Chromosomes

Genes are linear sequences composed of nucleotides G,A,T(U), C.

Genes are strung together in much larger strings called chromosomes.
Chromosomes, which hold many genes, can be circular (as in bacteria)
or linear (as in eukaryotes)
 Humans have 22 pairs of autosomal
chromosomes and one pair of sex
chromosomes (either XX or XY).

Females: 1-22 + XX

Males: 1-22 + XY

There are approximately 30,000 protein

coding genes scattered across these
chromosomes.

For each chromosome, one is maternal,

one is paternal

1M, 1P
2M, 2P
3M,3P
etc…

22M,22P
And then either
X/X or X/Y
Examples of
chromosome
numbers in
various
organisms
Table here shows
range of 1 to 216
It is not clear what
importance these
numbers have, if any.
Transmission of Chromosomes:
Mitosis
During G1 the cell is diploid
and contains 2 copies of
each chromosome (1
maternal, 1 paternal)
Cell
At S phase (synthesis),
Cycle chromosomes are
replicated so that now there
are 4 copies of each (2
maternal, 2 paternal)

After mitosis (cell division)

the cell distributes the four
copies into two daughter
cells, each of which are
again diploid with 2 copies
(1 maternal, 1 paternal)
(diploid)
 Mitosis itself is divided into four phases defined by what
the chromosomes are doing.

P: prophase -chromosomes thicken

M: metaphase -chromosomes line up
A: anaphase -chromsomes pull apart
T: telophase -chromosomes go to nuclei of two cells

Notes on mitosis:
--cell doesn’t ‘know’ its going through PMAT, those are just named by us
--separation in anaphase is quick, as though the chromosomes are under
tension prior to being pulled to the poles
--each daughter cell retains one set of maternal chromosomes and one
set of paternal chromosomes
--in mitosis there is no recombination, no synaptonemal complex
--some movies of cell division can be seen at
http://www.bio.unc.edu/faculty/salmon/lab/mitosis/mitosismovies.html
Complete
Mitotic Cycle
P

A
 Transmission of Chromosomes:
Meiosis
Meiosis is the process by which chromosomes are delivered into gametes
for fertilization. During fertilization two haploid gametes are joined to make
a new diploid cell (zygote).

Chromosome content during meiosis

Start with 2 copies of each chromosome (1 maternal, 1 paternal)

DNA replication copies each chromosome (2 maternal, 2 paternal)

Meiotic recombination mixes up maternal and paternal chromosomes to

make new hybrid/chimeric chromosomes.

The first meiotic cell division distributes those chromosomes into two cells
(2 chromosomes each).

The second meiotic cell distributes those (2) chromosomes into two cells (1
chromosome each). This is the final, haploid gamete.
Process of
spermatogenesis
and oogenesis
Replication
Meiosis I
Meiosis II
Differentiation
Complete
Meiotic Cycle
Transmission of Parent
the A and a alleles
A/a B/b
of gene A and the B
and b alleles of
gene B during
meiosis.
Genes A and B are on We do not yet
different discuss meiotic
recombination in
chromosomes. this example.
As a result of random
sorting/segregation….
A sorts with either B or
b.
a sorts with either B or
b. Gametes
This explains the 9331 AB ab Ab aB
Mendelian ratio.
 Parental
Chromosomes Chromosomes Sort
Recombine during Randomly (depicted in
previous slide)
Meiosis
 A whole slide-full of notes on meiosis:

--meiosis involves reduction of chromosome (gene) number to a haploid level

--meiosis involves synaptonemal complex formation and meiotic
recombination. This produces chromosomes that are hybrids or chimeras of
the original paternal and maternal chromosomes in that parent. This means
the parent does not give exactly the same assortment of alleles it itself has.
--meiosis involves random sorting/segregation of genes and chromosomes
into the gametes so you don’t get all maternal all paternal.
--in females meiosis begins before birth but stalls until puberty. Thus the first
complete meiosis in human females takes some 13 or so years to complete.
Afterwards it reinitiates to make one oocyte at a time per month finishing
decades later. In males meiosis begins at puberty and proceeds continually.
--in females only one of the four possible haploid gametes will turn into a
‘good’ oocyte. The others are ‘discarded’ as polar bodies. In males all four
meiotic products are functional spermatozoa.
--in terms of actual chromosome numbers, meiosis involves the following
process: 2N—4N—2N—1N. However, the chromosome content in meiosis
can also be described in terms of the number of chromosomal structures
observed in the microscope. In that case it appears more like 2 to 1.
--Pairing of chromosomes during meiotic recombination is important. The
presence of unpaired chromosomes usually causes sterility.
Side-by-side comparision of mitosis and meiosis that is quite
nice but unfortunately supplied by the publisher in such an
awkward and small format that it can only be appreciated at
home with a powerful zoom lens.
 Diploid Life Cycle
(as Mendel suggested)

2n Adult Female 2n Adult Male

Meiosis Meiosis

many mitosis
many mitosis

XXX
1n 1n 1n 1n gametes 1n 1n 1n 1n gametes

2n 2n
zygote zygote
(female) (male)
For your consideration:

For human beings, every unique individual has a unique combination of alleles.
There are about 30,000 genes. Each person can have up to two alleles at each of
those genes. For instance at gene A, mom could be Allele1 and Allele2, dad
could be Allele3 and Allele4. So, a kid could be either A1A3, A1A4, A2A3, or
A2A4.

Our phenotype depends on the allele collection received from our parents, e.g.,
A1 A3 and B6 B2 and C7 C8 and D3 D3 and E3 E4 and on and on. The alleles in a
genome usually produce proteins and RNA, and during development they make
me me and you you. That is a very complex problem. But we know that if you
have the exactly the same alleles you get the same output (i.e. identical twins).

Questions about what happens during meiosis...

*Suppose there was NO meiotic recombination but maternal and paternal chromsomes
still segregated randomly during meiosis. How many different types of offspring would be
possible from a set of parents?
*Suppose there was no meiotic recombination and chromosomes did NOT segregate
randomly, i.e. gametes got either all paternal or all maternal chromosomes from each
parent. How many different kids then?
*If two of your own gametes, produced in normal meiosis, fertilized themselves and then
developed, would it make you again?
*Are brothers/brothers, brothers/sisters, sisters/sisters 50% genetically identical to one
another, 25%, 75%, some other value altogether, some range of values?
 Sex Determination Systems
Sexual Reproduction
Combines genomes from two separate individuals. The individuals are of
the same species but are opposite mating types
Why, What Purpose?
Generation of unique allele combinations (individuals) is achieved by
joining the recombined maternal and paternal alleles from each of two
mating types. This generates individual variation adapted to the rate at
which things change on this planet. If not for meiosis, recombination, and
sex, organisms would be very similar to their parents and would not change
much from generation to generation to generation (except for a low rate of
DNA mutation). Sex and meiotic recombination is like constantly shuffling
a deck of 30,000 cards from each parent. The chance of one hand being the
same as another is pretty small.
Mating Types
Organisms typically come in two mating types (+, -; female, male).
Organisms of opposite mating type combine their DNA to produce offspring.
This involves joining the products of two separate meiosis. That is, the
recombined genome from one mating type fertilizes with the recombined
genome of the other mating type.
 Sex Determination Systems
Humans, etc: The male chromosome Y has a gene testis-determining factor
(TDF/SRY) that dictates a male differentiation pathway. So, if you have a Y
chromosome you develop into a male. If you don’t have a Y (that is you are XX), you
develop into a female.

Note that genes on the X chromosome are present in 2 copies in females and only 1
copy in males. This might mean that there is double the amount of X gene proteins in
females than in males. However, a process called dosage compensation, or X-
chromosome inactivation, causes one or the other of the X-chromosomes in female
cells to be inactivated (into a structure called a Barr body). Thus, each cell has only
one active X chromosome, just as in males.

Chromosome abnormalities for sex chromosomes occur in humans and are

discussed in the text. These include…
Turner syndrome: XO
Klinefelter syndrome: XXY (also XXXY, XXYY)
XYY syndrome
XXX (triplo-X)
Typically the extra X are inactivated just as in normal XX females

Because the alleles on the two X chromosomes in females are not necessarily
identical, random inactivation of one X chromosome or the other during female
development can lead to a variety of effects. One of the most famous is the calico
(spotted) fur coloration on female calico cats.
A calico cat is a cat with a
particular type of coloration.
Suppose you were shown a
male calico cat. What might
the explanation be?
 The way sex determination works in humans is not
particularly special or universal.
Drosophila (fruit fly)
This organism also has X and Y chromosomes, but sex determination works a
bit differently. Here the system is due to a so-called X-chromosome-autosome
balance system.

--If a fly is XX or even XXY it will be a female because its X chromosome to

autosome chromosome ratio is 1
--If a fly is XY or XO it will be male because the X chromosome to autosome
ratio is 0.5

Summary
XX female flies (2X:2A)
XY male flies (1X:2A)
XXY female flies (2X:2A)
XO male flies (1X:2A)

C. elegans (a soil nematode)

In this nematode there is an XX and XO system. If you are XX you are a
hermaphrodite, which means that you are both male and female and can fertilize
yourself. If you are X0 then you are male.
Sex determination in Drosophila
Plants (all kinds of variations occur here)

Possibilities…asexual altogether, separate male plants and female

plants, plants with male and female flowers or plants with flowers
that are both male and female. In addition, some plants change
flower sex from juvenile to adult or during the growing season. E.g.,
squash flowers are typically male early and female later. Plants are
ancient and display all kinds of unusual characteristics.

“Gardeners often become concerned when many

flowers appear early but fruits fail to set. The reason
for this is that all of the early flowers are males.
Female flowers develop somewhat later and can be
identified by the miniature fruit at the flower base. In
hybrid varieties of summer squash, however, the first
flowers to appear are usually females and these will
fail to develop unless there are male squash flowers -
and bees - in the nearby area.”
From http://vric.ucdavis.edu/pdf/FruitSetProblems.pdf
Environmental sex determination
(some reptiles)

One example: If development occurs

at < 28 degrees celsius, animals
are male, if development occurs
between 28 and 32 degrees,
animals are a mixture of males and
females, and if development
occurs at > 32 degrees, animals
are female

Honeybees

Diploid organisms are female

If given a special diet these can turn
into queens (i.e. what you eat
makes you what you are)
Otherwise they are the worker bees

Haploid (unfertilized) organisms are

male. These become drones that
fertilize the queen
Nemo, of ‘Finding
Nemo’ fame Developmental Sex Change
 Inheritance of X-linked Genes
Genes that are on the X chromosome (that is, X-linked) display somewhat
different patterns of inheritance in males and females.

Basically the expected patterns of dominance and recessiveness for X-

linked genes play out a bit differently in males and females as compared to
autosomal genes.

To examine this phenomena we will look at X-linked inheritance in flies

Model:
w+ is the allele for normal RED eyes (called normal, or wildtype).
It is dominant.

w is an allele of the w+ gene. It causes white eyes due to a failure to make

pigment. It is recessive.
Transmission of
model sex-linked
trait in Drosophila
starting with
White eyed-male
Homozygous red
eyed-female
Transmission of
model sex-linked
trait in Drosophila,
next generation
Starting point reversed….
White eyed-female, Red eyed-male
 Meiotic Nondisjunction
A situation where chromosomes fail to segregate
properly in the two daughter cells
--normal
--nondisjunction in meiosis I
--nondisjunction in meiosis II
Genetics of a
nondisjunction
event with X-
linked red
eye/white eye
model
 Type of experiment that reveals nondisjunction events

MATING: Xw Xw x Xw+ Y
Normal gametes should be Xw and Xw from the mother and Xw+ and Y from the
father.
Once in a while gametes might be Xw Xw and 0 as a result of nondisjunction
in the female. These, together with normal male games, either Xw+ or Y,
would give F1 flies as follows…
Xw Xw Xw+ --dies (cant have too many X)
Xw Xw Y --white female
O Xw+ --red male (sterile)
O Y --dies (need at least one X)
This is what the previous few slides show you.

However, in an experiment almost all the offspring are actually normal…

½ red female
½ white male

Only if you were to screen enough progeny (an advantage of using flies) you
might on occasion observe a meiosis in which nondisjunction events had
occurred. So, in a large population a few, super rare, flies would be

Xw Xw Y --white female
O Xw+ --red male (sterile)
Example of an X-linked trait in humans
Red-Green color-blindness

8 or 3?
Hemophilia, an X-linked
disorder present in royal
families of Europe
Notes on X-linked recessive inheritance in humans

1. in pedigrees, number of affected males usually greater than affected

females (only one copy of gene needed to cause disorder)
2. sons of carrier females (heterozygous for the mutation on the X
chromosome) will have 1:1 ratio of normal to affected individuals
3. daughters of carrier females will have 1:1 ratio of normal to carrier
4. offspring of affected male with normal female will be all normal males,
all carrier females
5. most but not all X-linked recessive disorders (and other recessive
disorders) are generally RARE

There are relatively few X-linked dominant disorders

Y-linked conditions are rare (very few genes on the Y chromosome)

Take a look at OMIM (online mendelian inheritance in man).

This is a public website with information on human diseases.
http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim
search for interesting term, like ‘toe’
The following is an interesting interactive website
http://www.hhmi.org/biointeractive/gendertest/gendertest.html
“Gender Testing of Female Athletes”