Functional Genomics
(MBG419)
Week 2 (26-27.02.2026)
‘From Genes to Genomes’
Dr Ömer Faruk Bay
Life on Earth
Planet Earth was formed from The first life appeared on Earth
The first animals evolved The first dinosaurs evolved
dust left over from the birth of 3,9 billion years ago. It was very
700 million years ago. 225 million years ago.
the sun, 4,6 billion years ago. simple, single-celled organisms
The first modern
humans evolved
300,000 years ago
Water vapour was released into the Earth’s Made by bacteria, oxygen began to The first vertebrates The dinosaurs were wiped
atmosphere through volcanism. It then cooled accumulate in the atmosphere 1,5 moved onto the land 350 out by a meteorite impact
and formed the Earth’s first oceans 4,4 billion billion years ago. million years ago. 65 million years ago.
years ago.
Life on Earth
From genes to genomics
Restriction enzymes
‘Seeds’ Pea plant experiment Werner Arber, Hamilton O. Smith & PCR
Hippocrates Gregor Mendel Daniel Nathans Kary B. Mullis 1985
(460 – 375 BCE) (1866) (1978 NP for Physiology or Medicine) (1993 NP for Chemistry)
Aristotle J. Watson & F. Crick Allan M. Maxam, Walter Gilbert The Human Genome
(384 – 322 BCE) (and by R. Franklin and. M. Wilkins) 1953 & Frederick Sanger 1977 Project
The importance of 1962 NP for Physiology or Medicine (1980 NP for Chemistry) 2003
blood in heredity. A double helix model DNA sequencing
for DNA structure
Gregor J. Mendel
1822 - 1884
• Gregor Mendel laid the foundation for
the modern understanding of inheritance
with his experiments on the transmission
of traits in garden peas. The ideas he
developed are still in use today, and his
essential insights into the physical
nature of inheritance led directly to the
understanding of the gene as a physical
entity within the cell.
Picture from Wikipedia
Experiments on peas by Mendel
• Developed “purebreeding” lines of each form.
• Performed the plant matings himself.
• In a pure-breeding line, crossing two members with
the same trait results in only offspring that are
identical to the parents for that trait.
• Crossed pure-breeding parents who had different
forms of a trait.
• All the offspring from this cross developed only tall
peas; no short peas were found.
• When these offspring were crossed among
themselves, both tall and short pea plants were
observed.
• The numerical ratio three tall-pea plants for every one
short-pea plant.
Pictures from Khanacademy
The Results of Mendel’s Garden Pea Experiment
Contrasting
Characteristic P0 Traits F1 Offspring Traits F2 Offspring Traits F2 Trait Ratios
•705 violet
Flower colour Violet vs. white 100 percent violet 3.15:1
•224 white
•651 axial
Flower position Axial vs. terminal 100 percent axial 3.14:1
•207 terminal
•787 tall
Plant height Tall vs. dwarf 100 percent tall 2.84:1
•277 dwarf
•5,474 round
Seed texture Round vs. wrinkled 100 percent round 2.96:1
•1,850 wrinkled
•6,022 yellow
Seed colour Yellow vs. green 100 percent yellow 3.01:1
•2,001 green
Inflated vs. •882 inflated
Pea pod texture 100 percent inflated 2.95:1
constricted •299 constricted
•428 green
Pea pod colour Green vs. yellow 100 percent green 2.82:1
•152 yellow
Mendel’s study
• Gregor Mendel studied inheritance of traits in pea plants. He proposed a
model where pairs of "heritable elements," or genes, specified traits.
• Genes come in different versions, or alleles. A dominant allele hides
a recessive allele and determines the organism's appearance.
• When an organism makes gametes, each gamete receives just one gene
copy, which is selected randomly. This is known as the law of segregation.
Discovery of a double helix model for DNA structure
Rosalind Franklin Maurice Wilkins James Watson and Francis Crick
Photograph 51
Watson, Crick, Wilkins & Franklin
• Double Helix Discovery: Watson, Crick, Wilkins and Franklin revealed DNA's
double helix structure.
• Base Pairing (A-T, G-C): Complementary base pairing allows DNA to replicate
accurately.
• Information Storage: The sequence of bases encodes genetic information.
• Central Dogma: DNA sequence directs the synthesis of RNA, which directs protein
synthesis.
• Mutation & Variation: Changes in the DNA sequence (mutations) lead to genetic
variation.
Discovery of restriction enzymes
Werner Arber Daniel Nathans Hamilton O. Smith
Restriction enzymes were discovered and characterized in the late 1960s and early 1970s by molecular biologists
Werner Arber, Hamilton O. Smith, and Daniel Nathans.
• The ability of the enzymes to cut DNA at precise locations enabled researchers to isolate gene-containing
fragments and recombine them with other molecules of DNA — i.e., to clone genes.
Pictures from [Link]
Discovery of DNA sequencing
Allan Maxam
Walter Gilbert Frederick Sanger
Pictures from [Link] and Wikipedia
Maxam-Gilbert and Sanger Sequencing
Maxam-Gilbert Method Sanger Method
PCR – Polymerase Chain Reaction
“Sometimes a good idea comes to you when you are not looking for it.
Through an improbable combination of coincidences, naivete and lucky
mistakes, such a revelation came to me one Friday night in April 1983, as I
gripped the steering wheel of my car and snaked along a moonlit mountain
road into northern California's redwood country. That was how I stumbled
across a process that could make unlimited numbers of copies of genes, a
process now known as the polymerase chain reaction (PCR).”
SCIENTIFIC AMERICAN April 1990
Kary B. Mullis
Prize motivation: “for his
invention of the polymerase
chain reaction (PCR)
method”
What did PCR actually do in science (mainly genomics)?
Genomic
Pre-PCR Limitations Post-PCR Advancements
Application
Rapid, efficient, and allows cloning from small DNA
Laborious, time-consuming, needed large DNA
Gene Cloning fragments, because PCR amplifies the target gene
amounts for restriction digestion/ligation.
directly.
Primarily Sanger sequencing, limited Enabled high-throughput, next-generation sequencing
DNA
throughput, required many steps, one sequence (NGS) technologies, because PCR/amplification creates
Sequencing
at a time the necessary high concentration of DNA templates.
Allows amplification of specific regions of interest from
Challenging to compare genomes across
Comparative different species for direct comparison, because primers
species, difficult to isolate comparable DNA
Genomics can be designed to target specific, conserved regions
regions.
across genomes.
Difficult to study gene expression qPCR (Quantitative PCR) enables precise measurement
Functional
patterns, techniques had low sensitivity, of gene expression levels, by allowing accurate
Genomics
complex analysis. quantification of mRNA transcripts.
PCR allows for amplification of specific genes (e.g., 16S
Difficult to study microbial
rRNA) from complex environmental samples, enabling
Metagenomics communities, isolating and culturing microbes
characterization of microbial diversity, because it
was challenging.
bypasses the need to culture individual microorganisms.
From genes to genomes
• Mendel’s Laws of Inheritance (1866) - The concept of the “gene”
- Mendel introduced the idea that traits are inherited through heritable elements (genes).
- This was the first step in understanding heredity at a fundamental level.
• Watson & Crick’s DNA Structure (1953) - The molecular basis of genes
- DNA’s double-helix model explained how genetic information is stored and passed down.
- Understanding DNA’s structure was essential for studying genes at a molecular level.
• Werner Arber & Hamilton Smith’s Restriction Enzymes (1970s) - DNA manipulation
- Restriction enzymes allowed scientists to cut DNA precisely, enabling genetic engineering.
- This was crucial for studying genes in a controlled way, marking the start of molecular genetics.
• Maxam-Gilbert & Sanger Sequencing (1977) - Reading the genetic code
- For the first time, scientists could determine the sequence of DNA.
- This shifted genetics from studying gene function to decoding the exact genetic instructions.
• Kary Mullis - Polymerase Chain Reaction (PCR) (1983) - Amplifying Genes
- PCR enabled rapid duplication of specific DNA sequences.
- It made genetic studies more accessible and allowed researchers to study genes in greater detail.
Gene
A gene is a special stretch of DNA that
that encodes for a functional product
(protein or RNA).
A gene is a unit of heredity that
determines a particular trait or
characteristic in an organism.
Prokaryotic gene Eukaryotic
structure gene structure
Introns Individual
Introns do Functionally-related interrupt the promoters
not interrupt genes occur in open reading Gene structure of regulate the
the open Gene structure of operons frame eukaryotes whose open genes
reading prokaryotes, which
frame mainly comprises the reading frame is
operon-based gene disturbed by the
clusters presence of introns
Prokaryotic genome
Bacterial Nucleoid
• The genome in prokaryotes is (mostly) contained in
single, circular DNA molecule, localised within the
nucleoid.
Kuzminov A. 2024. Bacterial nucleoid is a riddle wrapped in a
mystery inside an enigma. J Bacteriol 206:e00211-23.
Supercoiling
• Supercoiling occurs when additional turns are
introduced into the DNA double helix (positive
supercoiling) or if turns are removed (negative
supercoiling).
• Supercoiling is therefore an ideal way to package a
circular molecule into a small space. In E. coli, the
supercoiling is thought to be generated and controlled
[Link]
acids/71-dna-structure-and-replic/[Link]
by the DNA topoisomerase called DNA gyrase.
Eukaryotic genome
Chromatin
Annunziato, A. (2008) DNA Packaging: Nucleosomes and Chromatin.
Nature Education 1(1):26
Genomes in Prokaryotes and Eukaryotes
Feature Prokaryotes Eukaryotes
Location Nucleoid (cytoplasm) Nucleus
Chromosome(s) Single, circular (usually) Multiple, linear
Plasmids Often present Typically absent
Genome Size Smaller Larger
Gene Density Higher Lower
DNA Packaging NAPs, supercoiling Histones, chromatin
Introns Generally absent Typically present
Operons Common Rare
Post-Transcriptional Modification Limited Extensive
Replication Origins Single (usually) Multiple
Genome projects
H. influenzae (1995)
Genome projects
S. cerevisiae (1996)
Genome projects
E. coli (1997)
Genome projects
C. elegans (1998)
Genome projects
D. melanogaster
(2000)
Genome projects
Mouse (2002)
Genome projects
Human (2003)