Lecture 15 Evolutionary Medicine Flashcards
What is evolutionary medicine?
*Both hosts and pathogens are shaped by natural selection…
*Evolutionary medicine is the integrated study of evolution and medicine to improve scientific understanding of the reasons for disease and actions that can be taken to improve health
Aging
*Aging, the time-related deterioration of functions necessary for survival and reproduction, is observed across the animal kingdom
*In humans, aging is associated with a higher rate of certain diseases, such as cancer, heart disease, and Alzheimer’s disease
*Aging occurs as a result of natural selection on life history traits that impact on survival and reproduction…
*While mutations that cause death at an early age encounter strong negative selection, mutations that cause diseases after individuals have reproduced are protected from selection.
*Natural selection can furtherincrease the frequency of mutations associated with aging if those mutations also promote fitness early in life —antagonistic pleiotropy
*e.g. cardiovascular disease in humans:
*40/76 genes associated with cardiovascular disease shown to have signs of positive selection (Byarset al. 2017)
*Discuss with the person next to you: What are some possible traits these genes could be associated with? (5 mins)
“Old Friends” hypothesis
*Over the past few decades, there has been an increase in autoimmune disorders such as allergies and asthma
*The emergence of these disorders has coincided with the industrial revolution and improvements in public health
*The immune system has evolved a fine-tuned response to microbes it encounters within our bodies –quickly responding to certain dangerous microbes, but tolerating other beneficial microbes
*The immune system learnsthis tolerance in early life as it is exposed to microbes from birth
*Research that I have been involved in has shown a strong signal of maternal transmission of gut microbes (from mother to offspring) in natural mammalian population, with certain bacterial families showing a particularly strong signal (Waneliket al. 2023)
*However, modern life has disturbed this normal course of development, with children being exposed to fewer microbes.
*e.g. children are fed on formula, play in clean houses, frequently receive antibiotics etc.
*If a child isn’t exposed to microbes, they cannot help train the immune system -> “Old Friends” hypothesis
*Discuss with the person next to you: According to the “Old Friends” hypothesis, how might we tackle the rise in autoimmune disorders in industrialised countries? (5 mins
Evolution of virulence
*The harm that a pathogen causes its hosts is known as virulence
*e.g. cold vs. flu
*The virulence of a pathogen can evolve
*A pathogen replicates within its host, and traits that allow it to replicate faster increaseits fitness.
*However, the long-term fitness of a pathogen also depends on how likely it is to spread to the next host.
*The faster a pathogen uses up its host’s resources and replicates, the more harm it will do to its host. If its hosts dies too quickly, then it won’t have a chance to spread toits next host.
*This evolutionary trade-off between within-host replication and between-host transmission can stop a pathogen from becoming too virulent
*Discuss with the person next to you: What level of virulence (lower or higher) would you expect in these scenarios?
-stronger selection for competition within hosts
-stronger selection for movement across hosts
The evolving influenza virus
*In UK, flu is seasonal (peaks in winter) and can cause large numbers of deathsWhat is it?
*RNA virus: 8 RNA strands encode 11 proteins
*Hemagglutinin (HA) is a surface protein used to bind to cells of the nose, throat and lungs
*The virus uses the cell’s genetic machinery to produce many copies of itself (1 cell = 10,000 –1M new copies of viral genome)
what happens when a virus accumulates mutations very fast?
*Virus accumulates mutations veryfast during this time -> “mutant swarm”
*Some mutations detrimental, some beneficial
*Competition between genotypes
*As flu viruses experience ongoing selection, they can develop ways of escaping the host immune response..
*HA is the primary protein recognised, attacked, and remembered by host immune system = antigenic site
*Host produces Abs against HA
*HA protein can change so Abs don’t bind
*Changes can be so big that that Abs from one year are not effective next year -> antigenic drift
*Why we have to get flu vaccine each year
regarding flu vaccines
*Flu vaccines made of dead viruses/fragmentsthatstimulate the immune system to make Abs against HA
*The World Health Organization (WHO) coordinates a global influenza surveillance and response system
*This systemregularly characterises antigenic properties of influenza viruses. This is combined with genetic and epidemiological data to select strains for use in vaccine
*Takes months to create a newbatch of vaccines, a period during which the virus population can rapidly evolve
*So researchers have to make an informed guess about which strains are most likely to be effective in upcoming flu season.
*The resulting effectiveness of flu vaccines fluctuates between 40% –60%.
regarding a flu virus gaining new genetic variation
Flu virus can also gain new genetic variation through a process called reassortment.
*Thisoccurs when genetic segments from different influenza strains combine within a single individual.
*When human viruses combinewith viruses from other species this can lead to a more significant change –> antigenic shift.
problems with a hybrid virus
*Because ahybrid virus contains human-adapted genesit canspread quickly through the human population
*It can also go unnoticed by Abs that target human strains if its surface proteins come from another species
*It can spread across the planet, driving other strains extinct –> flu pandemic
*Flu researchers are predicting that influenza viruses will jump from wild birds to humans.
*Discuss with the person next to you: How might you go about predicting which mutations the next pandemic influenza strain might have? (5 mins)
Antibiotic resistance
*In the mid 20thcentury, scientists uncovered that bacteria produce compounds that kill other bacteria, including pathogens-> antibiotics
*Not long after the introduction of antibiotics, doctors started to observe instances when they failed.
*Antibiotic resistance has become more widespread over the years. Today, some bacterial strains are resistant to multiple antibiotics e.g. MRSA
Bacteria have developed resistance to antibiotics through evolution
*Bacteria have developed resistance to antibiotics through evolution.
*We have changed their environment by introducing lethalchemicals.
*Bacteria with mutations that protect them against this threat have been able to survive and reproduce, and their mutations have become more frequent in the population -> spread of antibiotic resistance
*This can happen within a single person
*If a new resistance gene arises in one bacterial lineage, it can jump to another lineage –> horizontal gene transfer.
*Groupsof resistance genes, known as cassettes, can also jump from one bacterium to another
*“Based on scenarios of rising drug resistance for six pathogens to 2050, we estimated that unless action is taken, the burden of deaths from AMR could balloon to 10 million lives each year by 2050” (AMR Review, 2016)
*Discuss with the person next to you: What are some different ways we may be able to start to tackle antibiotic resistance? (5 min)
