Download Y chromosome

Biology 321
 The inheritance
patterns discovered by
Mendel are true for genes
that are located on
autosomes
 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
 What do the inheritance patterns of sex-linked traits look like?
 First look at experiments done in the early 1900’s by a fruifly
geneticist named Thomas Hunt Morgan
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 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
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
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?
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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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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.
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.
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
A male Drosophila fruitfly performs a ‘wing threat’, typical aggression
behaviour, towards a rival male. Liming Wang and David Anderson
show that the volatile pheromone cVA promotes male-to-male
aggression by activating olfactory sensory neurons expressing the
receptor protein, Or67d. This work opens the study of aggressive
behaviour to detailed genetic manipulation and investigation.
Cover image: Liming Wang & Michael Maire, Caltech.
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One way a male Drosophila
shows aggression is by
"lunging," in which it rears up
on its hind legs and snaps
down with its forelegs on its
opponent. (Credit:
Caltech/Liming Wang and
Michael Maire)
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
What does heteromorphic mean?
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prophase of meiosis I in the testis of a salamander
 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 pair
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 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
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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?
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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
InteractiveFly:
http://www.sdbonline.org/fly/genebrief/ken&barbie.htm
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Gene names:
clever, obscure and often downright bad
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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
 make no a priori assumptions regarding the
dominance of a wild-type allele
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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
Shaded cells = diploid animals
Organism
Female Male
• Mammals
XX
• Some
amphibians and
reptiles
• Many insects
such as the
fruitfly
Drosophila
• Some plants
with male and
female sexes
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)
• Some
roundworms
(such as
Caenorhabditis
elegans)
XX
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
Pattern of sex linkage
same as XX, XY
species
XO
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Organism
female male Comments
• Birds
ZW
• Some insects
(such as moths
and butterflies)
• Some
amphibians and
reptiles such as
KOMODO
dragons
ZZ
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.
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Organism
female
male
Comments
Bee, wasps and
ants
diploid haploid Males usually develop
from unfertilized eggs;
females from fertilized
eggs. There are no sex
chromosomes per se
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What about non-chromosomal sex-determining
mechanisms?
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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 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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The dis’d (disrespected) Y chromosome:
quote from Nature August 14, 2003
“….Until recently, the Y chromosome seemed to fulfil 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. …….
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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Sex chromosomes
(in birds and
mammals) are
thought to have
evolved from what
were 300 million
years ago a
“regular” pair of
chromosomes
Th
e
los
s
of
ge
ne
s
in
th
e
Y
ch
ro
m
os
a
ome probably resulted from
series of events which
included:
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• 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 chromosomal inversions that
inhibited crossing-over]
• 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
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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Speculative map of the Y chromosome
Science 261: 679
from less politically correct days: August 6, 1993
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