4 Mechanisms of evolution

 Mutations
 Small effect, but impact across generations
 Natural selection.
 Differential survival and reproduction
 Allelic/genetic drift
 Random loss of alleles from (small) populations
 Allele/gene flow
 Random movement of alleles among populations
 Natural Selection

THE ONLY FORCE THAT LEADS TO ADAPTATION!

 Natural Selection

What happens to variation?

Maintaining genetic and phenotypic
variation
 Diploidy
 Heterozygote advantage
 Selection in varying environments
 Frequency dependent selection
 Some alleles are neutral
 Sexual reproduction
Diploidy:
Peppered Moth and Industrial Revolution
Sickle Cell Hemoglobin
Evolution of Antibiotic Resistance
Evolution of antibiotic resistance to TB
1000-year-old mummy
from Peru

The nodules in the lung tissue

indicate that the woman died
from tuberculosis
Antibiotics
How Bacteria Become Resistant

5. Mutation on target protein

prevents antibiotic binding
VGT
(rifampicin)
Decline in Tuberculosis between 1950 and 1990
 Antibiotics!
 Rifampicin effectively killed the TB bacterium
 Became not an important problem in developed countries
 In the late 1980s TB infections surged dramatically (HIV
immuno-suppression)
 The strains responsible for the increase were resistant to
rifampicin
 Sequencing of the resistant strain showed a point mutation
in the gene that codes for a component of the the RNA
polymerase.
 Since then, point mutations involving several different bases
have been identified, all conferring resistance to this
antibiotic.
http://study.com/academy/le
sson/inhibitors-of-dna-rna-
synthesis-how-rifamycins-and-
quinolone-kill-bacteria.html
Antibiotic Resistance and Vertical Gene Transfer
Your Example in Lab
 Advantageous alleles passed from one generation
to the other
 Only source of variation is mutation
 Only via reproduction, not across species
Misuse of Antibiotics
Just a year after the war’s end, though, the discoverer of penicillin
warned that it might become useless. Accepting his Nobel Prize in
1945, Alexander Fleming mapped out how the failure could
happen. “There is the danger that the ignorant man may easily
underdose himself,” Fleming said, “and by exposing his microbes
to non-lethal quantities of the drug make them resistant.”
 Enter Superbugs…

What is a Superbug?
A Pathogen Resistant to More Than One Antibiotic
Simultaneously
How do Superbugs become Superbugs? They acquire
new resistance genes from other bacteria
 Plasmids

•Plasmids are extrachromosomal (usually) circular molecules of

DNA
•They are not considered chromosomes because:
•They replicate independently from the chromosome
•There can be many copies of them
•They carry non-essential genes (antibiotic resistance,
metabolism of unusual nutrients, etc.
Antibiotic Resistance and Horizontal Gene
Transfer
 Bacteria can exchange DNA even in the absence
of sexual reproduction
 Three ways:
 Conjugation
 Transduction
 Transformation (competence)
 If antibiotic resistance genes are passed via HGT,
they can be transmitted from one strain to another
as well as from one species to another!!!!
Horizontal Gene Transfer

Review your lab background!!!!

MDR-TB
 Refers to Tuberculosis strains that are
resistant to at least two antibiotics:
 Isoniazid
 rifampicin
 MRSA
 MRSA. Methicillin resistant Staphylococcus aureus. Resistance to beta-
lactam antibiotics which include the penicillins (methicillin, dicloxacillin,
nafcillin, oxacillin, etc.) and the cephalosporins.
 First strain described early ’60. Resistant to one antibiotic. Today strains
resistant to several antibiotics are circulating.
 S. aureus is a Gram positive bacterium that causes normal skin infections.
Sometimes can be deadly. ~19,000 people/year die.
 Originally Nosocomial. Acquired in hospitals, where people have open
wounds or immuno-compromised. Now also community acquired.
 Resistance genes found in mobile genetic elements that can move from
strain to strain.
 Overuse of antibiotics has caused the problem.
 A Superbug Is Born
 2002, dialysis patient infected with three bacteria:
MRSA, VRE and VRSA
 Genetic analysis showed that the VRSA was a
new bacterium that evolved within the patient.
 VRSA was a MRSA that had acquired vancomycin
resistance from the VRE.
 The gene was transferred via a mobile genetic
element (Plasmid) that carried resistance for three
other antibiotics as well.
Combination Drugs Regimens and Compliance

 To avoid the evolution of drug resistant strains you have to

understand biological evolution
 Antibiotics misuse and overuse are the main cause for the
evolution of resistant strains. Not overusing is a solution to the
problem.
 “Combination regimens” is another way to prevent resistance.
 The chances that a single bacterium (or other pathogen) will
become SIMULTANEUSLY resistant to three or four drugs are
extremely low
 If a patient does not comply, it promotes the evolution of multiple
antibiotic resistance.
 Non-compliance is normal especially for regimens that last a long
time!!
Combination Drugs Regimens
Microbe susceptible to Drug A
Mutant resistant to Drug A

Resistant to Drug B
Resistant to Drug C
Resistant to Drug D
TB Standard Regimen
 The Cost of Mutations

Would relieving the selective pressures help

revert populations to the susceptible
phenotype?
Compensatory Mutations

Resistance Resistance + Compensatory

HGT and Virulence Factors
 First described in 1982. Hamburger outbreak of
gastrointestinal disease.
 The genome of all other E. coli strains contains
~4,500 genes (4.6 million bp); E. coli O157:H7
contains ~5,400 (5.4 mi9llion bp)
 Horizontally acquired a genomic island from
Shigella containing genes the code for bacterial
Toxins responsible for damaging the lining of the
intestine.
Shiga Toxins
Overuse and Misuse of
Antibiotics
 Antibiotics misused, for example, viral
infections
 Antibiotics overused, for example, for
prevention
 Lack of patient compliance
 Use in animal industry
Predicted Deaths Due to
Antibiotic Resistance by 2050
UN Recommendations
4 Mechanisms of evolution
 Mutations
 Small effect, but impact across generations
 Natural selection.
 Differential survival and reproduction
 Allelic/genetic drift
 Random loss of alleles from (small) populations
 Allele/gene flow
 Random movement of alleles among populations
 Allelic Drift
 Change in the allele frequencies in a population
that is due to random chance (Sampling error).
 Much more pronounced in small populations.
 Drift leads to a reduction in genetic variation and can cause the
loss of alleles, or “fixation” of alleles. Types are: a founder and
bottleneck effects.
Example of Bottleneck

Cheetah range in 1900

Cheetah range today

 SURVEYING ALLELIC DIVERSITY IN POPULATIONS

1. Take blood samples from many

individuals and isolate proteins.

2. Load protein samples from

different individuals into wells
in gel.

3. Put gel into an electric field.

Proteins separate according to
charge and mass.

4. Treat gel with a solution that

stains a specific enzyme. One
band implies that the individual
is homozygous at the locus for
the enzyme. Two bands imply that
the individual is heterozygous at
this locus.
Observe the lack of allele diversity in cheetahs:

All cheetahs are homozygous at this locus Many lions are heterozygous at this locus
Founder Effect
 Founder effect
 Amish population in Pennsylvania tend to marry
and have children within the population
 Settled from a few individuals in mid-1800s

1 in 14 Amish carry a recessive allele for short

arms and legs and extra fingers and toes (Ellis-
van Creveld syndrome)

1 in 1000 Americans outside this population

have the same recessive allele
5 Mechanisms of evolution
 Mutations
 Small effect, but impact across generations
 Natural selection.
 Differential survival and reproduction
 Allelic/genetic drift
 Random loss of alleles from (small) populations
 Allele/gene flow
 Random movement of alleles among populations
 Non-random mating
 Changes on phenotype frequencies
 Gene Flow Is a Homogenizing Agent.
Reduces Genetic Differences Between Populations

Great Wall of China

Reduces allele flow between plant

populations
Speciation
The Biological Species Concept is Based on
Reproductive Isolation
A species is a population or group of populations whose
members can interbreed with with each another in nature
and produce viable, fertile offspring; but cannot produce
viable, fertile offspring with members of other species
A BIOLOGICAL SPECIES IS THE LARGEST SET OF
POPULATIONS IN WHICH GENETIC EXCHANGE IS
POSSIBLE AND THAT IS GENETICALLY ISOLATED FROM
OTHER SUCH POPULATIONS
 The Biological Species Concept Has Some
Major Limitations
 Extinct species represented by fossils
 Lack of information about interbreeding
 Entirely asexual forms like bacteria
 Speciation is an on-going process. Hybrids: examples of
speciation in progress
The Biological Species Concept Has Limitations

 Species are also defined based on alternative

concepts:
 The morphospecies concept characterizes
species in terms of unique set of structural
and biochemical features.
 The phylogenetic species concept is based
on reconstructing the evolutionary history of
populations.
Speciation and Barriers to Gene Flow

In this lecture I will address speciation strictly under the

“biological species concept”
Speciation as the study of the causes and evolution of
barriers to gene flow
 The Darwinian Value of Speciation
 Speciation is the process that blocks gene flow between populations.
Genes from one species do not enter the gene pool of another species.
 Speciation leads to genetic and morphological diversity between
populations because it counteracts the homogenizing effects of gene
flow.
 Speciation is important because divergence between populations allows
adaptation to different spatial habitats and to different resources which
in turn reduces their struggle for existence by diminishing competition
 Population Change
 Speciation is the outcome of isolation
and divergence.
 Isolation is created by barriers in gene
flow.
 Divergence is created when selection,
mutation, and genetic drift act on
populations separately.
Allopatric Speciation
 Two modes of speciation.
How reproductive isolation occurs
 Sympatry:
Selection against hybrids is the barrier to gene flow.

Hybrid not as well fit in any of the

two environments. Not competitive.
Gene that makes them migrate
and/or makes them mate with the
other kind will not be passed to the
next generation. Reproductive
isolation.
 Example:
Cichlid Fish in African Lakes
 Example:
Cichlid Fish in African Lakes
 Example:
Cichlid Fish in African Lakes