Wasp Ethanol Tolerance

scientist vignette

this work was led by Sofia Bouchebti with Eran Levin at Tel-Aviv university in Israel

species of this paper

oriental hornet

key take away #1 of target paper #3

the highly efficient ethanol metabolism in hornets is most likely due to a duplication of the alcohol dehydrogenase (ADH) gene

key take away #2 of target paper #3

wasps may benefit from the 2x higher energy content of ethanol compared to glucose, as well as from its antimicrobial properties when feeding on Carrion

key take away #3 of target paper #3

Yeasts benefit through dispersal to new sources of glucose

key take away #4 of target paper #3

AUD in humans may be partly explained by slow ADH enzymes

key take away #5 of target paper #3

while ADH CN and allelic variation may explain Hornet EtOH tolerance, humans have more copies of ADH and cannot tolerate 80% EtOH. what else?

vespa orientalis

a social wasp that naturally consumes ethanol

80%

the ethanol concentration Vespa orientalis can tolerate without negative effects

4%

the ethanol concentration most other organisms can tolerate without negative effects

13C1 labeled ethanol

ethanol labeled with 13C (a stable isotope that they can easily detect in exhaled CO2)

mutualistic relationship

benefits both the wasp and the yeast

AUD heritability

50%

how to survive enormous amounts of alcohol 1

alcohol dehydrogenase (ADH) catalyzes the conversion of ethanol into acetaldehyde

what accumulates making you feel bad after alcohol?

acetaldehyde

how to survive enormous amounts of alcohol 2

acetaldehyde dehydrogenase then converts acetaldehyde to acetyl CoA with co enzyme A

how to survive enormous amounts of alcohol 3

in most organisms, genetic variations of ethanol metabolizing enzymes such as ADH modulate the effects of alcohol, and thereby influence the amount of consumed alcohol

how to survive enormous amounts of alcohol 4

in humans, seven different ADH genes with several isoforms have been identified (these are referred to as ADH1 through ADH7)

how to survive enormous amounts of alcohol 5

their gene products vary largely for their respective enzyme activity (Km values for ethanol vary by a factor up to 5,000)

Km

michaelis menten kinetics; a differential equation describing the reaction rate v (rate of formation of product P, with concentration p) to a the concentration of the substrate A

how can greater EtOH metabolism be achieved ?

better enzymes or having more copies. Hornets have duplicates

what is a highly effective ethanol metabolism in hornets due to?

due to a duplication of the alcohol dehydrogenase (ADH) gene

mechanisms for gene duplication

unequal crossing over

transposons

whole genome duplication

unequal crossing over

happens during prophase one of meiosis. Chromosome arms overlap about once per chromosome arm (this is normal recombination). Sometimes, alignment is off and one chromosome gets a larger fragment form the cross over; and the other chromosome gets a smaller fragment

transposons

"jumping genes" that behave like RNA viruses; can copy and paste DNA from one place to another. Can copy whole gene sequences. Sometimes leads to pseudogenes.

whole genome duplication

polyploidy; produced by non disjunction during meiosis that leads to gamete with varying chromosomal compliments. Can lead to wholesale gene duplication.

what happened to hornets with chronic ethanol consumption?

chronic ethanol consumption at concentrations as high as 80% had little impact on hornet survival probability AND little impact on lifespan

what happened to honeybees?

they cannot hang with the suace

how do we know hornets metabolized ethanol?

13C1 labeled isotope collected in a vacuum sealed chamber breathed off with CO2

what may have PNAS editors have said ?

"cool behavioral study on ethanol tolerance and metabolism in oriental hornets but what is the mechanism?"

what did the researchers discover when referencing publicly available data bases?

tandem duplication events in other species

which transcript of the alcohol dehydrogenase gene was found ?

NADP+

only figure in the origin of species

darwin's early musings on phylogenies from his "notebook B" in 1838 to the only figure in the Origin of species (1859). remember that all phylogenies are hypotheses.

phylogeny

share derived traits identify monophyletic groups- sets of taxa that include an ancestor and all of its descendants

review sequence alignment

synteny

shared order of sequences or genes between orthologous or paralogous genes (or whole chromosomes in related species); used to identify similarities and differences between species, and to reconstruct ancestral genomes

Gap

graphical and computational necessity when aligning orthologous or paralogous gene sequences or chromosomes

carbon 13

a stable isotope of carbon with six protons and seven neutrons. Makes up about 1.1% of all natural carbon on earth.

what plays a key role in metabolizing majority of ingested ethanol in the liver ?

ADH2, also known as ADH1B

how many forms of ADH1B?

3

which is the slowest ADH1B?

ADH1B*1 is the slowest at metabolizing ethanol among these forms and is the most prevalent globally, except in many part of east asia

what is the most common isoform in east asia, and what is its rate of work ? what does this cause?

in countries of East Asia such as China and Japan, the most common isoform is ADH1B2 which metabolizes ethanol much faster than ADH1B1

as a result of this fast breakdown, acetaldehyde accumulates as the enzyme that breaks it down becomes saturated

acetaldehyde

a toxic intermediate metabolite that can lead to the so called alcohol flush reaction with facial flushing, nausea, headache, and an increased heart rate

what does the unpleasant reactions caused by acetaldehyde accumulation cause?

ADH1B*2 carries might be less inclined to consume large amounts of alcohol so it's considered a protective genetic factor for AUD

hit in genome wide association studies (GWASs)

it is remarkable that the gene variant ADH1B*2 is by far the most consistent hit in GWAS for AUD. If you have it, you likely drink less

what contributes to AUD?

genetic factors, heritability of 50% but not just one genes, spread across a large number of genes (its pleiotropic)