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LSM2107 Evolutional Biology

Lecture 4: How do variations come about?

A/P Li Daiqin
S2-01-03
daiqin.li@nus.edu.sg
Lecture was prepared using
the resource below

Chapter 6 of textbook

Also uploaded into

Canvas
Where did all this diversity come from?
The sources of
genetic variations
• Mendelian genetics
• Transmission genetics
• Variation and mutation
• Mutation rates and
fitness consequences
Key questions related
to genetic variations
• How does an understanding of DNA,
amino acids, and proteins help us
understand the evolution of life?

• What is transmission genetics, and

how does our understanding of this
topic the way that we study the
processes of evolution?

• How does mutation generate genetic

variation, and how do mutations
affect the evolutionary process?
Key terms
• Transmission genetics
• The law of segregation
• The law of independent assortment
• Locus/allele
• Dominant/recessive
• Incomplete dominance
• Epigenetic inheritance
• Mutation
• cis/trans regulatory elements
• in-frame/frameshift mutation
The sources of
genetic variations
• Mendelian genetics
• Transmission genetics
• Variation and mutation
• Mutation rates and
fitness consequences
Darwin did not understand the
mechanism of inheritance

biography.com
Gregor Mendel (1822-1884)
 Mendel’s laws of inheritance

l Law of segregation
l Law of independent assortment
 Law of segregation

• Each parent has two copies (alleles) of a gene,

which separate with equal probability into
gametes

• Alleles can be dominant or recessive

 Law of segregation
Yellow allele is dominant
Green is recessive
What about the next generation?

What is the frequency of green peas expected?

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No blending here! Green is restored
from two yellow parents

F1 F2

25%
Law of independent assortment

• The allele that gets passed down to the next

generation at one locus is independent of the
allele that gets passed down at another locus,
provided the loci are ‘unlinked’ (physically far
away)
 Law of independent assortment
(in modern genetic terms)

Rugosity
locus

Color locus

Chromosome 1 Chromosome 2
 Types of gamete from this
double heterozygote

• 50% of the gametes will be carrying the yellow allele;

50% will be green
• 50% will be carrying the rough allele and 50% the
smooth allele
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 Mendel’s laws of inheritance
Mendel’s laws resolved core
challenges to Darwin’s theory:

• Darwin and others had envisioned

inheritance as a blending process
• But with a blending process it is
difficult to maintain variability over
time
• Particulate inheritance explains
how variability can be maintained
over time
 How does the particulate nature of
inheritance operate at the molecular level?

• Once Mendel’s laws were discovered, the

molecular mechanisms of inheritance remained
unknown
The sources of
genetic variations
• Mendelian genetics
• Transmission genetics
• Variation and mutation
• Mutation rates and
fitness consequences
DNA and chromosomes
We have around 30,000 genes and 3 billion bases of DNA in
our haploid genome (from only one set of chromosomes)

What is a gene? 26
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• Abundance of regulatory ncRNA species versus protein coding
genes in the human genome. The numbers are based on
Gencode V17 (http://www.gencodegenes.org/releases/17.html)
 DNA
molecule
has 4
types of
nucleotide
Transcription: DNA to
mRNA
Mature mRNA processing
(in Eukaryotes)
Translation: mRNA to
protein
 The
genetic
code
 The
genetic
code

Example: AUG CGG AUU AAA AUA UCC UAA

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Phenotype
Where did all this diversity come from?
The sources of
genetic variations
• Mendelian genetics
• Transmission genetics
• Variation and mutation
• Mutation rates and
fitness consequences
Sources of new genetic variation in
populations

• Mutation

• Recombination

• Migration

• Lateral gene transfer

Sources of new genetic variation
in populations

• Mutation
We’ll talk about these today
• Recombination
• Migration
• Lateral gene transfer
Mutation

• A change to
the DNA
sequence of
an organism
• Primary source
of all genetic
variation
 Mutation
Mutations can be
• Spontaneous: caused by factors endogenous
to the organism, e.g., DNA copying errors
• Induced: caused by factors exogenous to the
organism, e.g., environmental chemicals and
radiation
 Types of mutation
Non-exhaustive list

l Base substitution
l Base insertion
l Base deletion
l Chromosomal duplication
l Chromosomal deletion
l Chromosomal inversion
l Chromosomal translocation
l Chromosomal fusion
l Addition of entire set of chromosomes
l Loss of entire set of chromosomes
 Types of mutation
Non-exhaustive list:

l Base substitution
l Base insertion
l Base deletion
l Chromosomal duplication
l Chromosomal deletion
l Chromosomal inversion
l Chromosomal translocation
l Chromosomal fusion
l Addition of entire set of chromosomes
l Loss of entire set of chromosomes
Mutations: substitution
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Not all mutations have an affect on the phenotype
The genetic code is redundant
Mutations in non-protein coding regions of
DNA can alter gene expression
Many sequences are regulatory (cis-
regulatory elements)

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 Mutation
Types of mutation (non-exhaustive list):
l Base substitution

l Base insertion

l Base deletion

l Chromosomal duplication

l Chromosomal deletion

l Chromosomal inversion

l Chromosomal translocation

l Chromosomal fusion

l Addition of entire set of chromosomes

l Loss of entire set of chromosomes

Duplic
Inversion
Translocation
Mutations at chromosome level
Chromosome variation
in Hominids and Great
Apes
Humans, Neanderthals
and Denisovans have
only 23 pairs of
chromosomes. All other
members of Hominidae
and Great Apes have 24
pairs of chromosomes
 Types of mutation
Non-exhaustive list:

l Base substitution
l Base insertion
l Base deletion
l Chromosomal duplication
l Chromosomal deletion
l Chromosomal inversion
l Chromosomal translocation
l Chromosomal fusion
l Addition of entire set of chromosomes
l Loss of entire set of chromosomes
The sequencing of the first Han Chinese (in 2008) showed a
remarkable number of DNA variations with the reference
genomes available (Venter and Watson’s genomes)

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 Lots of new single nucleotide polymorphisms
(SNPs) and small insertions/deletions (INDELs)

SNPs INDELs

dbSNP is a public
Database of genetic
Wang et al. 2008 (Nature) variation across species
 2,682 new structural variants at
the chromosome level

DGV: database of genomic variants; TEs: transposable elements

Wang et al. 2008 (Nature)

 Sources of new genetic variation

• Mutation

• Recombination

• Migration

• Lateral gene transfer

Recombination remixes existing DNA
sequence variation during Meiosis
The sources of
genetic variations
• Mendelian genetics
• Transmission genetics
• Variation and mutation
• Mutation rates and
fitness consequences
 Frequency of mutations

Human genome has around 3x109 bases (Haploid genome; 3 billion bases)

How many new mutations do we pass on to

our offspring when we reproduce?
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 Mutations are produced randomly or
undirected, not to meet particular needs
Induced Mutation (Acquired Immunity) Hypothesis

Luria and Delbrück’s experiment - only bacteria resistant

(immune) to bacteriophage T1 survive and form colonies
(A) If (B) If
mutations mutations
are induced arise
by the media, spontaneously
roughly the during cell
same divisions prior
number of to plating,
mutants are each plate will
expected to have a highly
appear on variable
each plate number of
mutants.
 The effect of mutations – why
most are neutral or deleterious
 Effect of mutations
• Most mutations can be expected to be neutral or
deleterious
• Unlikely for a chance mutation to lead to increase
the organism’s fitness (just as a random recipe
change would be unlikely to improve the cream
puff)
• But occasionally a mutation will increase the
organism’s fitness, i.e., increase its ability to
survive and reproduce. Although such mutations
are rare, they are essential to evolution
What is the effect of
100 mutations
introduced, in turn,
in Bacteriophage f1?

• Peris et al.
(2010) induced
random single
nucleotide
substitutions in
this virus

Black circle: mutation site

Roman number: gene
Colour: function
Most mutations are deleterious
or neutral
 Summary
• Mendelian genetics
– Particulate inheritance
– Law of segregation
– Law of independent assortment
• Transmission genetics
– DNA as a “recipe”
– DNA gets transcribed into RNA
– RNA translated into protein
– Genetic code provides mapping from nucleotides to amino acids
• Variation and mutation
– Mutations can be spontaneous or induced
– Multiple types of mutation
– Recombination
• Mutation rates and fitness consequences
– Mutations generally rare but crucial for evolution
– Mutations mostly neutral or deleterious; occasionally beneficial
 Next lecture
Reading chapter 7
• How allele frequencies change over time in
populations

• Null models (Hardy-Weinberg) for estimating

when allele frequencies and changing

• Natural selection!

Take pre-lecture quiz #5 before 10:30

am on Monday