Biology 321
 The inheritance
patterns discovered by
Mendel are true for genes
that are located on
autosomes
 What is an autosome?
1
The fly room at Columbia University ~ 1920
l to r: Calvin Bridges, A. sturtevant, Thomas Hunt Morgan
Early 20th century fly guys
 What do the inheritance patterns of sex-linked traits look like?
 First look at experiments done in the early 1900’s by a fruitfly
geneticist named Thomas Hunt Morgan
2
 The fruit fly Drosophila melanogaster has been used
extensively in genetic research because it is a good experimental
organism:
• small size (2mm)
12 day generation time large broods of progeny
• external anatomy provides for all sorts of possibilities for interesting
phenotypic variation
The complete DNA sequence of the fly genome was
completed in 2000
3

Morgan was doing a routine transfer of his wildtype stocks when he noted a white-eyed male fly in
among a stock of wild-type red-eyed animals
What do we mean by wild-type phenotype?
4
Wild-type phenotype: the phenotype observed in the standard lab
stock or seen most commonly in the wild population
In Drosophila,
red eye color is
the wild-type
phenotype
5
Morgan retrieved this white-eyed fly and did a series of crosses:
Male fruitflies have
a stereotyped
courtship display
involving following
and wing-extension
and vibration: see
link below form or
info
http://fire.biol.wwu.edu/trent/trent/fruitflymating.jpg
6
It’s not just about white vs red eyes
or curled vs straight wings
There are many mutant strains of Drosophila where the male
courtship display is abnormal.
The fruitless mutation (next page) causes males to court other
males as well as females.
7
.
Genetics. 1989 April; 121(4): 773–785.
See also:
http://fire.biol.wwu.edu/trent/trent/NYTgayfruitflies.pdf
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Jargon check
Statement: Fruitless homozygotes court both male and
female fruitflies
What we really mean: Male fruitflies that are homozygous
for a loss-of-function mutation in the fruitless gene court both
male and female fruitflies. Wild-type males court females
only.
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Using models to explore the genetic control of behavior
Learning From the Spurned and Tipsy Fruit Fly
3/15/12 New York Times By BENEDICT CAREY
http://video.nytimes.com/video/2012/03/16/science/100000001430045/drunken-fruit-flies.html?scp=3&sq=fruit%20fly%20alcohol&st=cse
Fig. 1. Mating and chronic sexual
deprivation have opposite effects on
voluntary ethanol consumption.
They were young males on the make,
and they struck out not once, not twice,
but a dozen times with a group of
attractive females hovering nearby. So
they did what so many men do after
being repeatedly rejected: they got
drunk, using alcohol as a balm for
unfulfilled desire. And not one flew off
in search of a rotting banana. Fruit flies apparently self-medicate just like many humans
do, drowning their sorrows or frustrations for some of the same reasons, scientists reported
Thursday. Male flies subjected to what amounted to a long tease — in a glass tube, not a
dance club — preferred food spiked with alcohol far more than male flies that were able to
mate.
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• This study, in the journal Science*, suggests that some
elements of the brain’s reward system have changed very
little during evolution, and these include some of the
mechanisms that support addiction.
• Levels of a brain chemical that is active in regulating appetite
predicted the flies’ thirst for alcohol and a similar chemical is
linked to drinking in humans.
• “Reading this study is like looking back in time, to see the very
origins of the reward circuit that drives fundamental
behaviors like sex, eating and sleeping,” said Dr. Markus
Heilig, the clinical director of the National Institute on Alcohol
Abuse and Alcoholism and the National Institute on Drug
Abuse.
*Sexual Deprivation increases ethanol intake in Drosophila Science 335:1351 2012
Want to know more about genes and behavior? Check out this link:
http://www.nature.com/scitable/topicpage/Behavioral-Genomics-29093
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MEANWHILE back to MORGAN’S experiments
[we will work through the crosses on the board]
 These results differed from typical Mendelian results in two ways:
1. The results of reciprocal crosses were different
2. F2 progeny ratios not in quarters
 Remember that when Mendel performed reciprocal crosses between his various plant lines, he
always go the same result: when he crossed yellow with green he always got yellow F1 regardless
of whether the pollen came from the green-seeded plant or the yellow-seeded plant
 This will almost always be true if the gene for the trait is located on an autosome
 Morgan interpreted the results of these crosses using information that he had about the
chromosome constitution of Drosophila
 Morgan knew that Drosophila females had 4 regular chromosome pairs but that Drosophila
males had 3 regular chromosome pairs plus a heteromorphic pair
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What does heteromorphic mean?
prophase of meiosis I in the testis of a salamander
13
 Heteromorphic means literally different form: a heteromorphic
chromosome pair is a chromosome pair in which there is some
difference in size or shape between the two chromosomes that
synapse during prophase of the first meiotic division
14
 A Drosophila male has an X and a Y chromosome
 These X and Y chromosomes synapse and segregate during meiosis I
like autosomal homologues would.
 To explain his data, Morgan proposed that a gene for eye color in
Drosophila was present on the X chromosome with no counterpart on the
Y chromosome
 Thus females would have two copies of the gene and males would
have one copy
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 Assigning allele symbols
 Mendel’s style of allele notation would use the letter R (dominant
phenotype is red eyes) as the gene designation with
R= red (dominant) allele
r= white recessive allele
 Drosophila geneticists assign a name and letter symbol to the gene based on
the mutant phenotype.
• So the gene that differs in the white and red-eyed flies is designated the
white (w) gene
• In Drosophila, wild-type allele is often indicated as a “+ “superscripted.
• w+ = wildtype (red) allele
• w = mutant (white) allele
 Fill in the genotypes of the reciprocal crosses: use Xw+ for red, wild-type
allele and Xw for white allele.
 The results of the reciprocal crosses are consistent with the eye color gene
being on the X chromosome with no counterpart on the Y chromosome
16
Conventions that you must adhere to with respect to
designating allele symbols:
• if you are using upper and lower case letters, the upper case
always symbolizes the dominant allele
• a (+) superscript, always symbolizes the wild-type allele -assuming that you have a reference point that indicates what
phenotype is wildtype and what is mutant
a wild-type allele is often, BUT NOT always
dominant
 make no a priori assumptions regarding the
dominance of a wild-type allele
17
The Gene Name Game
Nature 411: 631 2001
The complex, confusing,
sometimes amusing and
often intimidating world of
gene names
18
The naming of genes: Drosophila style
http://tinman.vetmed.helsinki.fi/eng/drosophila.html
19
pop culture quiz :
question 1
Like many Drosophila genes,
the tinman gene is named for
its mutant phenotype.
What structure is missing in a
fly with a mutated tinman
gene?
20
lots of genes are named for their
“loss-of-function” phenotypes
[OK, we’re all adults here]
question 2: what structure(s) are missing in flies mutated in
the ken and barbie gene?
21
Don’t believe there is a gene with this name? Check it
out at the Interactive Fly:
http://www.sdbonline.org/fly/genebrief/ken&barbie.htm
Zebrafish geneticists are not immune to this gene
naming weaknesses:
nicotine response genes (hbog and bdav) named for
these two people:
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Gene names:
clever, obscure and often downright bad
23
Nettie Stevens was a talented cytogeneticist who
discovered heteromorphic chromosome pair in insects.
She was the first to propose that the X and Y -bearing
sperm determined the sex of the zygote.
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The Drosophila heteromorphic pair consists of the X and
the Y chromosome: They synapse and segregate during
meiosis like autosomal homologs
 Implicit in our analysis of Morgan’s crosses is the idea
that sex chromosomes segregate into different gametes as
paired homologs would
 But Morgan suggested that these chromosomes do not
carry the same genes -- so why or how do they pair in
meiosis?
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Sex chromosomes can be divided into two regions
Pairing: region of genetic homology where pairing occurs during
meiosis
Differential region: non-homologous region  genes in this
region have no counterpoint on the other sex chromosome
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Hemizygous: genes located in the differential
region of the X chromosome are hemizygous in males
because males only have one copy of the gene
Human X (left) and Y
chromosomes
Nature 423: 810 June 19, 2003
Tales of the Y chromosome
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Gene and DiseaseMapView of autosomes, X & Y chromosomes
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gnd&part=A272
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View of Homo sapiens genome
http://www.ncbi.nlm.nih.gov/projects/mapview/map_search.cgi?taxid=9606
Gene and DiseaseMapView of autosomes, X & Y chromosomes
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gnd&part=A272
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Chromosomal Sex-determining Mechanisms
Organism
Female
XX
• Mammals
• Some
amphibians and
reptiles
• Many insects
such as the
fruitfly
Drosophila
• Some plants
with male and
female sexes
Male
Comments
XY
Males produce two
different types of sperm:
50% carry an X
chromosome and 50% a
Y chromosome
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Organism
female
male
Comments
Some insects (including
spiders)
XX
XO
Y chromosome is absent.
Males have a single X
chromosome and produce two
different types of sperm: 50%
bearing an X chromosome and
50% with no sex chromosome
Some roundworms
-such as
Caenor
habditis
elegans
Pattern of sex linkage same
as XX, XY species
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Organism
female male Comments
• Birds
ZW
ZZ
• Some insects such
as moths and
butterflies
• Some amphibians
and reptiles such as
KOMODO dragons
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By convention, Z and W are
used to indicate the sex
chromosomes in these
species. The Z chromosome
is equivalent to the X
chromosome. Females
produce two different types
of eggs: 50% carry the Z
chromosome and 50% carry
the W chromosome.
Organism
female
male
Bee, wasps and ants
(Hymenoptera)
diploid
haploid
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Comments
Males usually develop from
unfertilized eggs; females
from fertilized eggs. There
are no sex chromosomes
per se
Why are there so many different
mechanisms of genetic sex
determination?
What do you know about
non-genetic sex-determining
mechanisms?
35
In many lineages, the primarily Sex Determining signal
evolved from an ancestral environmental signal (probably
TSD) into a diverse array of genetic mechanisms – as
illustrated in the previous slides
Current Biology 16, R736–R743, September 5, 2006
36
Where did the X and Y come from?
Genes in the NRY, or nonrecombining
region of the Y (blue in diagram), have
helped reveal the evolutionary history of the
X and the Y. The region is so named because
it cannot recombine, or exchange DNA, with
the X. Only genes that still work are listed.
About half have counterparts on the X (red);
some of these are “housekeeping” genes,
needed for the survival of most cells. Certain
NRY genes act only in the testes (purple),
where they likely participate in male fertility.
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The dis’d (disrespected Y chromosome
“….Until recently, the Y chromosome seemed to fulfill the role of
juvenile delinquent among human chromosomes -- rich in junk,
poor in useful attributes, reluctant to socialize with its neighbors
and with an inescapable tendency to degenerate. …….
quote from Nature August 14, 2003
HUH what does this mean? This question is serious.
Want to know more? Check out this Scientific American article:
Why is the Y so weird?
http://fire.biol.wwu.edu/trent/trent/WhyYweird.pdf
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The X & Y chromosomes originated a few hundred million years ago
from the same ancestral autosome.
Y then is the Y a shadow of its former self?
The functionally specialized Y chromosome highlights two evolutionary
processes that are thought to have produced the mammalian chromosome:
• genetic decay
• accumulation of genes that specifically benefit male fitness
Huh? Genetic Decay?
About 300 million years ago the mammalian X and Y chromosome probably
looked a lot like a pair of homologous autosomes*
(300 million years = paleozoic/mesozoic/cenozoic?)
before/during/after dinosaurs?)
* the Z & W sex chromosomes evolved independently from a different set of autosomes
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Sex chromosomes
(in birds and
mammals) are
thought to have
evolved
independently from
what were 300
million years ago a
“regular” pair of
chromosomes
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•
•
•
•
•
The loss of genes in the Y chromosome probably resulted from a
series of events which included:
Evolution of the male-determining SRY gene from a gene (called SOX) found
on both ancestral chromosomes (the X chromsome still carries a copy of this
gene)
Chromosomal rearrangements occur between the ancestral chromosomes:
progressive loss of recombination between increasingly larger segments of the
ancestral X and Y chromosomes [due to structural rearrangements of the Y
chromosome that inhibited pairing and crossing-over with the X]
Ancestral Y starts to accumulate mutations: loss of recombination meant that
on the evolving Y chromosome mutations accumulated in genes-- these
mutations couldn’t be purged by recombination with a homolog (see diagram
below)
Over millions of years, the number of functional genes on the Y chromosome
declines dramatically
Due to this genetic decay the non-recombining region of the human Y
chromosome has retained only about 3% (19/ 664) of its ancestral autosomal
genes
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BUT why didn’t the X chromosome decay?
42
Mutations on the
evolving X
chromosome
could be purged
by recombination
that occurred
during meisois in
female animal
+ = wildtype
allele
a, b = deleterious
mutation
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Gene Score Card
Sort the Y linked genes into three categories:
1. Genes in the pairing region (synapsis and crossing-over during
prophase of meiosis I occurs here): about two dozen (29 to be
exact) ancestral genes are found on both the X and Y
chromosome in this region
2.Residual ancestral genes in the non-recombining region (are
also on the X chromosome): 19 genes
3.Genes required for male sex-determination (Sry) and male
fitness (not represented on the X chromosome): at least several
genes
• male fertility genes include those required for normal
spermatogenesis (infertile men have deletions of specific
regions)
NATURE |VOL 434 | 17 MARCH 2005
44
Speculative map of the Y
chromosome showing
genes related to male
“fitness” that have may
accumulated on the Y
chromosome
From less politically correct days:
Science 261: 679 August 6, 1993
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Y-linked genes in other species
• Male (top) guppy with colorful ornamentation – thought
to enhances sexual attraction but tradeoff is increased
visibility to predators
• Female (bottom) does not exhibit bright colors -apparently for female, the colors do not enhance
attractiveness to potential mates enough to overcome
increasing visibility to predators
• This trait is know to be Y-linked
•
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Annual Review of Genetics 42: 565 2008
Degeneration of the sex-specific element (Y or W)
from an original autosome (purple) to form more
or less differentiated XY (blue) or ZW (pink) sex
chromosome pairs. Degraded Y chromosomes
harbor male-specific genes (blue lines) and W
harbor female-specific genes (pink lines).
Examples of vertebrate species that exhibit this
level of differentiation of XY or ZW chromosomes
are given on the left or right, respectively. Dotted
lines represent pairing and recombination.
Note that mole voles have dispensed with the Y
chromosome completely – presumably this species
SRY-gene-equivalent is on an autosome.
What about the human Y – will it eventually erode
altogether? Some say yes, others disagree. See:
The human Y chromosome is here to stay: it has
lost only one gene in the past 25 million
years……
http://fire.biol.wwu.edu/trent/trent/Yheretostay.pdf
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Some major transitions (indicated
by yellow band ) in the sexdetermining system of higher
vertebrates. A chromosome (turtle
5) that was originally an
autosome in TSD reptiles
acquired a role as ZW in sex
determination in birds ( green),
possibly by means of candidate
gene DMRT1. The same (green)
chromosome is involved in sex
determination by multiple XY
chromosome in the platypus. And
a completely different
chromosome pair (blue,
represented by turtle and chicken
4, platypus 6) assumed a sexdetermining role as a new
XY in therian mammals as SRY
evolved from ancient gene SOX3.
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