A Microscopic to Molecular Perspective in Modeling

Chromosomes

Educators attending this workshop will:o Support the NGSS student learning outcomes of three dimensional lesson design

utilizing the:

o Connecting Nucleotides to Chromosomes Kit© to:o Construct acrocentric, metacentric and submetacentric chromosomeso Create and analyze karyogramso Model and explain the process of mitosiso Model and explain the process of meiosis at the microscopic and molecular scaleo Explain genetic variation through modeling

o Learn something new and interesting that is for your own professional development.

o HAVE FUN!

WORKSHOP LEARNING OBJECTIVES

WORKSHOP LEARNING OBJECTIVES

What NGSS dimensions will be targeted?

SEPs CCCs DCIsAsking Questions and

Defining Problems Patterns LS1.A: Structure and Function

Developing and Using

Models

Cause and Effect:

Mechanism and Explanation

LS1.B: Growth and

Development of OrganismsConstructing Explanations

and Designing Solutions

Scale, Proportion, and

QuantityLS3.A: Inheritance of Traits

Engaging in Argument

from EvidenceStructure and Function

LS3.B: Variation in Traits

Analyzing and

Interpreting DataStability and Change

HOW DO WE KNOW WHAT WE KNOW?

Karl Wilhelm von Nägeli noted “transitory cytoblasts” while studying pollen formation in 1842. We now call these observed structures chromosomes!

Part of a long and complicated history!

Unfortunately, Nägeli made a name for himself by rejecting Gregor Mendel’s studies on inheritance and instead tenaciously holding on to his ideas of spontaneous generation and orthogenesis.

https://en.wikipedia.org/wiki/Carl_N%C3%A4geli

Image taken from The Cell-theory: a Restatement, History, and Critique Part V. The Multiplication of Nuclei By JOHN R. BAKER (From the Cytological Laboratory, Dept. of Zoology, University Museum, Ox

HOW DO WE KNOW WHAT WE KNOW?

https://www.uni-kiel.de/grosse-forscher/index.php?nid=flemming&lang=e

Walther Flemming is generally credited with describing the behavior of chromosomes during mitosis in 1882.

https://www.nature.com/scitable/content/drawing-of-mitosis-by-walther-flemming-43904

History continued . . . .

Consider this . . .An accurate count of human chromosomes didn’t occur until 1956by Tjio and Levan!

Flemming gets special mention because he had the heart of a teacher!

MULTIPLE MODELS OF CHROMOSOMES

ANOTHER CHROMOSOME MODEL!?!

YES!Why you ask?All shall be revealed in due time!

Now let’s build some chromosomes!Centromere

Linker

Telomere

Linker

Telomere

p arm

q arm

BUILD MODEL CHROMOSOMES

Acrocentric SubmetacentricMetacentric

BUILD MODEL CHROMOSOMES

Replicate your chromosomes!Build a maternal and paternal set!

BUILDING MODEL CHROMOSOMES

Completed Maternal and Paternal Chromosomes!

n = 3 (haploid number of chromosomes)

2n = 6 (diploid number of chromosomes)

MODEL KARYOGRAMS TO DETERMINE KARYOTYPE

http://ib.bioninja.com.au/standard-level/topic-3-genetics/32-chromosomes/karyograms.html http://ib.bioninja.com.au/standard-level/topic-3-genetics/32-chromosomes/karyograms.html

WHAT EXACTLY IS A CHROMOSOME?

http://ib.bioninja.com.au/standard-level/topic-3-genetics/32-chromosomes/karyograms.html

https://qph.fs.quoracdn.net/main-qimg-a5c27f2ff2b2ba120f64285d92a2f408-c

Chromosome? Duplicated Chromosome? Chromatid? Chromatin? Centromere?

BUT where’s the DNA?

PUT ON YOUR MOLECULAR SPECTACLES!

Replicated Chromosome at the Nucleotide Level!

What can this model do to expand the concept of the chromosome?

MODELING MITOSIS TO ANSWER AN ESSENTIAL QUESTION

How are characteristics passed from one generation of cells to the next?

Cell division for growth and repair of somatic (body) cells

Mitosis

Genetic information is maintained!

How does the model allow me to see that the genetic information is maintained?

AND SPEAKING OF INHERITANCE. . .

Why do we all look different?

http://pozboysg.tumblr.com/post/28550047424/janices-story-my-life-with-a-hiv-family-member

http://statchatva.org/2013/10/16/multigenerational-households/

https://www.ecald.com/updates/indian-and-south-asian-families-support-caring-for-their-disabledspecial-needs-family-members-monthly-support-group-meeting-28th-july-2016/

http://lovefromthedesert.blogspot.com/2010/10/redhouse-family.html

https://altright.com/2018/01/24/race-is-just-your-extended-family/https://nypost.com/2015/03/02/meet-the-bi-racial-twins-no-one-believes-are-sisters/

GENERATING GENETIC VARIATION DURING MEIOSIS

If the chromosomes line up like this . . . . . . you get gametes like this.

If the chromosomes line up like this . . . . . . you get gametes like this.

GENERATING GENETIC VARIATION DURING MEIOSIS

If the chromosomes line up like this . . . . . . you get gametes like this.

GENERATING GENETIC VARIATION DURING MEIOSIS

If the chromosomes line up like this . . . . . . you get gametes like this.

GENERATING GENETIC VARIATION DURING MEIOSIS

Due to independent assortment of chromosomes, in a cell where the haploid number of chromosomes equals 3 or 2n = 6, the number of different chromosomal arrangements in the daughter cells is 8!

GENERATING GENETIC VARIATION DURING MEIOSIS

The number of possible combinations when chromosomes sort independently during meiosis is 2n, where n is the haploid number of chromosomes in the organism.

In humans, the number of possible combinations of maternal and paternal chromosomes in the resulting sex cells is 223, or approximately 8.4 million!

WOW! That’s a lot of variation WITHOUT any crossing over!

GENERATING GENETIC VARIATION DURING MEIOSIS

PUT ON YOUR MOLECULAR SPECTACLES!

DNA Replication!

PUT ON YOUR MOLECULAR SPECTACLES!

Now let’s talk about inheritance!

PUT ON YOUR MOLECULAR SPECTACLES!

Now you can connect the Punnett Square to a nucleotide sequence!

https://edu.glogster.com/glog/sickle-cell-anemia/2bbb3vtjfok

Why the one gray nucleotide?

PUT ON YOUR MOLECULAR SPECTACLES!

Now Connect the Nucleotide Sequence to Protein Structure!

GENERATING EVEN MOREGENETIC VARIATION

CROSSING OVER

❖ The “swapping” of chromosome parts between homologous chromosomes

❖ Typically shown between two adjacent sister chromatids

https://qph.fs.quoracdn.net/main-qimg-a5c27f2ff2b2ba120f64285d92a2f408-c

GENERATING EVEN MOREGENETIC VARIATION

CROSSING OVER

Can the “outside” chromatids cross over?

They can indeed! Alignment of chromosomes happens in 3 dimensional space.

https://qph.fs.quoracdn.net/main-qimg-a5c27f2ff2b2ba120f64285d92a2f408-c

OR

Modeling “Traditional” Microscopic Meiosis Crossing Over

Homologous chromosomes line up.

Chromatids exchange parts.

Sister chromatids cross over.

GENERATING EVEN MOREGENETIC VARIATION

MOLECULAR CROSSING OVER

Homologous chromosomes align.

Consider “molecular meiosis”.

Begins with a BOLD step.

A specialized protein makes a double stranded break in one chromosome.

MOLECULAR CROSSING OVER

5’ to 3’ nuclease digests one strand from each end of the cut, one nucleotide at a time.

MOLECULAR CROSSING OVER

Homologous DNA sequence is “unzipped”.

MOLECULAR CROSSING OVER

Strand invasion occurs.

MOLECULAR CROSSING OVER

DNA polymerase uses homologous chromosome as the template to fill in the gaps (note gray nucleotides).

MOLECULAR CROSSING OVER

Single-stranded cuts in the chromosome that was used as the template (the red chromosome).

MOLECULAR CROSSING OVER

Ligase joins breaks in the DNA to form two recombinant chromosomes.

MOLECULAR CROSSING OVER

MODELING CROSSING OVER

Microscopic Crossing Over Molecular Crossing Over

According to the 4th edition of Molecular Biology of the Cell, on average, between two and three crossover events occur on each pair of human chromosomes during meiotic division I.

Think of the additional variation generated with crossing over!

MODELING CHROMOSOMAL ABERRATIONS

For example: TranslocationMicroscopic Scale Molecular Scale

MODELING OTHER CHROMOSOMAL ABERRATIONS

Students can think with models to show additional aberrations like . . .

Microscopically AND Molecularly

MODELING NONDISJUNCTION

When NONDISJUNCTION occurs during Meiosis I . . .

OOPS!

RESULT?No gametes with the correct number of chromosomes!

n - 1

n + 1

MODELING NONDISJUNCTION

When NONDISJUNCTION occurs during Meiosis II . . .RESULT?Some gametes have the correct number of chromosomes and some do NOT!

OOPS!

n + 1n n - 1

With their molecular spectacles firmly in place. . .

Guide students to think with models:

DIVING DEEPER WITH MODELS

How do chromosomes “find” their homologs during meiosis?

https://opentextbc.ca/biology/chapter/6-1-the-genome/

The bouquet arrangement in hexaploid wheat.

Carrie R. Cowan et al. Plant Physiol. 2001;125:532-538 ©2001 by American Society of Plant Biologists

❖ Telomeres are the same ❖ Why?

❖ Bouquet❖ Begin pairing at ends

HOW DO CHROMOSOMES FIND THEIR HOMOLOGS?

Two separate mitotic spindles

JUST WHEN YOU THOUGHT YOU UNDERSTOOD CELL DIVISION . . .

Reichmann et al., Science 361, 189–193 (2018) 13 July 2018

A New Way to Think About First Mitosis

Zielinska et al., Science 361, 128-129 (2018) 13 July 2018

THANK YOU!

HOW CAN I GET THESE GREAT MODELS?

Coming SOON this Fall

PURCHASE from 3D Molecular Designs:

https://www.3dmoleculardesigns.com/Education-Products.htm

Be sure to use your 20% show special discount code: STEM19

BORROW from the Model Lending Library:

http://cbm.msoe.edu/lendingLibrary/index.php

THANK YOU!

For more molecular stories. . .

Come visit us at booth 501!

We hope to see you soon!