyes) is recessive, white-eyed females must have the alleles
on both X’s
- a white-eyed male has no wild-type allele to mask the recessive mutant allele, so a
single copy of the mutant allele is enough to confer red eyes
sex-linked genes
- genes on sex chromosomes
- commonly refers to genes on X-chromosome only
linked genes - located on same chromosome
- tend to be inherited together (do not assort independently)
- move together through meiosis and fertilization
- a dihybrid cross following 2 linked genes won’t produce an F2 phenotypic ratio of 9:3:3:1
Morgan performed a dihybrid testcross between flies with autosomal recessive mutant alleles for black
bodies (b) and vestigial wings (vg) and wild-type flies heterozygous for both traits:
bbvgvg
x
b+bvg+vg
black, vestigial wings
gray, normal wings
- progeny phenotypes were not in the expected 1:1:1:1 ratio
- many flies has same phenotype combinations as parents: gray with normal, black with vestigial
- Morgan concluded this was due to linkage  genes for body color and wing size are on same
chromosome and are inherited together
genetic recombination - production of offspring with new combinations of traits different from those
combinations found in the parents
- results from the events of meiosis and random fertilization
recombination of unlinked genes  independent assortment of chromosomes:
- Mendel discovered some offspring from dihybrid crosses have phenotypes unlike either parent
- pea plant testcross: YyRr x yyrr (genes for seed shape and seed color are unlinked)
- offspring: 50% parental types (YyRr, yyrr)
50% recombinant types (yyRr, Yyrr)
parental types - progeny with same phenotype as 1 of the parents
recombinants - progeny with phenotypes different from either parent
- when ½ progeny are recombinants, there is a 50% frequency of recombination
(indicates the 2 genes are on different chromosomes)
- genes for seed shape and color assort independently of each other because they are
located on different chromosomes
recombination of linked genes  crossing over
- if genes are linked, some phenotype combinations should never occur (but sometimes they do)
- example:
Morgan performed this dihybrid cross between fruit flies: b+bvg+vg x bbvgvg
b = black body
vg = vestigial wings
+
b = gray body
vg+ = wild-type wings
b+bvg+vg = gray, normal wings
bbvgvg = black, vestigial wings
2300 offspring:
Phenotypes
Genotypes
Expected results Expected results Actual results
for unlinked
if genes are
genes
totally linked
black, normal
bbvg+vg
575
0
206
+
+
gray, normal
b bvg vg
575
1150
965
black, vestigial bbvgvg
575
1150
944
+
gray, vestigial
b bvgvg
575
0
185
recombination frequency
=
# recombinants
x
100
# total offspring
recombination frequency
=
391/2300
x
100
- results show the 2 genes are neither unlinked or totally linked
=
17%
- if unlinked , they would assort independently
- 1:1:1:1 ratio of all possible phenotype combinations
- if linked, there would be a 1:1 phenotypic ratio of parental types only
- linkage is incomplete  most have parental phenotypes but 17% are recombinants
- this is due to crossing over during meiosis (prophase I)
- parts are exchanged between homologous chromosomes  new allele combinations
result
recombination frequencies
Sturtevant
- used to map a chromosome’s genetic loci
- some genes are linked more tightly than others
- recombination between b and vg is ~ 17%
- recombination between b and cn is ~ 9% (cn recessive allele for
cinnabar eyes)
- Morgan’s student
- said probability of crossing over between 2 genes is directly proportional to the distance
between them
- constructed chromosome maps using recombination frequencies
- 1% recombination frequency = 1 map unit (map units are now called centimorgans)
constructing a map:
loci
recombination frequency
b vg
17%
cn b
9%
cn vg
9.5%
1.
find distance between genes farthest apart
vg
b
2.
genes with highest recombination frequency are farthest apart
recombination frequency between cn and b is 9, so distance is about 9
cn
9
17
9
b
vg
b
cn
17
vg
17
consider possibilities:
or
3.
determine recombination frequency between other 2 genes to eliminate incorrect sequence
- “distance” between b and vg is 9.5 so second sequence is correct (b-cn-vg)
9
9.5
b
cn
vg
17
* distance between b and vg would be 18.5 but recombination frequency is only 17%
- their greater distance results in some double cross-overs which cancel each other out
linked genes so far apart that recombination frequency is 50%  indistinguishable from unlinked genes
Sturtevant
- mapped many genes this way
- found 4 major linkage groups
- correlated with the fact that Drosophila had 4 chromosomes (evidence that genes were on
chromosomes)
cytological mapping - locates genes with respect to chromosomal features (stained bands, etc.)
best gene maps
- constructed by sequences in DNA
- distances measured in nucleotides
sex chromosomes
- their presence or absence determine sex in most species
- each gamete contributes 1 sex chromosome at fertilization
heterogametic sex
homogametic sex
- produces 2 kinds of gametes
- determines sex of offspring
- produces 1 kind of gamete
some chromosomal systems of sex determination:
X-Y system (humans, mammals, fruit flies, etc.) male: XY
female : XX
X-0 system (grasshoppers, crickets, etc.)
male: X
female: XX
(sex determined by whether the sperm contains an X or no sex chromosome)
Z-W system (birds, some fishes, some insects)
male: ZZ
female: ZW
haploid-diploid system (bees, ants)
females: develop from fertilized eggs (diploid)
males: develop from unfertilized eggs (haploid)
chromosomal basis of sex in humans:
X-Y system  2 sex chromosomes (X and Y)
each gamete has 1 sex chromosome
2 possible combinations in gametes: XX (female) or XY (male)
males - heterogametic
- ½ sperm contain X; ½ sperm contain Y
females
- homogametic
- all ova contain X
presence of Y - determines maleness
- Y chromosome contains SRY gene (sex-determining region of Y) that triggers testicular
development (no Y  gonads become ovaries)
X-chromosome
- larger than Y-chromosome
- there are more X-linked traits than Y-linked (more genes on X)
- most X-linked genes have no homologous loci on the Y
Y-chromosome
- most genes code for traits found only in males
sex-linked traits in humans
- usually refers to X-linked traits
- examples: color blindness
Duchenne muscular dystrophy
hemophilia
Fathers pass X-linked alleles to daughters only (they give Y’s to their sons)
- males receive X-chromosomes from mothers
- fathers can’t pass sex-linked traits to sons
Mothers pass sex-linked alleles to both sons and daughters
- mothers pass 1 X to every son and daughter
recessive sex-linked trait
- more common in males than females
- females must be homozygous to express the trait
- heterozygous females are said to be carriers  XX’ (don’t show trait)
- if carrier mates with normal male, ½ her daughters will be carriers and half
her sons will express the trait
 XX’ x XY 
possible daughters: XX’ and XX
possible sons:
X’Y and XY
- if carrier mates with a male with the trait, ½ her children will have trait
 XX’ x X’Y 
possible daughters: X’X’ and XX’
possible sons:
X’Y and XY
hemizygous
- condition in which only 1 copy of a gene is present in a diploid organism
- example: a male human (only 1 X)
Lyon hypothesis
Barr body
- proposed by British geneticist Mary Lyon
- says 1 X is deactivated in female embryonic cells
- inactive X condenses into a Barr body
- inactivated X chromosome
- found along inside of nuclear envelope
- most genes not expressed
- reactivated in gonadal cells that undergo meiosis to form gametes
female mammals are a mosaic of 2 cell types:
those with active maternal X’s and those with active paternal X’s (inactivation occurs randomly
in embryonic cells)
- if a female is heterozygous for a sex-linked trait, about half her cells will express 1 allele and
the other cells will express the alternate allele (example: coloration in calico cats)
nondisjunction - failure of homologous chromosomes or sister chromatids to separate during meiosis or
mitosis
meiotic nondisjunction
- results in 1 gamete receiving 2 of the same chromosome and 1 gamete
receiving none
- may occur during meiosis I (homologous pair does not separate)
- may occur during meiosis II (sister chromatids do not separate)
mitotic nondisjunction
- also results in abnormal number of certain chromosomes
- if it occurs in embryonic cells, abnormal chromosome number is passed
onto many cells and can have a big effect
aneuploidy
- having an abnormal number of chromosomes
- aneuploid offspring may result when a normal gamete unites with an abnormal gamete
(due to nondisjunction)
- often results in spontaneous abortion of embryo
trisomy
- condition of having aneuploid cells with 3 copies of a certain chromosome
- example:
Down Syndrome (Trisomy 21)
monosomy
- condition of having aneuploid cells with a missing chromosome
polyploidy
- chromosome number that is more than 2 complete sets of chromosomes
- common in plants (rare in animals)
- example:
triploidy
- 3 haploid chromosome sets (3N)
- may be due to nondisjunction of all chromosomes during
egg formation
tetraploidy
- 4 haploid chromosome sets (4N)
- may result if a diploid zygote undergoes mitosis without
cytokinesis (followed by normal mitosis)
alterations in chromosome structure:
deletion
- removes a segment of a chromosome
- due to a nonreciprocal crossover  1 chromosome gives up more genes than it receives
duplication
- repeats a segment in a chromosome
- also due to a nonreciprocal crossover
- often have deleterious effects
inversion
- reverses a segment in a chromosome
reciprocal translocation
- segment moved from 1 chromosome to a nonhomologous chromosome
- often have deleterious effects
human disorders
Down syndrome
- result of trisomy 21 (aneuploid condition)
- affects 1 in 700 children in U.S.
- includes:
characteristic facial features
short stature
heart defects
mental retardation
susceptibility to respiratory infections
proneness to developing leukemia and Alzheimer’s disease
- most are sexually undeveloped/ sterile
- more common with older mothers
sex chromosome aneuploidies (remember: 1 Y will result in maleness; absence of Y results in femaleness)
- examples: Klinefelter syndrome - usually XXY
- phenotype: male
small testes
sterile
feminine body contour
normal intelligence
Extra Y
- XYY
- phenotype: normal male
tall
normal intelligence
normal fertility
Triple-X syndrome - XXX
- phenotype: usually normal female
normal fertility
Turner’s syndrome - X0
- phenotype: female
short stature
failure of secondary sex characteristic to develop
at puberty
sterile (internal sex organs do not develop)
expression of some traits may depend on whether they were inherited from mother or father:
Prader-Willi syndrome
- mental retardation, obesity, short stature, small hands and feet
- caused by a deletion of chr 15 which was inherited from father
Angelman syndrome
- uncontrollable spontaneous laughter, jerky movements, motor and
mental symptoms
- caused by a deletion of chr 15 which was inherited from mother
genomic imprinting
- induces intrinsic changes in chromosomes inherited from males and females
- causes certain genes to be differently expressed in offspring
- example:
Prader-Willi/ Angelman syndromes
Fragile X syndrome
- X-chromosome is abnormal (tip hangs on rest of chromosome by a thin thread)
- results in mental retardation
- more likely if abnormal X comes from mother rather than father
- may be due to maternal genomic imprinting
extranuclear genes
- found in organelles like mitochondria and plastids
- not inherited in Mendelian fashion (no meiosis)
- all come from mother
- in animals: zygotes receive mitochondria from ovum, not sperm
- in plants:
zygotes receive plastids from ovum, not sperm