IMPORTANT TIMELINE IN GENETICS & CYTOLOGY
1860’s: Mendel proposes inherited factors segregate & assort independently
1875-90: Cytologists work out processes of mitosis, meiosis
1900: Mendel’s principles of Segregation & Independent Assortment rediscovered
1902: Chromosomal Theory of Inheritance developed, links Mendelian genetics with chromosomal movements during meiosis
1910: Morgan discovers evidence that genes are located on chromosomes
Chromosome Theory of Inheritance
Tenets of Theory:
1. Mendelian factors (genes) are located on chromosomes
2. Genes segregate when homologous chromosomes separate during meiosis
3. Genes independently assort due to behavior of chromosomes during meiosis
Thomas Hunt Morgan traced gene to a specific chromosome during work
on genetics of fruit flies (Drosophila melanogastor)
Morgan traced a gene to a specific chromosome in flies … why fruit flies ?
Fruit fly (Drosophila melanogaster) characteristics:
- easily cultured in lab, prolific breeders
- have short generation time
- have only 4 pairs of chromosomes which are readily
visible with a microscope
These characteristics allowed for cycling through many experiments rapidly
Autosomes & sex chromosomes
Fruit flies have 4 pairs of chromosomes made up of: 3 pairs autosomes, 1 pair sex-determining chromosomes
Autosomes - any of the paired chromosomes other than sex-determining X & Y chromosomes
In flies X & Y allele combinations determine sex:
2 XX sex chromosomes = females
XY sex chromosomes = males
Morgan bred millions of flies in his “Fly Room” looking for those with new character traits or “mutants”
Morgan’s experiments followed mutant traits in genetic crosses
Morgan’s approach similar to Mendel’s, except Morgan tracked mutant phenotypic traits in crosses
Mutant phenotypes = phenotypes that are alternatives to the “wild type”
& due to mutations in wild-type gene
- wild types are normal & most common trait in popl’n
Types of Mutant Flies
Morgan's conventions on notation
1. Genes symbol based on 1st mutant observed (non wild-type)
2. If mutant recessive, 1st letter lowercase (w = white eye)
3. If mutant dominant, 1st letter uppercase: Cy = curled wings
4. Wild-type designated by superscript + over symbol for trait:
w+ = flies with normal red eyes
vg+ = normal sized wings not vestigial in
shape
Cy+ = allele for normal or straight wings
not curled
Fig. 14.2. Morgan's 1st mutant in fruit flies
Red-eyed
& white-eyed flies
Morgan's monohybrid cross; eye color in fruit flies
P: Red-eye females (XX) X white-eyed male (XY)
F1 Ratio: All flies had red-eyes with approximate
equal numbers of females & males (50:50)
F2 Ratio: 3 red-eyes: 1 white-eye
Well, this seems normal enough but there was an important twist: all
white-eyed flies were males
all red-eyed
flies were females
Morgan's sex-linked gene deduction
1. Gene for eye color located on X chromosome, no corresponding allele for eye color on Y chromosome
2. If eye color is located only on X chromosome, then females (XX) have 2 copies of gene while males have only 1 (XY)
3. Mutant allele recessive, white-eyed female must have allele on both X chromosomes (impossible for F2 females)
4. White-eyed male has no wild-type allele to mask recessive mutant, single copy of mutant allele confers white eyes
… let’s look at this using Punnet squares to be sure!
Wild type female (Xw+ Xw+) X mutant males
(Xw Y)
Red-eye female (Xw+ Xw) X red-eye males (Xw Y)
Discovery of a sex-linked gene:
Cross of white-eyed male X red-eyed female
P generation w+
w+ X
w
red-eyed female
white-eye male
F1 generation w+w
X
w +
red-eyed female red-eye
male
F2 generation: 1/4 w+w+ red-eyed female
1/4 w w + red-eyed female
1/4 w+ red-eyed male
1/4 w white-eye male
3:1 phenotypic ratio but white-eyed trait only in males
Sex-linkage & linked genes
Sex-linked genes = genes located on sex chromosomes (usually
applied to genes on the X
chromosome)
Linked genes = genes that are located on the same chromosome
and that tend to be inherited
together
Morgan's dihybrid testcrosses revealed linked genes and more...
Morgan’s dihybrid testcross experiments revealed linked autosomal genes
Hypotheses:
1. If genes are on different chromosomes they should assort independently
during meiosis
2. If genes are on same chromosome they should assort together during meiosis
Morgan’s Dihybrid Testcross experiment:
Crossed flies heterozygous for body color (gray or black) and wing
shape (normal or vestigial) with flies that were homozygous recessive (black
with vestigial wings)
Dihybrid testcross for flies varying in color &
wing shape
1. Dihybrid genotypes: b+b vg+vg X bbvgvg (double
recessive)
b+ = wild-type gray bodies
b = mutant black bodies
vg+ = wild-type normal wings
vg = mutant vestigial wings
2. Testcross to double recessives: bbvgvg = what phenotype?
3. If assort independently, in dihybrid testcross expect 1:1:1:1
phenotype ratios
FLY TESTCROSS DIAGRAM
Dihybrid testcross: results not 1:1:1:1
Morgan’s Dihybrid Testcross Summary
Phenotypes Resulting From Cross
Expected by:
Gray-normal Black-vestig Gray vestig
Black-normal
Independent
575
575
575
575
assortment
Linkage 1,150 1,150 0 0
Observed 965 944 206 185
1. Results definitely didn’t fit for Independent Assortment but were
close
to that expected due to linkage
2. Morgan’s conclusion: genes were linked, but linkage was incomplete
due to mechanism that occasionally
3. At the time it was not known that crossing over occurred & produced
genetic recombination,
eventually was shown that Morgan was correct
Genetic recombination results from independ. assortment & crossing over
Genetic recombination = production of offspring with new combinations
of traits apart from
those found in parents
Parental types = progeny having same phenotypes of one or other parent
Recombinants = progeny whose phenotypes differ from either parent
How genetic recombination occurs differs for unlinked & linked genes
1. Recombination of unlinked genes occurs by independent assortment
of chromosomes
Ex. Mendel’s dihybrid testcross:
YyRr (yellow-round) X yyrr (green-wrinkled)
Progeny: yellow-round (50%), green-wrinkled (50%)= parental type
green-round (50%), yellow-wrinkled (50%)= recombinants
2. Recombination of linked genes occurs by “crossing over” during meiosis
Ex. Recombinant phenotypes in Morgan’s flies ...
Dihybrid testcross with Drosophila varying in
body color & wing shape
Body color: Gray (b+), Black (b)
Wing shape: Normal (vg+), Vestigial (vg)
Figure: Dihybrid testcross with flies
Figure 14.5a & b: Recombination due to crossing
over
Recombination frequencies can be calculated from phenotypes of offspring
Points on Recombination for Linked genes:
1. Linkage seldom complete; genes that are close together are
more tightly linked than those
far apart…why??
2. Linked genes that are far apart may assort independently
Ex: Genes for seed color & flower color
in peas are now known to
be on same chromosome. They are so far
apart, however, Mendel
observed independent assortment…
Recombination data can be used to map genetic loci
Recombination frequencies vary for genes on the same chromosome: some genes more tightly linked than others
Sturtevant suggested that if crossing over were random, the probability
of crossing over is proportional to distance between genes
- gene pairs with higher recombination frequencies
are farther
apart than those with lower recombination
frequencies
A linkage map gives information on the relative positions of genes on
chromosomes
- one map unit is equal to 1% recombination frequency
Recombination frequencies for 3 genes on Chromosome II in flies
Body color (b) & wing type (vg) = 17%
Body color (b) & eye color (cn) = 9%
Eye color (cn) & wing type (vg) = 9.5%
Chromosomal basis of sex
Heterogametic sex = sex that produces 2 kinds of gametes and
determines the sex of the
offspring
Homogametic sex = sex that produces one kind of gamete
Hemizygous = condition where only 1 copy of gene present in
diploid organism
Figure: Human chromosomes: 22 homologous pairs, 1 pair sex chromosomes
Figures 14.8a-d: Some chromosomal systems of sex determination
Sex-linked disorders in humans
1. Fathers pass X-linked alleles to daughters only
2. Females pass X-linked alleles to sons & daughters
3. Sex-linked disorders much more common in males
- males are hemizygous, so if get mutant allele
from mothers
it is expressed
- females only have diseases if homozygous (usually
recessive)
Figure 14.9: The transmission of sex-linked
recessive traits
Genetic disorders can arise from altered chromosome
numbers or structure
Meiotic errors and mutagens can alter the structure or
numbers of chromosomes
Meiotic errors include:
1. Nondisjunction of homologous chromosomes or sister chromatids
2. Breakage & Crossing over errors: Deletions, duplications, inversions, translocations
Nondisjunction errors during Meiosis i
Nondisjunction errors during Meiosis II
Unusual chromosome number conditions: aneuploidy &
polyploidy
Polyploidy = chromosome number that is more than 2 complete chromosome
sets (3n, 4n, etc)
- Polyploidy condition rare in animals but relatively common
in plants
Aneuploidy = condition of having an abnormal number of certain chromosomes
in somatic cells (trisomy, monosomy)
Aneuploid condition causes characteristic symptoms or “syndromes” in
human survivors
Example = Down’s syndrome
Alteration of chromosome structure can result from:
1. Physical breakage
2. Crossing-over errors
Figure 14.12: Alterations of chromosomes
Other aneuploidy problems
Trisomy 13 - Patau syndrome
Trisomy 18 - Edwards syndrome
Sex chromosome aneuploidies are less severe
- Y chromosomes have few genes
- X-inactivation occurs in female mammals (Barr bodies Fig. 15.10)
X-Inactivation in Female Mammals
Female calico cats: X chromosome inactivation influences coat
color
- allele on one X chromosome for black, other X has allele for orange
- patchwork of orange, black pelage results from inactivation of one
or other of these X chromosomes during early development
Extranuclear genes & non-Mendelian inheritance
in eukaryotes
Extranuclear circular genes are found in cytoplasmic organelles
(chloroplasts, mitochondria)
Cytoplasmic genes of these organelles are not inherited in Mendelian fashion as are genes on nuclear chromosomes
Genes on chloroplasts & mitochondria maternally inherited with cytoplasm
1. In most eukaryotes eggs contain large amounts of cytoplasm but sperm
or pollen does not
2. Mitochondria & chloroplasts in zygotes come only from female
egg so DNA of these is inherited with cytoplasm