WJL Intro and Topic 1 - Chrom Trans Eukaryotes (Student)
WJL Intro and Topic 1 - Chrom Trans Eukaryotes (Student)
WJL Intro and Topic 1 - Chrom Trans Eukaryotes (Student)
LSM2105
Course Introduction
&
Topic One: Chromosome in Eukaryotes
WU Jinlu
https://www.polleverywhere.com/mobile
Responding via the web
During class, I will display a Poll Everywhere activity on-screen
on a web address: PollEv.com/wujinlu From your phone, laptop,
or tablet you can enter the web address and will be taken to a
screen that allows you to respond to the activity.
4
Genotype vs Phenotype
Complex traits such as eye color are the products of many genes working
in concert.
https://www.quantamagazine.org/omnigenic-model-suggests-that-all-genes-affect-every-complex-trait-
20180620/ 5
We must be able to
explain Genetics from
both nature and
nurture perspective.
6
Epigenetics
7
Genetics Without the “Epi” Prefix Is Incomplete
8
How a scholarly spat shaped genetic research
Sem I Sem II
Features of DNA & RNA
A/P Cynthia He A/P Liou Yih Cherng Advanced Genetic
Block S1A Level 6 Block S3 Level 6 Methods/Technologies
Tel: 65167377 (office) Tel: 65167711 (office) Model organisms in
E-mail: dbshyc@ E-mail: dbslyc@ Genetics
……
Sem I & II
A/P Chew Fook Tim
Mendelian Genetics,
(Module Coordinator)
Population Genetics,
Block S2, Level 5
Quantitative Genetics
Tel: 65161685 (office)
…..
Email: dbscft@nus.edu.sg 12
Lecture / Tutorial (Will be webcast and recorded)
ek Month
Tue, 10-12pm, LT26 Thu, 10-12pm, LT26
Orientation: Mon, 7 Aug – Sat, 12 Aug 2023 (1 week)
15 Overview of Genetics & Chromosome 17 Cellular Division: Mitosis and Meiosis; Non-
Aug in Eukaryotes (WJL, Section 1) Disjunction and Polyploidy (WJL)
22 Chromosome in Prokaryotes, Genetic
24 Chromosome Compaction, Structure, Organizat
Transfer and Mapping Analysis in
(WJL)
Microorganisms (WJL)
29 Chromatin Remodeling and Gene
Dr Wu Expression (WJL)
31 Chromosome Recombination (WJL)
+5% PeerWise
09 Quantitative Genetics – Statistical Description of
Nov Genetics – Mutation & Selection Forces;
Maintenance of Polymorphism (CFT)
Quantitative Traits (CFT) A/P Chew
assignment
14 Quantitative Genetics – Polygenic 16 Continual Assessment 3 (fixed date and time, fac
Inheritance, Heritability, Breeding,
Heterosis (CFT)
face test, no replacement test) (CFT, Section 3 only,
CA3 20%
All contents
OPEN book test – hard copy, no internet)
Reading Week: Sat, 18 Nov – Fri, 24 Nov 2023 (1 week)
Final Examination: Tue 5-Dec-2023, 9am (fixed date and time, face to face exam, CLOSED book, fixed date
40% Final time, no replacement exam) (All Sections included, All MCQs); venue to be announce later by Registrar’s Of
(and updated at the course Canvas site) 13
Vacation: Sun, 10 Dec 2023 -Sun, 14 Jan 2024 (5 weeks)
https://peerwise.cs.auckland.ac.nz/home/
Weekly
Timeline
Course ID 26240
The deadline is at
11:59pm on Sundays, LSM2105AY2324SemI
(Topics 1 & 2 on 27th
Aug, Topic 3 & 4 on
Your participation will contribute 5% to your final module grade
10th Sept 2023.
Wait for the details to be announced
5 marks: 4 MCQs+5 Answers+5 Comments 14
What & Why students do?
Ownership of Learning; Peer Learning; Collaborative Learning, Self-directed Learning
Pearson’s correlation coefficient between examination scores and students’ accomplishment on
PeerWise
No. of questions No. of answers No. of correct No. of comments No. of ratings
Academic Year and Semester
authored submitted answers submitted submitted
Total reputation Total answer Question authoring Question answering Question rating
Academic Year and Semester Badge scores
scores scores component component component
AY18/19 Sem I .355** .189** .327** .248** .209** .342**
AY18/19 Sem I .199** .138 .179* .132 .191** .200**
AY19/20 Sem I .353** .263** .262** .245** .226** .365**
AY19/20 Sem II .420** .334** .298** .316** .398** .221**
AY20/21 Sem I .316** .310** .170** .313** .274** .190**
AY20/21 Sem II .235** .104 .182* .119 .142 .175*
15
How I am going to teach?
I am not a commander
Assimilation but not Transmission
16
Climbing Mountains Together
Facilitating Motivating
https://starsandjars.com/2019/02
/18/the-jar-of-life-a-story/
18
Happy Journey
19
What I am going to teach?
Four Topics on Chromosome
Chapter 3 Chapter 2
Topic 1: Intended Learning Outcomes (ILO) and Threshold Concepts
Threshold Concepts:
22
Topic 1: Learning Plan
• Practice Learning
• Measure Learning
Constructive Alignment 24
Online Quizzes/Track learning Qs (not graded)
25
Chromosomes
GENERAL FEATURES OF CHROMOSOMES
28
Please watch the two short videos on YouTube before lecture
1. https://www.youtube.com/watch?v=7NM-UWFHG18
Cell Cycle and Mitosis (must watch)
1. https://www.youtube.com/watch?v=jjEcHra3484
Meiosis - Plants and Animals (must watch)
29
Cell Cycle and Mitosis
https://www.youtube.com/watch?v=7NM-UWFHG18
30
Cell cycle in eukaryotic cells: the sequence of growth and
division of a cell; consists of Interphase (G1, S, G2), Mitosis
(nuclear division), and Cytokinesis (cytoplasm division)
Interphase = G1 + S + G2
Cells in G0 are in a non-
dividing phase
Mnemonic to
remember the order:
I Proudly Prefer Milk
And Tea 32
33
Interphase (G1, S, G2)
34
Chromatid vs Chromosome
35
0.5 µm Chromosomes DNA molecules
One chromosome,
One DNA molecule
Chromo-
Chromosome
some arm
duplication
(including DNA
synthesis)
Centromere
One chromosome,
Two DNA molecules
Sister
chromatids
Separation of
sister chromatids
Centromere
One chromosome,
One DNA molecule
Sister chromatids per cell 36
• Note that at the end of S phase, a cell has twice
as many chromatids as there are chromosomes in
the G1 phase
– A human cell for example has
• 46 distinct chromosomes in G1 phase
• 46 pairs of sister chromatids after S phase
• Therefore the term chromosome is relative
– In G1 and late in the M phase (mitosis), it refers
to the equivalent of one chromatid
– In G2 and early in the M phase (mitosis), it
refers to a pair of sister chromatids
37
Phases of Mitosis
38
Mitosis is subdivided into five phases
(PPMAT)
– Prophase
– Prometaphase
– Metaphase
– Anaphase
– Telophase
39
Prophase
• Chromatin condenses
into chromosomes.
• Nuclear envelope
dissociates into smaller
vesicles
• The mitotic spindle
apparatus/mitotic
spindle starts forming
40
Prometaphase
• Centrosomes move to
opposite ends of the cell and
demarcate two spindle
poles.
Kinetochore
42
Mitotic Spindle Apparatus
Metaphase
• Pairs of sister
chromatids align
themselves along a
plane called the
metaphase plate
Equator
• Each pair of chromatids
is attached to both poles
by kinetochore
microtubules
44
How chromosomes are able to line up at the metaphase plate?
Thinking
???
Prometaphase Metaphase 45
How opposing forces may drive chromosomes to the
metaphase plate?
(Counter force balance model and Bipolar force balance model)
Expt Conclusion
Interpolar
or astral
microtubule
46
http://www.ncbi.nlm.nih.gov/books/NBK26934/
Basics of Motor proteins FYI
Head domain
Tail domain
47
Dynamic instability of microtubules
Polymerization
De-polymerization
• All chromosomes
must align on the
metaphase plate
49
Anaphase
50
ThePenguinProf: Cell Cycle and Mitosis
51
Mechanical force in the segregation
+
2 +
1 kinesin
1) A sliding force is generated btw overlap microtubules from opposite poles to push
the poles apart;
2) Aster microtubules attach to cell membrane, when cell elongates, a pulling force 52
acts directly on the poles to move chromosomes apart
Anaphase A chromosome movement
54
a) Hill sleeve model: kinetochore–
microtubule bonds are arranged in FYI
series and require nearly synchronous Affinity force
detachment and re-attachment of all
bonds for relative movement of the
microtubule and the kinetochore.
c) Non-motor kinetochore–microtubule
coupler model: flexible non-motor
proteins, Ndc80, bind to and detach
from the microtubule independently
from one another and serve as dynamic
couplers between the kinetochore and
the spindle microtubules. 55
Spindle pole separation in anaphase B.
56
Spindle pole separation in anaphase B.
When this plus end directed
motor protein move to plus
Direction of move
end of astral microtubule, it
brings entire centrosome and
also the chromosomes move
to the cell cortex.
Cell cortex
57
Nondisjunction
58
Telophase and Cytokinesis
• Chromosomes reach
their respective poles
and decondense
• Nuclear membrane
Contractile ring
reforms to form two (myosin and actin)
separate nuclei
60
http://www.youtube.com/watch?v=VlN7K1-9QB0&feature=related
Summary
of mitosis
Cell cycle (cell-division or cycle reproductive): the orderly sequence of events by which a
cell duplicates its contents and divides into two.
The M phase (cell division) includes various stages of nuclear division (prophase,
prometaphase, anaphase, and telophase), and also cytoplasm division (cytokinesis),
which overlaps the final stages of mitosis.
Chromosome set (n): The chromosomes of a haploid genome. Sperm and egg cells carry a
single chromosome set and are said to be haploid (they have n chromosomes and a DNA
content of C). For human cells, n=23 and C is about 3.5 pg.
Mitosis maintains the cell's original ploidy level (for example, one diploid 2n cell producing
two diploid 2n cells; one haploid n cell producing two haploid n cells; etc.).
61
Summary
of mitosis
62
Key Concepts of mitosis
Kinetochore–microtubule interactions
63
Move beyond the syllabus FYI
64
MEIOSIS
Meiosis I and II
65
Cell Cycle and Mitosis
https://www.youtube.com/watch?v=jjEcHra3484
66
MEIOSIS
Germline Cells
(Germ Cells in Gonads)
Gametogonium
(plural gametogonia)
(2n)
(mitosis)
Spermatogenesis / Oogenesis
(meiosis)
Sperm / Egg
(gametes, n) 67
Sister Chromatids vs Homologous Chromosomes
69
Meiosis I
Prophase I
Homologous maternal and paternal chromosomes pair, synapse, and exchange genetic
information (by homologous recombination), forming at least one crossover per
chromosome
Chiasma is to
establish physical
connections
between
homologous
chromosomes,
thereby ensuring
accurate
Tetrad chromosome
segregation and
producing
haploid germ cells
Microtubules Mediate
Meiotic Pairing and Synapsis
KASH-
Zygote defective protein 12
This simple model of a nucleus with only one pair of chromosomes illustrates the process of synapsis
The chromosomes attached by their pairing centers to proteins on the nuclear envelope,
which are linked to the cytoskeleton of the cell. The microtubules in the cytoskeleton
facilitate movement of the protein complex and associated chromosomes, promoting
encounters between chromosomes. Once the chromosomes come together, a protein
called dynein assesses whether or not the chromosomes are homologous and, if yes
(means that affinity force btw the pairing center is stronger than dynein force), allows
formation of a zipper-like synaptonemal complex between the two. If no (means that
affinity force btw the pairing center is weaker than dynein force, they are not homologues),
the dynein force will drive them apart, and searching homolog continues.
75
It takes two to tango
An analogy to teach biology concept
A short video clip from the movie “Scent of a Woman” (starring Al Pacino)
76
STAGES OF PROPHASE OF MEIOSIS I
Chiasma is to
establish physical
connections
between
homologous
chromosomes,
thereby ensuring
accurate
Tetrad chromosome
segregation and
producing
haploid germ cells
1. Proteins complex (red dots shown on slide is the study from C. elegans) binds
to chromosome ends to form pairing centers.
2. The paring center is connected to microtubule cytoskeleton via protein bridges
(SUN and KASH proteins complex) that span the nuclear membrane.
3. Dynein (a motor protein) drives the chromosome moving around along the
nuclear membrane
4. When the two homologous chromosomes meet, pairing centers recognize each
other, then synaptonemal complex starts to form to enforce the pairing
78
https://www.youtube.com/watch?v=RMI4-C7A0sw; play first 4:30min min
79
MEIOSIS I Spindle apparatus completed.
Chromatids attached to KM.
Centrosomes Sister
with centrioles chromatids
Bivalent
Meiotic spindle
Thinking
Crossover is to
establish physical
connections between
homologous
chromosomes, thereby
??? ensuring accurate
chromosome
segregation and
producing
haploid germ cells
Prometaphase I Metaphase I
82
Independent assortment
refers to the random arrangement of pairs of chromosomes. The diagram
below shows four possible arrangements of chromosomes during metaphase 1
from an individual that has 6 total chromosomes. Suppose that the pink
chromosomes are those that the individual inherited from its mother and the blue
colored ones were inherited from its father. For each chromosome pair, the
chromosome that is on the left (maternal or paternal) is determined randomly. As
can be seen, there are several alignment possibilities.
n=3
Cleavage
furrow
Metaphase
plate Nuclear
membrane
A dyad re-forming
At the beginning of Meiosis II, each cell has After Meiosis II, each cell has
3 chromosomes Equational Division 3 chromosomes
6 chromatids 3 chromatids
6 DNA molecules 3 DNA molecules
The two cells that begin meiosis II, each have 6 chromatids that are joined as three pairs of
sister chromatids. The sorting events that occur during meiosis II are similar to those that occur
during mitosis 87
COMPARE
of meiosis I and II
the mechanisms
of chromosome
alignment (at
metaphase) and
separation (at
anaphase) in
meiotic division I
and meiotic
division II
88
Nondisjunction during meiosis I and II
89
Applications
Down syndrome
Trisomy 21 90
Numerical chromosomal
aberrations of human
91
Why is the error rate is higher in female meiosis?
Thinking
https://www.youtube.com/watch?v=4_8nmveyl1A
~1 in 2000
94
Summary: Meiosis
95
Summary: Meiosis
97
Critical thinking
/application
Infertility of mules
Mules are the result of a cross
between a horse (2n = 64) mother
http://www.horsegroomingsupplies.com/horse-
and donkey (2n = 62) father forums/attachments/horse-chat/45122-mules-
dressagemule.jpg
Liger Zonkey 98
What we did not touch/know
101