Lecture 18 Evolution and human health - University of ...€œevolutionary arms race”. The evolution of flu viruses • the evolution of viruses and their hosts is a form of antagonistic

Lecture 18 Evolution and human health

Evolution and human health

1. Genetic factors 2. Infectious diseases


1. Genetic factors


1. Genetic factors

P – Point mutation, or any insertion/deletion entirely inside one gene D – Deletion of a gene or genes C – Whole chromosome extra, missing, or both (see Chromosome abnormality) T – Trinucleotide repeat disorders: gene is extended in length Disorder Mutation Chromosome 22q11.2 deletion syndrome D 22q Angelman syndrome DCP 15 Canavan disease 17p Charcot–Marie–Tooth disease Color blindness P X Cri du chat D 5 Cystic fibrosis P 7q Down syndrome C 21 Duchenne muscular dystrophy D Xp Haemochromatosis P 6 Haemophilia P X Klinefelter syndrome C X Neurofibromatosis 17q/22q/? Phenylketonuria P 12q Polycystic kidney disease P 16 (PKD1) or 4 (PKD2) Prader–Willi syndrome DC 15 Sickle-cell disease P 11p Spinal muscular atrophy DP 5q Tay–Sachs disease P 15 Turner syndrome C X

P – Point mutation, or any insertion/deletion entirely inside one gene D – Deletion of a gene or genes C – Whole chromosome extra, missing, or both (see Chromosome abnormality) T – Trinucleotide repeat disorders: gene is extended in length Disorder Mutation Chromosome 22q11.2 deletion syndrome D 22q Angelman syndrome DCP 15 Canavan disease 17p Charcot–Marie–Tooth disease Color blindness P X Cri du chat D 5 Cystic fibrosis P 7q Down syndrome C 21 Duchenne muscular dystrophy D Xp Haemochromatosis P 6 Haemophilia P X Klinefelter syndrome C X Neurofibromatosis 17q/22q/? Phenylketonuria P 12q Polycystic kidney disease P 16 (PKD1) or 4 (PKD2) Prader–Willi syndrome DC 15 Sickle-cell disease P 11p Spinal muscular atrophy DP 5q Tay–Sachs disease P 15 Turner syndrome C X


1. Genetic factors

Sex-linked diseases: Haemophilia

Haemophilia – the royal disease

Lady Gouldian Finches - Erythrura gouldiae

Sex autosome Red head: Male R-R or R-b

Female R-o Black head Male b-b

Female b-o Orange head Male R-R or R-b or-or

Female R-o or-or

Sex Chromosomes Male ZZ Female ZW

Clustered regularly interspaced short palindromic repeats (CRISPR)

"Go hang a salami I'm a lasagna hog.", "Dammit, I'm mad!"


1. Genetic factors 2. Infectious diseases

The evolution of flu viruses


Check out: http://www.google.org/flutrends/

Google Flu Trends data US data


• the evolution of viruses and their hosts is a form of antagonistic coevolution.



• host-pathogen coevolution is also referred to as an “evolutionary arms race”.



• host-pathogen coevolution is also referred to as an “evolutionary arms race”.

y

z Host Pathogen

Adaptation

Counter Adaptation



• host-pathogen coevolution is also referred to as an “evolutionary arms race”. Example: the influenza A virus




• influenza A is a retrovirus with 11 genes (on 8 RNA strands).




• influenza A is a retrovirus with 11 genes (on 8 RNA strands).

• responsible for annual flu epidemics (killing about 30,000 to 35,000 Americans per year).

Influenza A virus also causes serious global pandemics:


Year Deaths in US Spanish flu 1918 500,000

Egon Schiele



Asian flu 1957 60,000



Asian flu 1957 60,000

Hong Kong flu 1968 80,000

The influenza A virus

H N

The influenza A virus

H N

The evolution of antigenic sites


• influenza A’s major coat protein is hemagglutinin.


• influenza A’s major coat protein is hemagglutinin. • hemagglutinin is the main target of our immune system.


• influenza A’s major coat protein is hemagglutinin. • hemagglutinin is the main target of our immune system. • amino acid sites in hemagglutinin that our immune system recognizes (and remembers) are called antigenic sites.

Locations of antigenic sites in hemagglutinin molecule

Phylogenetic analysis of influenza A

Phylogenetic analysis of influenza A • Fitch et al. (1991) examined the phylogenetic relationships among flu strains over a 20-year period using hemagglutinin sequences.


Walter M. Fitch 1929 – 2011


• this is equivalent to 20 million years of human evolution!

Hemagglutinin evolved at a constant rate!


Is this neutral evolution?


Is this neutral evolution? NOT LIKELY!

Annual flu epidemics arise from a single lineage!

Why did only a single flu strain persist?

Why did only a single flu strain persist? • due to differences in mutations at antigenic vs. non-antigenic sites?


Surviving Extinct lineage lineages



antigenic sites 33 31




non-antigenic sites 10 35





43 66





43 66 Conclusion: The surviving lineage had significantly more mutations at antigenic sites

Positive selection in the hemagglutinin gene


• positive selection occurs when the rate of replacement substitution exceeds the rate of silent substitution.


• positive selection occurs when the rate of replacement substitution exceeds the rate of silent substitution. • in influenza A, there are 18 codons exhibiting higher rates of replacement substitution!


• positive selection occurs when the rate of replacement substitution exceeds the rate of silent substitution. • in influenza A, there are 18 codons exhibiting higher rates of replacement substitution! • why is this important?


• positive selection occurs when the rate of replacement substitution exceeds the rate of silent substitution. • in influenza A, there are 18 codons exhibiting higher rates of replacement substitution! • why is this important? • because this allows us to predict surviving strains and thus make flu vaccines!

Strains that persist have the most changes in hemagglutinin antigenic sites

A phylogeny of influenza A based on the nucleoprotein gene

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Influenza A can move between humans, birds, and pigs

Where did H3 come from?

Ñ

H3 jumped into humans from birds

Influenza A can move between humans, birds and pigs

The origin of pandemic flu strains

Human strain Bird strain Ø ×

Recombination in swine host Ô

Reinfect human host

H1N1 is a triple-reassortment virus

H1N1 is a triple-reassortment virus

Segment Origin PB2 Avian North America PB1 Human circa 1993 PA Swine Eurasia HA Swine North America NP Swine Eurasia NA Swine Eurasia MP Swine Eurasia NS Swine Eurasia

The evolution of virulence


• virulence is a term that describes the effect a pathogen has on its host.


• virulence is a term that describes the effect a pathogen has on its host. high virulence → major effect on host’s fitness


• virulence is a term that describes the effect a pathogen has on its host. high virulence → major effect on host’s fitness low virulence → minor effect on its host’s fitness


• virulence is a term that describes the effect a pathogen has on its host. high virulence → major effect on host’s fitness low virulence → minor effect on its host’s fitness Example: rabbits and the myxoma virus in Australia


Example: rabbits and the myxoma virus in Australia


Example: rabbits and the myxoma virus in Australia • in 1859, 12 rabbits were bought by Mr. Thomas Austin.


Example: rabbits and the myxoma virus in Australia • in 1859, 12 rabbits were bought by Mr. Thomas Austin. • 6 years later, there were 30,000!


Example: rabbits and the myxoma virus in Australia • in 1859, 12 rabbits were bought by Mr. Thomas Austin. • 6 years later, there were 30,000! • they escaped from his farm and exploded in abundance all over the country.


Example: rabbits and the myxoma virus in Australia • in 1859, 12 rabbits were bought by Mr. Thomas Austin. • 6 years later, there were 30,000! • they escaped from his farm and exploded in abundance all over the country. • the myxoma virus was introduced in the 1950’s to control the rabbit population.



Virulence grade

high low

I II IIIa IIIb IV V



Virulence grade

high low

I II IIIa IIIb IV V 1950 100 0 0 0 0 0



Virulence grade

high low

I II IIIa IIIb IV V 1950 100 0 0 0 0 0 1964 0 0.3 26.0 34.0 31.3 8.3


• virulence is a term that describes the effect a pathogen has on its host. high virulence → major effect on host’s fitness low virulence → minor effect on its host’s fitness • three models have been proposed to account for the evolution of virulence.

1. The coincidental evolution hypothesis


• the virulence of many human pathogens is a result of selection acting on that pathogen in a different environment.


• the virulence of many human pathogens is a result of selection acting on that pathogen in a different environment. Example: tetanus


• the virulence of many human pathogens is a result of selection acting on that pathogen in a different environment. Example: tetanus • caused by a soil bacteria Clostridium tetani.


• the virulence of many human pathogens is a result of selection acting on that pathogen in a different environment. Example: tetanus • caused by a soil bacteria Clostridium tetani. • produces a deadly toxin not directed at humans but at something in the soil.

2. The short-sighted evolution hypothesis


• since pathogens reproduce within hosts, traits that increase their short-term fitness may actually be detrimental.



• the virus is “short-sighted” and virulence higher than expected.



• the virus is “short-sighted” and virulence higher than expected. Example: poliovirus.




• normally infects cells that line the digestive tract and cause few symptoms.




• normally infects cells that line the digestive tract and cause few symptoms. • occasionally, the virus infects cells of the nervous system with tragic consequences.

3. The trade-off hypothesis


• pathogens should evolve to the point where fitness costs to the host are balanced by its capacity to propagate itself to other hosts.


• pathogens should evolve to the point where fitness costs to the host are balanced by its capacity to propagate itself to other hosts. • pathogens may thus evolve to where they harm their hosts considerably.


• pathogens should evolve to the point where fitness costs to the host are balanced by its capacity to propagate itself to other hosts. • pathogens may thus evolve to where they harm their hosts considerably. An experiment: E. coli and the phage f1 by Messenger et al. (1999).


• pathogens should evolve to the point where fitness costs to the host are balanced by its capacity to propagate itself to other hosts. • pathogens may thus evolve to where they harm their hosts considerably. An experiment: E. coli and the phage f1 by Messenger et al. (1999). • phage f1 can propagate both vertically (parent to daughter cell) and horizontally (to a new host).

Treatment 1: 8 day vertical (ä) + brief horizontal (Ú)

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Treatment 2: 1 day vertical (ä) + brief horizontal (Ú) ä

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After 24 days measured:



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1. Phage virulence (growth rate of infected hosts).



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1. Phage virulence (growth rate of infected hosts).

2. Phage growth rate (rate of virion secretion from infected hosts).

Trade-off between virulence and reproductive rate in phage f1

What factors can select for increased virulence?


1. Live host not needed for transmission


1. Live host not needed for transmission Examples: ebola virus, parasitic fungi


1. Live host not needed for transmission Example: ebola virus, parasitic fungi 2. Multiple infections in same host


1. Live host not needed for transmission Example: ebola virus, parasitic fungi 2. Multiple infections in same host • leads to competition among pathogens within hosts


1. Live host not needed for transmission Example: ebola virus, parasitic fungi 2. Multiple infections in same host • leads to competition among pathogens within hosts 3. Transmission is “horizontal” (i.e., from

individual to individual), not “vertical” (i.e., parent to offspring)

Lecture 18 Evolution and human health - University of ...€œevolutionary arms race”. The evolution of flu viruses • the evolution of viruses and their hosts is a form of antagonistic

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