Molecular and Genomic Evolution

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Molecular and Genomic Evolution
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Molecular and Genomic Evolution

• Genomes and Their Evolution
• The Evolution of Macromolecules
• Determining and Comparing the Structure of
  Macromolecules
• Proteins Acquire New Functions
• The Evolution of Genome Size
• The Uses of Molecular Genomic Information

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Genomes and Their Evolution

• An organisms genome is the full set of genes it
  contains.
• In eukaryotes, most of the genes are found in the
  nucleus, but genes are also present in plastids
  and chloroplasts.
• Genes are shuffled in every generation of
  sexually reproducing organisms via meiosis and
  fertilization.

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Genomes and Their Evolution

• For a gene to be passed on to successive
  generations, the individual with that gene must
  survive and reproduce.
• A genes capacity to cooperate with different
  combinations of other genes will likely increase
  its probability of transmission.
• The genes of an individual can be viewed as
  interacting members of a group in which there are
  divisions of labor and strong interdependencies.

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Genomes and Their Evolution

• Studies of genomic evolution look at the genome
  of an organism as an integrated whole and attempt
  to answer questions such as
• How do proteins acquire new functions?
• Why are the genomes of different organisms so
  variable in size?
• How has the enlargement of genomes been
  accomplished?

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The Evolution of Macromolecules

• The molecules of interest to molecular
  evolutionists are nucleotides, nucleic acids,
  amino acids, and proteins.
• Molecular evolutionists investigate the evolution
  of these macromolecules to determine how rapidly
  they change and why they have changed.
• Knowledge of the rate of change of a given
  macromolecule is crucial to attempts to
  reconstruct the evolutionary history of groups of
  organisms.

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The Evolution of Macromolecules

• Nucleic acids evolve when nucleotide base
  substitutions occur.
• Substitutions can change the amino acid sequence,
  and thus the structure and function, of the
  polypeptides.
• By characterizing nucleic acid sequences and the
  primary structures of proteins, molecular
  evolutionists can determine how rapidly these
  macromolecules have changed and why they changed.

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The Evolution of Macromolecules

• Molecular evolution differs from phenotypic
  evolution in one important way In addition to
  natural selection, random genetic drift and
  mutation exert important influences on the rates
  and directions of molecular evolution.
• A mutation is any change in the genetic material.

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The Evolution of Macromolecules

• Many mutations, called silent or synonymous
  mutations, do not alter the proteins they encode.
• This is because most amino acids are specified by
  more than one codon in the universal genetic
  code.
• For example, leucine is specified by six
  different codons UUA, UUG, CUU, CUC, CUA, and
  CUG.
• Since silent mutations are unlikely to be
  influenced by natural selection, they are free to
  accumulate in a population over time at rates
  determined by rates of mutation and genetic drift.

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The Evolution of Macromolecules

• A nonsynonymous mutation does change the amino
  acid sequence.
• For example, UUA to UUC would result in a
  phenylalanine rather than a leucine in the
  protein.
• Nonsynonymous mutations are usually deleterious,
  but those that dont alter the proteins shape
  may be selectively neutral.
• Most natural populations of organisms harbor much
  more genetic variation than would be expected if
  genetic variation were influenced primarily by
  natural selection.

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Figure 26.1 When One Base Does or Doesnt Make a
Difference
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The Evolution of Macromolecules

• In 1968, Motoo Kimura proposed the neutral theory
  of molecular evolution.
• The neutral theory postulates that, at the
  molecular level, the majority of mutations are
  selectively neutral.
• If so, the majority of evolutionary changes in
  macromolecules, and much of the genetic variation
  within species, result from neither positive
  selection of advantageous alleles nor stabilizing
  selection, but from random genetic drift.

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The Evolution of Macromolecules

• Using the rationale that the rate of fixation of
  mutation is theoretically constant and equal to
  the neutral mutation rate, the concept of the
  molecular clock was developed.
• The concept of the molecular clock states that
  macromolecules should diverge from one another at
  a constant rate.

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Determining and Comparing theStructure of
Macromolecules

• Biologists must determine the precise structure
  of macromolecules to investigate patterns of
  molecular evolution.
• PCR allows biologists to amplify ancient DNA to
  concentrations that can be used in experiments to
  determine its sequence.
• When the amino acid sequences of proteins from
  different organisms have been determined, they
  can be compared by sequence alignment.

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Figure 26.2 Amino Acid Sequence Alignment (Part
1)
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Figure 26.2 Amino Acid Sequence Alignment (Part
2)
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Determining and Comparing theStructure of
Macromolecules

• Once the amino acid sequences have been aligned,
  they can be compared.
• A similarity matrix can be constructed by adding
  up the number of similar and different amino
  acids in the sequences.
• The longer the molecules have been evolving
  separately, the more differences they will have.
• Substitution rates are highest at codon sites
  that do not change the amino acid being
  expressed, and in pseudogenes.

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Figure 26.3 Rates of Base Substitution Differ
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Determining and Comparing theStructure of
Macromolecules

• The much slower rate of mutation at sites that do
  affect molecular function is consistent with the
  view that most nonsynonymous mutations are
  disadvantageous and are eliminated from the
  population by natural selection.
• In general, the more essential a molecule is for
  cell function, the slower the rates of its
  evolution.
• A molecule that illustrates this principle is the
  enzyme cytochrome c, a component of the
  respiratory chain in mitochondria.

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Figure 26.4 Amino Acid Sequence of Cytochrome c
(Part 1)
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Figure 26.4 Amino Acid Sequence of Cytochrome c
(Part 2)
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Determining and Comparing theStructure of
Macromolecules

• To function as a molecular clock, a macromolecule
  would need to evolve at an approximately constant
  rate in all evolutionary lineages.
• Cytochrome c sequences have evolved at a
  relatively constant rate.
• Many other proteins show similar consistency in
  the rate at which they have changed over time,
  but not all molecules change at the same rate.

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Figure 26.5 Cytochrome c Has Evolved at a
Constant Rate
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Determining and Comparing theStructure of
Macromolecules

• Organisms with short generation times generally
  have faster rates of molecular evolution than
  organisms with longer generation times.
• Shorter generations result in more rounds of DNA
  replication and thus more opportunity for errors
  in replication.
• The rate of substitution per base per year in
  introns is 2 to 4 times greater in rodents than
  in primates.

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Proteins Acquire New Functions

• Evolution would not have been possible if
  proteins were unable to change their functional
  roles.
• Evidence indicates that all living organisms
  arose from a single ancestral lineage.
• Thus the many thousands of different functional
  genes that exist today must have arisen from a
  small number of ancestral genes.

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Proteins Acquire New Functions

• The most important process enabling proteins to
  acquire new functions appears to be gene
  duplication.
• Gene duplication may involve part of a gene, a
  single gene, parts of a chromosome, or whole
  chromosomes.
• Polyploidy, the duplication of an entire genome,
  has been important in speciation.
• Autopolyploid individuals avoid imbalances in
  gene expression because all of their chromosomes
  are duplicated.

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Proteins Acquire New Functions

• Evolution of a new function for a protein
• Lysozyme is an enzyme found in almost all
  animals it digests bacterial cell walls and is
  the first line of defense against invading
  bacteria.
• In mammals, a mode of digestion known as foregut
  fermentation has evolved twice. Bacteria in the
  foregut break down ingested plant matter by
  fermentation.
• In foregut fermenting animals, lysozyme has been
  modified to play a nondefensive role.
• The enzyme ruptures some of the bacteria that
  live in the foregut, releasing nutrients that the
  animal absorbs.

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Table 26.1 Similarity Matrix for Lysozyme in
Mammals
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Proteins Acquire New Functions

• Five amino acid substitutions are shared by
  foregut fermenters (cow and langur).
• The substitutions make it more resistant to the
  pancreatic enzyme trypsin and the acidic
  conditions of the stomach.
• Similar substitutions of hoatzin lysozyme have
  occurred to provide a similar function as cow and
  langur lysozyme.
• These three groups of animals independently
  evolved a similar molecule that enables them to
  recover nutrients from their fermenting bacteria.

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The Evolution of Genome Size

• The size and composition of the genomes of many
  species show much variation.
• Multicellular organisms have more DNA than
  single-celled organisms.
• Generally, more complex organisms have more DNA
  than less complex organisms.

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Figure 26.7 Complex Organisms Have More Genes
than Simpler Organisms
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The Evolution of Genome Size

• Some of the apparent differences in genome size
  disappear when the portion of DNA that actually
  codes for RNA or protein is compared.
• The size of the coding genome varies in a way
  that makes sense
• Eukaryotes have more coding DNA than
  prokaryotes.
• Plants have more than single-celled organisms.
• Vertebrates have more than nonvertebrates.

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The Evolution of Genome Size

• Most of the variation in genome size is due to
  the amount of noncoding DNA an organism has.
• Much of the noncoding DNA may consist of
  pseudogenes that are carried with the genome
  because the cost of doing so is small.
• Some of the DNA consists of transposable elements
  that spread through populations because they
  reproduce faster than the host genome.

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Figure 26.8 A Large Proportion of DNA Is
Noncoding
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The Evolution of Genome Size

• Retrotransposons are being used by scientists to
  determine the rates at which species lose DNA.
• The most common type carries long terminal
  repeats (LTRs) at each end.
• Occasionally, LTRs join together in the host
  genome, causing the DNA between them to be
  excised and leaving one of the LTRs behind.
• The number of these orphaned LTRs in a genome
  is a measure of how many retrotransposons have
  been lost.
• Scientists can use the number of LTRs present in
  the genomes of different organisms to compare
  their rates of DNA loss.

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The Evolution of Genome Size

• Two identical copies of a gene can have one of
  three different fates
• Both copies may retain their original function.
• One copy may become incapacitated by the
  accumulation of deleterious mutations and become
  a pseudogene.
• One copy may retain its original function while
  the other accumulates enough mutations that it
  can perform a different function.
• The third is the most significant for evolution.

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The Evolution of Genome Size

• The frequency of gene duplications and their
  outcome can be assessed by counting the number of
  synonymous nucleotide base changes in the genome
  and then comparing that with the number of base
  changes causing protein alterations.
• The rates of gene duplication are fast enough for
  a yeast or Drosophila population to acquire
  several hundred duplicate genes over the course
  of a million years.
• Although most duplicate genes disappear rapidly
  on an evolutionary time scale, some duplications
  lead to the evolution of genes with new functions.

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The Evolution of Genome Size

• Several rounds of duplication and mutation may
  lead to formation of a gene family, a group of
  homologous genes with related functions.
• There is evidence that the globin gene family
  arose by gene duplication.
• To estimate the time of the first globin gene
  duplication, a gene tree can be created.
• Based on the gene tree, the two globin gene
  clusters are estimated to have split about 450
  mya.

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Figure 26.9 A Globin Family Gene Tree
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The Uses of Molecular Genomic Information

• Molecules that have evolved slowly can be used to
  estimate relationships among organisms that
  diverged long ago.
• Molecules that have evolved rapidly are useful
  for studying organisms that share recent common
  ancestors.
• To determine the molecular evolutionary
  relationships of all existing animals, a molecule
  that all organisms possess must be used, such as
  rRNA.

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The Uses of Molecular Genomic Information

• rRNA has evolved very slowly because even minor
  changes in its base sequence result in inactive
  ribosomes.
• Differences among the rRNAs of living organisms
  can be used to estimate the timing of lineage
  splits.
• Molecular, morphological, and fossil data are
  regularly used in combination to create a
  phylogeny.
• The more characters that are used to create a
  phylogeny, the more accurate it will be.

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The Uses of Molecular Genomic Information

• Genes found in different organisms that arose
  from a single gene in their common ancestor are
  called orthologs.
• Genes that are related through gene duplication
  events in a single lineage are called paralogs.
• All of the genes in the engrailed gene family are
  orthologs.
• Paralogous engrailed genes have been generated in
  some lineages as a result of duplication events.

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Figure 26.10 Phylogeny of the Engrailed Genes
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The Uses of Molecular Genomic Information

• Understanding the genomes of pathogens and the
  organisms that carry them has already had medical
  benefits.
• The determination of the genomes of Anopheles and
  Plasmodium has allowed scientists do develop
  transgenic mosquitoes that express an
  anti-Plasmodium molecule that makes them
  inefficient vectors of malaria in the lab.
• Information provided by the genomic sequence of
  Treponema pallidum, the bacterium that causes
  syphilis, is being used to develop a vaccine
  against this disease.

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The Uses of Molecular Genomic Information

• The AIDS epidemic reminds us that molecular data,
  while providing powerful tools in our struggle
  with diseases, cannot solve all medical problems.
• A highly active antiretroviral therapy (HAART) is
  generally used to treat AIDS patients.
• Unfortunately, strains of resistant HIV develop
  in the blood of most patients that receive HAART.
• The combination of a high mutation rate and no
  repair mechanism means that a new mutant is
  generated every time HIV replicates its genome.

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The Uses of Molecular Genomic Information

• Scientific understanding of the evolutionary
  patterns of life on Earth and how the agents of
  evolution governed those patterns is advancing
  more rapidly than ever.
• By combining molecular data with information from
  the fossil record, biologists are developing an
  increasingly comprehensive picture of the
  evolution of life on Earth.