DNA, Chromosomes and Genomes

DNA,CHROMOSOMES

AND GENOMES

Nanjing Foreign Language School International Centre

Tutoring Club — Biology Elite

Mike Chen

Basic Genetic Mechanisms:

Based on Molecular Biology of the Cell 6th edition

OBJECTIVE

Why DNA is so important in our lives?

How do we know that DNA is the genetic material?

What is DNA? How DNA codes for the genetic information?

What is chromosome and how does it related to DNA?

Why and how DNA is packaged inside the nucleus?

How to regulate the genetic information?

How can cells control their genetic information efficiently and flexibly?

How can cells pass on the genetic information?

How genome evolves and evolution takes place?

After this lesson, you should hopefully know…….

DNA IS THE GENETIC MATERIALEXPERIMENTAL EVIDENCE(1928)

Griffith's experiment

Griffith used two strains of

pneumococcus bacteria which

infect mice – a type III-S

(smooth, sugar coat) which

was virulent, and a type II-R

(rough) strain which was

nonvirulent.

Transforming factor

exchanging between cells

http://proteinvsdnadestroyingenzymes.blogspot.com/

EXPERIMENTAL EVIDENCE(1944)

DNA IS THE GENETIC MATERIAL

Avery–MacLeod–McCarty experiment

http://biology.kenyon.edu/courses/biol114/KH_lecture_images/How_DNA_works/FG11_02.JPG

EXPERIMENTAL EVIDENCE(1952)

DNA IS THE GENETIC MATERIAL

Hershey-Chase experiment

Hershey and Chase chose to study the

T2 bacteriophage, which infects the E.

Coli bacterium, because of its very

simple structure consisting of just:

• Protein coat

• DNA inside the coat

Viruses infect cells and transform them

into virus-producing factories:

• Viruses inject their genetic material into

cells.

• The non-genetic part of the virus

remains outside the cell.

• Infected cells produce large numbers of

the virus

• The cell bursts releasing the copied

virus

©The McGraw-Hill Companies, Inc. Permission granted for reproduction

STRUCTURE AND FUNCTION OF DNA

A deoxyribonucleic acid (DNA) molecule

consists of two long polynucleotide

chains composed of four types of

nucleotide subunits.

Each subunit is composed of:

• phosphate group

• deoxyribose

• nitrogen base (Adenine, Thymine,

Cytosine, Guanine)

Main feature:

• sugar-phosphate backbone

• helix structure

• anti-parallel

• hydrogen bonding

• base pairing

• Two ends: 5’ and 3’ end


http://cbm.msoe.edu/markMyweb/Hydrogen%20Bo

nding%20Tutorial_MARK.html

Base pairing in DNA

• purines: adenine and guanine (heavier and longer,

two rings)

• pyrimidines: thyme and cytosine (lighter and

shorter, one ring)

• each base pairing is in similar width, holding the

sugar backbones a constant distance

• two hydrogen bonds forming between A and T

• three hydrogen bonds forming between C and G

http://cbm.msoe.edu/markMyweb/Hydrogen Bonding Tutorial_MARK.html


Molecular biology of the cell 6/e ©Garland Science(2015)

10.4 nucleotide pairs per turn

0.34nm between each nucleotide pair

major/miner groove in double helix

CHROMOSOMAL DNA AND ITS PACKAGING

Packaging of DNA:• prevent form unmanageable tangle of DNA

• remain accessible for some section of DNA

• Chromosomes: a single, enormously long linear DNA molecule along with the proteins that fold

and pack the one DNA thread into a more compact structure

• Each human cell (except gametes) contains two copies of each chromosome, one from mother

and one form father, called “homologous chromosomes (homologs)”

• Non-homologous chromosome pairs are sex chromosomes (Y-father, X-mother, XY-male, XX-

female)

• each human cell contains 46 chromosomes, 22 pairs of homologs and 1 pair of sex

chromosome

http://www.iitk.ac.in/infocell/Archive/dirnov3/science.htmlhttp://geneed.nlm.nih.gov/topic_subtopic.php?tid=15&sid=17

http://www.iitk.ac.in/infocell/Archive/dirnov3/science.html

http://geneed.nlm.nih.gov/topic_subtopic.php?tid=15&sid=17


Distinguish of chromosomes

• DNA hybridisation (colour painting using fluorescent dyes); stain them with dyes (showing patterns

of bands)

• display of the 46 chromosomes at mitosis is called human karyotype

• abnormalities of chromosome can be detected by banding patterns or chromosome painting

http://www.iaszoology.com/chromosome-painting/


Specialised nucleotide sequences

• Replication origins: the location where the duplication of DNA begins

• Centromere: allow one copy of each duplicated and condensed chromosome to be pulled into

each daughter cells when a cell divide. Kinetochore (protein complex) forms at the centromere,

making the chromosomes apart

• Telomeres: the end of the chromosomes, protect the end of chromosomes from being mistaken

by the cell for a broken DNA molecule in need of repair

• Each chromosome has multiple origins of replication, one centromere and two telomere

https://www.boundless.com/biology/textbooks/boundless-biology-textbook/cell-

reproduction-10/the-cell-cycle-88/the-mitotic-phase-and-the-g0-phase-396-11622/http://www.yourgenome.org/facts/what-is-a-telomere https://wikispaces.psu.edu/display/230/DNA+and+Chromosomes

http://www.yourgenome.org/facts/what-is-a-telomere

https://wikispaces.psu.edu/display/230/DNA+and+Chromosomes


• Gene: a segment of DNA that contains the instructions for making a particular protein

• Genes are located between the centromeric and telomeric regions along the entire

chromosome

• A single chromosome usually has a few hundred to several thousand genes

• In lower eukaryotes (such as yeast)

• Genes are relatively small

They contain primarily the sequences encoding the polypeptides

Very few introns are present

• In higher eukaryotes (such as mammals)

• Genes are long

They tend to have many introns

Intron lengths from less than 100 to more than 10,000 bp

If stretched end to end, a doploid set of human chromosomes will be over 2 meter long. Yet the

cell’s nucleus is only 2 to 4 μm in diameter. Therefore, the DNA must be tightly compacted to fit

Brooker, Robert J. "Genetics: Analysis and Principles." Lecture.

HISTONE AND NUCLEOSOME


Chromatin: complex of both classes of protein

(histone & non-histone chromosomal protein) with

the nuclear DNA of eukaryotic cells

Nucleosome: a protein-DNA complex, with two

molecules each of histone H2A, H2B, H3 and H4,

and double stranded DNA that is 147 pairs long.

http://schoolworkhelper.net/dna-structure-and-function/



A histone octamer is the eight protein complex found at the center of a nucleosome core particle.

It consists of two copies of each of the four core histone proteins (H2A, H2B, H3 and H4).

Linker DNA between each nucleosome core can vary in length from a few pairs up to 80

On average, nucleosome repeats at intervals of about 200 nucleotides

https://www.mun.ca/biology/scarr/Histone_Protein_Structure.html

https://www.mun.ca/biology/scarr/Histone_Protein_Structure.html



All four histone protein are small (102-135 amino acids), and have the same structural motif called

histone fold, formed from three alpha helices connected by two loops

http://www.intechopen.com/source/html/43165/media/image1.png


http://humgenomics.biomedcentral.com/articles/10.1186/1479-7364-6-10

http://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(98)01201-8

N-tail is subjected to several

forms of covalent modification

http://www.intechopen.com/source/html/43165/media/image1.png

http://humgenomics.biomedcentral.com/articles/10.1186/1479-7364-6-10

http://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(98)01201-8



H2A and H2B form a dimer through an interaction called handshake and H3 and H4 forms a dimer

through the same type of interaction

Two H3-H4 dimer then further combines to form a tetramer.

An H3-H4 tetramer then combines with two H2A-H2B dimer to form the histone octamer core

where DNA is wound.

142 hydrogen bonds are formed between the histone core and the DNA, along with numerous

hydrophobic interactions and salt linkages.

Das, Chandrima, Jessica K. Tyler, and Mair E.a. Churchill. "The Histone Shuffle: Histone Chaperones in an Energetic Dance."

Trends in Biochemical Sciences 35.9 (2010): 476-89. Web.




Packed of nucleosome: Histone tails and histone H1 proteins

Histone H1 protein presents 1-to-1 ratio with nucleosome cores, and it contacts both the DNA and

nucleosome core. H1 proteins change the path of the DNA as it exits from the nucleosome.




ATP-Dependent Chromatin remodelling complexes: the arrangement of the nucleosomes on

DNA can be highly dynamic, changing rapidly according to cells’ need.

By using the energy from ATP hydrolysis, the complexes can reposition nucleosome cores,

remove either all or part of the nucleosome core, make less DNA winding looser

Nucleosome has a dynamic structure, it will unwrap from each end and recloses thus leaving 10

to 50 milliseconds of free DNA for protein to bind in.


CHROMATIN STRUCTURE AND FUNCTION

• Heterochromatin: compact chromatin region that share the common feature of being unusually

resistant to gene expression

• Euchromatin: less condense region of chromatin

• Position effect: euchromatin translocated into the neighbourhood of heterochromatin, which

always causes silencing, inactivation of genes.

• Position effect variegation: once the heterochromatic condition is establish on a piece of

chromatin, it tends to be stably inherited by all of that cell’s progeny

http://www.stomponstep1.com/epigenetics-prader-

willi-sydrome-angelman-syndrome/

http://www.discoveryandinnovation.com/BIOL202/notes/lecture18.html

http://www.discoveryandinnovation.com/BIOL202/notes/lecture18.html


Covalently modified of core histones:• acetylation of lysines, the mono-, di-, and trimethylation of lysins and the phosphorylation of

serines.

• most of the modification occur on N-terminals of histone tails

• Specific enzymes are responsible for the modification: histone acetyl transferases (HATs) are

responsible for adding of acetyl group and histone deactylase complexes (HDACs) are for

removing acetyl group

• Acetylation of lysine on the N-terminal tails loosens chromatin structure

• Methylation of lysine on the N-terminal tails tightens chromatin structure

• Histone modification can also recruit proteins: trimethylation of one specific lysine on the histone

H3 tail attracts the heterochromatin-specific protein HP1 and contributes to the establishment

and spread of heterochromatin

Rodriguez-Paredes, and Esteller. Schematic Representation of Histone Modifications. Digital image. Nature, 2011. Web.


Variants of histone proteins• those proteins are synthesised and instead into a already formed chromatin, which requires a

histone-exchange process catalysed by the ATP-dependent chromatin remodelling complexes.

CHROMATIN STRUCTURE AND FUNCTIONCovalent modification and histone variants in controlling chromosome functions• The writer is a enzyme that create a specific modification on one or more of the four

nucleosomal histone

• The writer collaborated with a reader protein to spread its mark from nucleosome to

nucleosome by means of the reader-writer complex

• A similar process is used to remove the histone modification. An eraser protein is recruited

to the complex


CHROMATIN STRUCTURE AND FUNCTIONCertain DNA sequences mark the boundaries of chromatin domains and separate one such

domain from another. The sequence is called barrier sequenceIn the case of cells which are destined to give a rise in red-blood cells, a sequence called HS4

normally separate the active chromatin (euchromatin) that contains beta-globin genes. Barrier

sequence in this case contains a cluster of binding sites for histone acetylase enzyme. Acetylation

and methylation of the lysine side chain cannot be performed together and the methylation are

required for the spread of heterochromatin.

This mechanism stops the spread of reader-writer complex and separate the neighbouring

chromatin

http://www.gla.ac.uk/researchinstitutes/cancersciences/research/units/epigenetics/adamwest/research/


The chromatin in the centromere contains a centromere-specific variant H3 histone, known as

CENP-A (centromere protein-A)

In human particularly, centromere also consists of short, repeated DNA sequence called alpha

satellite DNA sequences, but this sequence can be also found in other part of the chromosome,

which indicated they are not sufficient for formation of centromere

In some cases, newly formed human centromere called neocentromere cane formed without

alpha satellite DNA sequence

Centromeres in complex organism are defined by an assembly of proteins, rather than by specific

DNA sequence.

http://www.nature.com/ncb/journal/v15/n9/full/ncb2833.html

http://www.nature.com/ncb/journal/v15/n9/full/ncb2833.html


Cooperative recruitment of proteins, along with the action of reader-writer complexes, can not only

account for the spreading of specific from of chromatin in space along the chromosome, but also

for its propagation across cell generation.


THE GLOBAL STRUCTURE OF CHROMOSOME

Chromosome are folded into large loops of chromatin

Polytene chromosomes are over-sized chromosomes which have developed from standard

chromosomes and are commonly found in the salivary glands of Drosophila melanogaster.

Polytene chromosome are viewed under light microscope with dark bands and light interbands.

DNA are more condensed in the dark park and may also contain high concentration of proteins.

http://modencode.sciencemag.org/drosophila/introduction

http://modencode.sciencemag.org/drosophila/introduction


Specific set of non-histone proteins assemble on these nucleosomes to affect biological function

in different ways

Interphase chromosome can be considered as a chromatin structure containing particular

nucleosome modification associated with a particular set of non-histone proteins.

Classical heterochromatin contains more than six such proteins, including heterochromatin protein

1 (HP1)

Chromatin loops decondense when the genes within them are expressed




Wheeler, Richard. Chromatin Structures. Digital image. Wikipedia. 2005. Web.

HOW GENOMES EVOLVE

Homologous genes: genes that are similar in both their nucleotide sequence and fiction because

of a common ancestry

Conserved sequences are similar or identical sequences that occur within nucleic acid

sequences, protein sequences, protein structures or polymeric carbohydrates across species or

within different molecules produced by the same organism.

Shafee, Thomas. Histone Alignment. Digital image. Wikipedia. 8 Dec. 2014. Web.

Non-conserved regions will reflect DNA whose sequence is much less likely to be critical for

function

The only regions that will have remained closely similar in the two genomes are those in which

mutations would have impaired function and put the animals carrying them at a disadvantage,

resulting in their elimination from the population by natural selection.

This region is called conserved region

Evolution depends on accidents and mistakes followed by nonrandom survival.

HOW GENOMES EVOLVE

Errors in DNA replication, DNA recombination, or DNA repair can lead either to simple local

changes in DNA sequence—so-called point mutations such as the substitution of one base pair

for another—or to large-scale genome rearrangements such as deletions, duplications, inversions,

and translocations of DNA from one chromosome to another.

Small blocks of DNA sequence are being deleted from and added to genomes at a surprisingly

rapid rate. Thus, if we assume that our common ancestor had a genome of human size (about 3.2

billion nucleotide pairs), mice would have lost a total of about 45% of that genome from

accumulated deletions during the past 80 million years, while humans would have lost about 25%.

However, substantial sequence gains from many small chromosome duplications and from the

multiplication of transposons have compensated for these deletions.

Veryhuman. Evolution-Of-Duplicate-Genes. Digital image. Wikipedia. 2012. Web.

THE END