Evolution at the Molecular Level

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Evolution at the Molecular Level
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Outline

• 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

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Speculations on how the first cell arose

• 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 gt 2 billion years after cellular
  evolution

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• Earliest cells evolved into three kingdoms of
  living organisms
• Archaea and bacteria now contain no introns
• Introns late evolutionary elaboration

Fig. 21.3
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Basic body plans of some Burgess shale organisms
Many species resulting from metazoan explosion
have disappeared
Fig. 21.4
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Evolution of humans

• 35 mya primates
• 6 mya humans diverged from chimpanzees

Fig. 21.5
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Evolution of Humans

• 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

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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

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Effect of mutations on population

• Neutral mutations are unaffected by agents of
  selection
• Deleterious mutations will disappear from a
  population by selection against the allele
• Rare mutations increase fitness

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Genomes grow in size through repeated duplications

• Some duplications result from transposition
• Other duplications arise from unequal crossing
  over

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• Genetic drift and mutations can turn duplications
  into pseudogenes
• Diversification of a duplicated gene followed by
  selection can produce a new gene

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• Genome size increases through duplication of
  exons, genes, gene families and entire genomes

Fig. 21.10
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• Basic structure of a gene

Fig. 21.11
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Genes may elongate by duplication of exons to
generate tandem exons that determine tandem
functional domainse.g., antibody molecule
Fig. 21.12a
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Exon shuffling may give rise to new genese.g.,
tissue plasminogen activator (TPA)
Fig. 21.12b
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Duplications of entire gene can create multigene
families
Fig. 21.13a
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Unequal crossing over can expand and contract
gene numbers in multigene families
Fig. 21.13b
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Fig. 21.14a

• Intergenic gene conversion can increase variation
  among members of a multigene family
• One gene is changed, the other is not

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Concerted evolution can lead to gene homogeneity
Fig. 21.15
Unequal crossing over
Gene conversion
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Evolution of gene superfamilies

• 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

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Evolution of globin superfamily
Fig. 21.16
 
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Organisation of globin genes
Fig. 21.16
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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)
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Gene expression controlled by location
e embryonic yolk sac g yolk sac fetal
liver b d adult bone marrow
Fig. 21.16
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Evolution of mouse globin superfamily
Fig. 21.16
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Evolution of mouse globin superfamily
Fig. 21.16
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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

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a- thalassemias
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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 PHENOTYPE a a aa Normal aa
aa Silent carrier asymptomatic
condition. a-thalassaemia 2 a a
aa a-thalassaemia trait minor anaemic
conditions aa a a aa a
a HbH mild moderate anaemia a a a a
Hydrops foetalis foetus survives until
around birth
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b- thalassemias
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b- thalassemias

• Non coding regulatory regions
• Exons
• Introns (InterVening Sequences)
• 3 cleavage mutant
• deletion
• RNA splicing mutant
• transcription mutant
• nonsense mutation
• frameshift insertion
• frameshift deletion

• Mutations in b globin cluster are of different
  types
• gene deletion
• transcriptional mutation
• RNA processing mutations
• RNA cleavage signal mutations
• Nonsense frameshift mutations

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b- thalassemias
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main genetic mechanisms that contribute to the
phenotypic diversity of the b-thalassaemias.