Applied Evolution

roughly how many people have soil-transmitted helminth infections

over 1 billion

what is the life cycle of Haemonchus contortus (barber pole worm)

-eggs secreted out of sheep in feces

-3 larval stages occur in soil

-last larval stage migrates to grass

-grass and larvae eaten by adult sheep

what does the barber pole worm infect

small ruminants

what are symptoms of barber pole worm infection

anaemia, lethargy, weight loss, death

what about the barber pole worm makes it a good animal to study

drug resistance is very common and includes all major classes of antihelminthics

how many classes of anithelminthics are there

5

why is this an issue for humans as well (one health issue)

same few classes of antihelminthics are used in humans, resistance in animals could spread to humans

why does anitmicrobial reistance evolve so rapidly

-high mutation rate

-short generation times

-very large and already viable population

-strong selection pressure

-few classes of drugs

-frequent mis-use

-resistance genes alreay present in pathogen populations due to sourcing of drugs from nature

what caused the increase in resistance of leishmaniasis in north india in 2000

-antimony containing drug used to treat leishmaniasis

-shallow wells contained high levels of arsenic opened in 1970

-leishmania got into wells and adapted to arsenic levels

-arsenic's close chemical relatedness allowed arsenic resistant leishmania to resist antimony drugs

how can we slow or avoid reistance

- antimicrobial drug combinations

- anti-resistance drug combinations

-alternatices to antimicrobials

-reversion to sensitivity (no good evidence in worms)

-In cancers use adaptive therapy, leave some sensitive tumour cells alive to compete with resistant cells

-refugia, keep some worm populations unexposed to drug to reduce selection pressure

how can genetic methods help fight resistance

allows detection of resistance a lot faster,

in worms allows species identification,

allows tracking of evolution and spread of genes

how do we diagnose helminth infections

FECRT test. checking for helminth cysts in poop

what are the 4 mechanisms of resistance

-Reduced sensitivity to drug

-Reduced uptake of drug

-Removal of drug

-Inactivation of drug

what is the only recommended treatment for malaria

ACTs

why does malaria have such a huge capacity to adapt

huge numbers of parasites, combined with hundreds of millions of cases every year and a high mutation rate means that every possible variant of malaria is 'tried' multiple times a year in africa

what are ACTs

fast acting but short lived Artemisinin combined with a longer acting drug that completely clears the disease

what gene is responsible for ACT resistance seen in cambodia and much of southeast asia

kelch13

what are the 5 reasons why is southeast asia seeing a rise in ACT resistance

-issues with quality and counterfeit drugs

-incorrect dosing

-artemisinin used on its own without combo

-combo of low transmission and forest dwelling mosquitos

-haplotype pre-adapted to resistance

what is evolutionary medicine

applying evolution to understand how and why diseases occur

what is the mutant model approach

using mutant model organisms (either induced mutations or screened for mutants) to study diseases

what are 4 limitations of the mutant model approach

-limits science to answers only these organism can provide

-model organisms chosen due to simplicity in presence (either disease shows or not) whereas a lot of diseases are gradients

-low environmental input

-Inbred models dont reflect natural genetic diversity

what is the evolutionary mutant model approach

finding organisms in the wild that have mutations/adaptations relevant to human diseases

what are some advantages of the evolutionary mutant model approach over the standard mutant model approach

-adaptations are screened by natural selection rather than researchers so we know these mutations work

-adaptations are in wild populations so are subjected to environmental variation

-higher genetic variation

which human diseases are Antarctic Icefish used to study

Anaemia and ostopoenia

what gene was found in icefish that is critical in human red blood cell development

bloodthirsty (bty)

How was the bty's gene critical role in rbc development proved

-full genome scan found bty gene in relatives of icefish that make haemoglobin

-deactivation and reactivation (aka knockdown and rescue) of bty gene in zebrafish proved its role

what is the evolutionary reason that icefish have ostopoenia

-orignally lost swim bladder to live as benthic fish

-pelagic competition left

-recolonised pelagic zone with increased buoyancy from less dense bones and increased fat

which human disease are Mexican cavefish used to study

Retinal degeneration

how were cavefish used to study retinal degeneration

-mexican tetra has both surface and cave dwelling version

-genomes of both version compared

-gene pax6 identified as a difference

-this gene in humans causes malformation of the iris

which human diseases are African cichlids used to study

craniofacial malformation diseases (hypo, hyper and macrodontia)

why are cichlids a good study group

huge diversity of species with incredibly similar genetics, making it easier to discern mutated genes

How do we find out what genes correspond to a certain phenotype

genetic mapping (multivariate glm)