L19: Mitosis and Meiosis

What is genetics?

• The basis of inheritance

• The mechanism of evolution

• A methodology for experimental biology

• Essential tool for all biological and medical scientists

What is genetics the study of?

inheritance and variation

What is inheritance

How “traits” are inherited and passed down from one generation to another

What is pharmacokinetics?

personalised medicine (already in place for some chemotherapy drugs)

Somatic cells

Any body cell whcih does not produce gametes

Germ cells

Diploid reproductive cell that gives rise to a gamete

Diploid cells

Have 2 sets of chromosomes (2 copies of the basic genetic complement for that organism)

Haploid cells

Have one set of chromosomes (1 copy of the basic genetic complement for that organism)

what do children inherit from their parents

genes

Why is DNA folded up

It has to be unwound and replicated/transcribed & translated when needed. There has to be order to this so DNA is not damaged during the process.

Length of DNA in nucleus of a human sperm cell

~ 1m

Role of histones

Proteins which help with the folding of DNA (DNA is wrapped around them then looped an coiled)

What does methylation do

Affect how lightly coiled the DNA is and effectively switches genes off

What are phenotypes created from

complex interactions of genes

How is variation demonstrated

by the differences in appearance that offspring show from their siblings and parents

What are genes and what are they made up of

The units of heredity that are made up of segments of DNA

Where are genes located

A locus (number or place of where it exists) of a particular chromosome in the nucleus

How are genes passed on to the next generation

via reproductive cells called gametes

How many base pairs are in the human genome and what is the length of each base pair?

• 3×10⁹ base pairs

• 0.34nm each

where does DNA get replicated and transcribed

At the correct place at the correct time

what is DNA divided into

discrete lengths called chromosomes

Number of chromosomes in different species

• Humans: 23

• Cat: 19

• Fruit fly: 4

• Potato: 24

• Horse: 32

• Donkey: 31

the 2 types of cell division

• Mitosis: normal cell life cycle

• Meiosis: for reproduction

What are cells doing for the majority of their life cycle

Producing proteins & growing for DNA replication

Where do the spindle fibres originate from

Centrioles

What is the purpose of mitosis

Occurring all the time and replacing damaged or removed cells

What are the sex chromosomes of males and females

• Females XX

• Males XY (the Y is an incomplete X)

How are new males and females made at fertilisation in terms of X and Y

At fertilisation, the new individual inherits an X chromosome from the mother and either an X or Y from the father:

• X and Y makes a new male

• X and X makes a new female

What are autosomes

the 22 pairs of chromosomes that do not determine sex

What are the 2 chromosomes in each pair called

Homologous chromosomes (homologs)

Features about chromosomes in a homologous pair

same length and carry the alleles of the same genes

What is the human karyotype

An ordered display of the pairs of chromosomes in a cell

what is a karyotype

• a picture of the homologous chromosomes of an organism.

• It can be used to identify anomolies of several megabases (deletions, inversions, duplications)

• cells are arrested in metaphase and treated with colchicine which poisons microtubules

• Chromosomes organised according to size and organisation of their centromeres

Non-homologous chromosomes

carry different genes

In human cells, what does each pair of homologous chromosomes have

one chromosome from each parent

How many chromosomes in total in a somatic cell

46

• 2 sets of 23 (one from mother and one from father)

When does mitosis occur?

Before cytokinesis, after G₂ in the cell cycle

where does mitosis occur

In many tissues that have to replace cells e.g. blood, the epithelium of the small intestine

Why does Mitosis happen

To produce new cells which contain a diploid set of chromosomes, replacing others which have died or been removed

What is Meiosis

Cell division producing gametes which each posses the haploid number of chromosomes (n) and haploid DNA content (c)

• when DNA is replicated, reductional division occurs so the number of chromosomes is reduced

Why is Meiosis necessary?

To allow offspring to be produced with half of their genetic information from their mother and half from their father

When does Meiosis occur

After S-phase in the cell cycle when the DNA has been replicated

How do cells begin and finish meiosis

• Begin with 2n (2x diploid number of chromosomes) and 4c (4x haploid content of DNA)

• End product is 4 daughter cells with haploid number of chromosomes and haploid content of DNA

How many sets of cell divisions in meiosis

2 : Meiosis I and II resulting in 4 daughter cells with ½ of the number of chromosomes as the parent cell

What is synapsis in meiosis ?

• Occurs during prophase 1

• Homologous chromosomes pair up and closely align with each other forming a tetrad (2 homologous chromosome with 2 sister chromatids)

Meiosis I

Homologous chromosomes separate forming 2 haploid daughter cells (reductional division)

Meiosis II

Sister chromatids separate forming 4 haploid daughter cells with a haploid set of unreplicated chromosomes

What does mitosis conserve

the number of chromosome sets, producing cells that are genetically identical to the parent cell

What does Meiosis reduce

The number of chromosome sets from 2 (diploid) to 1 (haploid), producing cells genetically different from the parent and from eachother

The 3 unique events occurring in Meiosis I

1. Tetrads (paired homologous chromosomes) are found at the metaphase plate instead of individual replicated chromosomes.

2. Instead of sister chromatids, hmologous chromosomes separate

3. Synapsis & Crossing Over: Homologous chromosomes physically connect and exchange genetic information

When do chiasma form

As homologous chromosomes closely interact with eachother

What do chiasma allow?

DNA exchange between non-sister chromatids.

How do mutations contribute to genetic variation?

• Mutations are an original source of genetic diversity which create different versions of alleles

• Genetic variation is produced via the reshuffling of alleles during meiosis and reproduction

How does independent assortment of chromosomes contribute to genetic variation

there is an equal chance of chromosomes from each parent lining up at metaphase I

How does Crossing over result in genetic variation

Results in recombinant chromosomes that contain genes from each parent

How does random fertilisation contribute to genetic variation

Any egg with any sperm

What is Independent Assortment of chromosomes- Meiosis

Where homologous pairs of chromosomes orientate randomly at metaphase I of meiosis. Each pair of chromosomes sorts maternal and paternal homologues into daughter cells independently of the other pairs

The number of combinations possible when chromosomes assort independently into gametes

2ⁿ (n=the haploid number)

• in humans n=23 so there are over 8.4 million possible combinations of chromosomes

What does crossing over in meiosis produce?

Recombinant chromosomes which combine genes inherited from each parent

When does crossing over being in Meiosis?

very early in prophase I as homologous chromosomes pair up gene by gene

What do zygotes have

• any from 70 trillion diploid combinations

• A very unique genetic identity

What does genetic variation drive and how?

Evolution

• Reshuffling of alleles produces genetic variation

• Further variation when each homologous pair can line up independently during Metaphase I : Independent assortment

• More variation via crossing over of sister chromatids and breaking and re joining at the crossover point of the chiasma

• Natural selection results in accumulation of genetic variations favoured by the environment

What happens as an organism grows and develops

Chemical reactions activate and deactivate parts of the chemical modification of specific genes or gene-associated proteins of an organism

What is epigenetics?

The study of the chemical modification of specific genes or the gene-associated proteins of an organism. Epigenetic tags include methylation which influences the level of transcription that can occur of particular genes. These tags are faithfully reproduced as cells grow and divide

Stages of the Cell Cycle

1. Interphase: Preparation (90% of cycle)

2. M phase: Division/Mitotic Phase

Stages of interphase

Very active period of growth and metabolism, the longest phase of the cell cycle where the cell grows, carries out normal functions and prepares for division.

1. G1 phase: First Growth stage where the cell grows in size, new proteins are made, organelles are copied and cell prepares for replication (S)

2. S phase: DNA replication, duplicating each chromosome

3. G2 Phase: Second Growth stage where the cell grows further, makes more new proteins and prepares for mitosis

Where are kinetochore proteins?

At the centromere - about 100 of them ensure microtubules bind to the correct place on the centromere

M phase of the cell cycle

Mitotic phase where the cell divides into 2 daughter cells. It is split into:

1. Mitosis (Nuclear division): Prophase, Metaphase, Anaphase, Telophase

2. Cytokinesis (cytoplasm division/ cell splitting)

Prophase

• Chromosomes condense into visible chromosomes

• Microtubules disassemble and reassemble to form spindle fibres and asters by polymerisation

• Some spindle fibres attach to kinetochore and tension sensitive proteins make sure each chromatid is attached to a centrosome

Prometaphase

The nuclear membrane dissolves & chromosomes begin to align

Metaphase

Chromosomes move and line up along metaphase plate on the equator (this is due to polymerisation and depolymerisation of microtubules in spindle fibres). Spindle fibres attach to centromeres of chromosomes.

Anaphase

• Rapid

• 2 sister chromatids are pulled apart to opposite sides of the poles by depolymerisation of kinetochore proteins

• They are now called chromosome sin their own right

Telophase

• Separated chromosomes are pulled by spindle fibres to opposite poles of the cell

• The cell briefly had 2 daughter nuclei

• Chromosomes uncoil, decondense back to chromatin and 2 nuclear membranes made

Cytokinesis

• Cytoplasm divides

• 2 daughter cells formed

What is essential for mitosis to being

DNA replication must be complete and all chromosomes must be attached to the spindle before pulling apart

What signals the end of G2 and the start of Mitosis/Meiosis

Maturation Promoting Factor

What can epigenetics explain

• Nature vs nurture

• Could affect the placebo effect

• How diseases develop

• Personalised medicine

Somatic vs Germ cells

• Somatic: The body cells which make up most of an organism’s tissues and organs. They are diploid. Do not participate in sexual reproduction and divide by mitosis to ensure new cells have the same number of chromosomes as the original

• Germline: Reproductive cells (sperm, egg, pollen and ovules). They are haploid. They are produced via meiosis which reduces the chromosome number by half, allowing genetic diversity when they combine during fertilisation.

Haploid definition

A haploid cell has one set of chromosomes which means it only contains one copy of each chromosome

e.g. gametes in humans are haploid with 23 chromosomes each

diploid definition

• 2 sets of chromosomes (2n)- one from each parent

• paired chromosomes (one maternal and one paternal)

• e.g. somatic body cell in humans are diploid with 46 chromosomes

Homologous chromosomes meaning

• chromosome pairs which have the same genes in the same order but may carry different versions (alleles) of those genes

• one chromosome in each pair comes from the mother and one from the father

• e.g. humans have 23 pairs of homologous chromosomes (except males who have XY sex chromosomes)

Non-homologous chromosomes

• chromosomes that do not match because they contain different sets of genes

• e.g. Chromosome 1 and 5 in humans are non homologous as they carry different genes

• e.g. X and Y in males are not fully homologous

DNA

• The fundamental molecule which carries genetic information

• double-helix

• tightly packaged around proteins (histones) to fit inside nucleus

Chromatin

• In a normal, non-dividing cell, DNA exists as chromatin which is a loose thread-like complex of DNA and Proteins

• Allows for gene expression and DNA replication

What is a chromosome

• when a cell prepares to divide, chromatin condenses into chromosomes

• they are highly condensed, coiled structures of DNA and proteins

• each one contains a single long DNA molecule which has many genes

Chromatids

• Before cell division, DNA replication forms 2 identical copies of a chromosome

• these copies are called sister chromatids and are attached at a region called the centromere

• once the sister chromatids separate during cell division, they are then individual chromosomes

what are epigenetic influences

heritable changes in gene expression which do not involve changes in the DNA sequence and are influenced by chemical modifications to DNA, affecting how genes are switched on or off

epigenetic influences in mitosis

• regulate which genes are active/inactive in different cell types

• causes DNA methylation which can silence genes which should not be active in a specific cell type

• can loosen DNA, making genes more accessible for transcription

• abnormal modifications can lead to uncontrolled cell division and lead to cancer

Epigenetic influences in meiosis

• some genes can be epigenetically marked so only one copy from one parent is active

• meiotic errors such as nondisjunction can occur due to faulty epigenetic regulation

what happens to the chromosomes and alleles during Prophase

• chromatin condenses into visible chromosomes

• chromosomes consist of 2 sister chromatids joined at a centromere

• homologous chromosomes not paired together

• each chromatid contains the same alleles as its sister chromatid

Chromosomes and alleles during metaphase

• chromosomes: align at the metaphase plate and spindle fibres from opposite poles attach to each chromatid at the centromere

• alleles: each chromatid carries the same alleles and their separation will ensure that each daughter cells gets and identical genetic copy

Chromosomes and alleles during anaphase

• chromosomes: sister chromatids separate as spindle fibres pull them to opposite poles of the cell. once separated, each chromatid is now considered an individual chromosome

• Alleles: alleles on each chromatid are separated equally, ensuring that each new cell will receive one complete set of alleles identical to the parent cell

Chromosomes and alleles during telophase

• chromosomes: decondense back into chromatin and the nuclear envelope re-forms around each set of chromosomes

• alleles; each nucleus now contains the same set of alleles as the original parent cell, maintaining genetic consistency

Describe Meiosis I (Prophase I)

• Chromatin condense into visible chromosmes which each consist of 2 sister chromatids joined at centromere. Homologous chromosomes pair up to form tetrads and crossing over occurs between non-sister chromatids at the chiasmata to exchange genetic material

• The crossing over shuffles alleles and creates new allele combinations

Describe meiosis I (Metaphase I)

• tetrads allign at metaphase plate

• spindle fibres attach to the centromeres of homologous chromosomes

• independent assortment occurs where homologous chromosome pairs randomly orient at the metaphase plate

Meiosis I (Anaphase I)

• Homologous chromosomes separate and move to opposite poles while sister chromatids remain attached at their centromeres

• Random separation of homologs ensures different combinations of alleles in daughter cells

Meiosis I (Telophase I)

• each new nucleus receives one set of chromosomes

• each daughter cell has a random mix of parental and maternal alleles due to independent assortment

• 2 haploid cells with chromosomes still in duplicated form

Meiosis II (Prophase II)

• chromosomes re condense if they had decondensed in telophase I

Meiosis II (Metaphase II)

• chromosomes allign at metaphase plate and spindle fibres attach to both sides of the centromere

Meiosis II (Anaphase II)

• centromeres divide, and sister chromatids pulled apart to opposite poles to become individual chromosomes

• each gamete gets one chromatod which may carry a recombinant allele combination from earlier crossing over