Biology 321
Ì The inheritance
patterns discovered by
Mendel are true for genes
that are located on
autosomes
Ì What is an autosome?
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The fly room at Columbia University ~ 1920
l to r: Calvin Bridges, A. sturtevant, Thomas Hunt Morgan
Early 20th century fly guys
Ì What do the inheritance patterns of sex-linked traits look like?
Ì First look at experiments done in the early 1900’s by a fruitfly
geneticist named Thomas Hunt Morgan
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Ì 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
Ì
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
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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
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MEANWHILE back to MORGAN’S experiments
[we will work through the crosses on the board]
Ì 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
Ì 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
Ì This will almost always be true if the gene for the trait is located on an autosome
Ì Morgan interpreted the results of these crosses using information that he had about the
chromosome constitution of Drosophila
Ì 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
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Ì 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
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Ì A Drosophila male has an X and a Y chromosome
Ì These X and Y chromosomes synapse and segregate during meiosis I
like autosomal homologues would.
Ì 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
Ì Thus females would have two copies of the gene and males would
have one copy
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Ì Assigning allele symbols
Ì 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
Ì 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
Ì Fill in the genotypes of the reciprocal crosses: use Xw+ for red, wild-type
allele and Xw for white allele.
Ì 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
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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
Ú make no a priori assumptions regarding the
dominance of a wild-type allele
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The Gene Name Game
Nature 411: 631 2001
The complex, confusing,
sometimes amusing and
often intimidating world of
gene names
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The naming of genes: Drosophila style
http://tinman.vetmed.helsinki.fi/eng/drosophila.html
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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?
15
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?
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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
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http://www.genenames.org
19
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
Ì Implicit in our analysis of Morgan’s crosses is the idea
that sex chromosomes segregate into different gametes as
paired homologs would
Ì 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 à 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
Cannabis
sativa: XX
females and XY
male plants
* While the taxa listed have XX & XY chromosomes, the primary sex-determining signal varies.
For example in humans, sex is determined by the presence or absence of the Y-linked SRY gene.
But, in Drosophila, sex is determined by the number of X chromosomes.
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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?
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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
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Where did the X and Y come from?
Clues from the present-day mammalian Y
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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Y is the Y a shadow of its former self?
About 300 million years ago
the mammalian X and Y chromosome
probably looked a lot like a regular pair of
homologous autosomes*
(300 million years = paleozoic/mesozoic/cenozoic?)
before/during/after dinosaurs?)
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
* 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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Huh? Genetic Decay?
BUT why didn’t the X chromosome decay?
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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
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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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