Evolution at the Molecular Level
Outline
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Evolution of genomes
 Review of various types and effects of
mutations
 How larger genomes evolve through
duplication and divergence
 Molecular archeology based on gene
duplication, diversification, and selection
globin gene family: an example of
molecular evolution
Speculations on how the first cell
arose

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The first step to life must have been a
replicator molecule
The original replicator may have been RNA


Ribozymes?
More complex cells and multicellular
organisms appeared > 2 billion years after
cellular evolution

Earliest cells
evolved into three
kingdoms of living
organisms
Archaea and
bacteria now
contain no introns
 Introns late
evolutionary
elaboration

Fig. 21.3
Basic body plans of some Burgess shale organisms
Many species resulting from metazoan explosion
have disappeared
Fig. 21.4
Evolution of humans

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35 mya – primates
6 mya – humans diverged from chimpanzees
Fig. 21.5
Evolution of Humans

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Human and chimpanzee genomes 99%
similar
Karyotypes almost same
No significant difference in gene function
Divergence may be due to a few thousand
isolated genetic changes not yet identified
Probably regulatory sequences
DNA alterations form the basis of
genomic evolution

Mutations arise in several ways
 Replacement of individual nucleotides
 Deletions / Insertions: 1bp to several Mb
 Single base substitutions
 Missense mutations: replace one amino acid codon with
another
 Nonsense mutations: replace amino acid codon with stop
codon
 Splice site mutations: create or remove exon-intron
boundaries
 Frameshift mutations: alter the ORF due to base
substitutions
 Dynamic mutations: changes in the length of tandem repeat
elements
Effect of mutations on population

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Neutral mutations are unaffected by agents
of selection
Deleterious mutations will disappear from a
population by selection against the allele
Rare mutations increase fitness
Genomes grow in size through
repeated duplications
 Some
duplications result from
transposition
 Other
duplications arise from
unequal crossing over

Genetic drift and mutations can turn
duplications into pseudogenes

Diversification of a duplicated gene followed
by selection can produce a new gene

Genome size
increases
through
duplication of
exons, genes,
gene families
and entire
genomes
Fig. 21.10
Basic structure of a gene
Fig. 21.11
Genes may elongate by duplication of exons to
generate tandem exons that determine tandem
functional domains
e.g., antibody molecule
Fig. 21.12a
Exon shuffling may give rise to new genes
e.g., tissue plasminogen activator (TPA)
Fig. 21.12b
Duplications of entire gene can
create multigene families
Fig. 21.13a
Unequal crossing over can expand and
contract gene numbers in multigene families
Fig. 21.13b
Fig. 21.14a
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Intergenic gene conversion can increase
variation among members of a multigene
family
One gene is changed, the other is not
Concerted evolution can lead to gene
homogeneity
Fig. 21.15
Unequal crossing over
Gene conversion
Evolution of gene superfamilies
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Large set of genes divisible into smaller sets,
or families
Genes in each family more closely rated to
each other than to other members of the
family
Arise by duplication and divergence
Evolution of globin superfamily
Fig. 21.16
Organisation of globin genes
Fig. 21.16
Developmental variation in gene expression
a-like chains - z & a
b-like
chains - e, g, d, b
Fig. 21.16
Adult human made of
a2b2 – 97%;
a2d2 - ~2%;
a2g2-~1% (fetal persistence)
Gene expression controlled by location
Fig. 21.16
e – embryonic yolk sac
g – yolk sac & fetal liver
b & d – adult bone marrow
Evolution of mouse globin superfamily
Fig. 21.16
Evolution of mouse globin superfamily
Fig. 21.16
The Haemoglobinopathies
Thalassemias
-Anaemias associated with impaired synthesis of Hb subunits
Thalassaemias can arise from different mutations causing a
disease of varying severity.
a0/b0 thalassaemias – globin chain absent
a+/b+ thalassaemias – normal globin chain in reduced amounts
a- thalassemias
a- thalassemias
deletion of one or both a globins in an a gene cluster
Severity depends on whether the individual has 1,2,3, or 4
missing a globin genes.
GENOTYPE
a+ a+ a+a+
a+a
a+a+
PHENOTYPE
Normal
Silent carrier
a+ a
a-thalassaemia trait
minor anaemic
conditions
HbH
Hydrops foetalis
mild – moderate anaemia
foetus survives until
around birth
a+a
a+a+ a a
a+a
aa
aa
aa
asymptomatic condition.
a-thalassaemia – 2
b- thalassemias
b- thalassemias
5’
Mutations in b globin cluster
are of different types
gene deletion
transcriptional mutation
RNA processing
mutations
RNA cleavage signal
mutations
Nonsense & frameshift
mutations
3’
Non coding regulatory regions
Exons
Introns (InterVening Sequences)
3’ cleavage mutant
deletion
RNA splicing mutant
transcription mutant
nonsense mutation
frameshift insertion
frameshift deletion
b- thalassemias
main genetic mechanisms that contribute to the
phenotypic diversity of the b-thalassaemias.