Another Rad Day
Breakfast was well made eggs and great company with a sharp-minded person who was NOT a scientist and made lecherous British noises at me.
Then I went to my cube and finished my presentation on evolution of bacteria.
Just my lab's weekly meeting, I had nominated myself for journal club because I was sick of coding.
The paper was a review of some radical early (1990) thought on evolution in pathogenic organisms.
Here's the scoop:
People think virulence is a primitive state and that the evolutionary path of a pathogen is towards commensality. Because when you have a parasite-host relationship, where's the balance going to land eh?
Either the host kicks it.
Or the parasite gives up.
OR the host learns to tolerate what has become your friendly neighborhood commensal.
here's the formula:
Ro = reproductive rate (aka Darwinian fitness*)
B = rate of transmission
N = number of susceptible hosts
a = rate of death from infection
b = rate of death from other causes
v = recovery/clearance rate
1 infectious individual produces BN secondary infections
Persistence = reciprocal of rate of removal = 1/(a+b+v)
Ro = reproductive rate = transmission x persistence
Ro = BN /(a+b+v)
Now if you were a bacteria and wanted to be patrissimo and make as many babies as possible, what would you do? You'd fucking increase your rate of transmission, move in everywhere, stop hurting your host, maybe even start helping your host, and never ever LEAVE.
Looking at the equation above, it seems obvious that commensality is *the* route. There are plenty of observations to support this idea. There are a lot of bacteria that seem to attenuate. HIV seems to have. Our own beloved gonorrhea seems to have over the last few decades even. It seems that when a parasite jumps from environment (or a host) to new species, it takes a bit of time to learn to tolerate each other. This seems to be the case in some, maybe most bacteria
BUT BUT BUT
when you look at the tree of Neisseria, you see that the pathogens are one sister clade on the tip of a big tree of commensals. The principal of parsimony would have us believe that pathogenicity arose once in the ancestor of gonorrhoeae and meningitidis, rather than lost multiple times in multiple lineages. And parsimony *is* an assumption, but it's often a good one.
So how the fuck is that possible?! There's nothing to indicate this species has undergone a profound change of environment. It lives on human! Didn't jump from the water. Didn't jump from a monkey. Is it possible that it became... or is becoming virulent?
Let's get back to the bloody equation eh? When we maximized our reproductive rate up there we assumed that increasing your rate of transmission, moving in everywhere, stopping hurting your host, maybe even starting to help your host, and never ever LEAVEing are independent.
Well, what if they're not. Hmmmm?
What if there are trade-offs eh? What if increased transmissibility leads to increased virulence as a side effect. Maybe the trade-off for being a little more social is that you accidently get carried away once in a while, eh? This is what seems to happen in both meningitidis and gonorrhoeae. Ususally nothin' happens. Once in a while... somethin. WHY?!
Maybe because it can. Maybe stuff doesn't go to the equilibrium we expect, maybe it stops somewhere else and fills another statistical niche. Because it can. Because there's more than one stable strategy, even if some are more popular! It takes all kinds right?
Let's move away from theory for a sec. I'll tell you a little secret.
It's a little difficult to tell in some places because our genomes are still unfinished contigs (a little broken up), but there's one serious virulence gene, IgA protease that _was_ a recent insertion event. That's evidence. I bet we'll dig up some more.
I have more swirling in my head on the patterns of evolution in symbionts (mutualists, commensals, and parasites all). It's a big cloud, but it feels like it's condensing into something.
*what other kind is there eh?
Bottom line: I read a bunch, synthesized, and gave my mentor evidence to overthrow the paradigm she preached to us at last week's lab meeting.
It seemed to please her.
Then I squirmed and whined and chittered while my awesome brilliant tattooist iterated over my Mandelbrot sleeve.
And now, to bed.
I gots to get back on the command line tomorrow.
Then I went to my cube and finished my presentation on evolution of bacteria.
Just my lab's weekly meeting, I had nominated myself for journal club because I was sick of coding.
The paper was a review of some radical early (1990) thought on evolution in pathogenic organisms.
Here's the scoop:
People think virulence is a primitive state and that the evolutionary path of a pathogen is towards commensality. Because when you have a parasite-host relationship, where's the balance going to land eh?
Either the host kicks it.
Or the parasite gives up.
OR the host learns to tolerate what has become your friendly neighborhood commensal.
here's the formula:
Ro = reproductive rate (aka Darwinian fitness*)
B = rate of transmission
N = number of susceptible hosts
a = rate of death from infection
b = rate of death from other causes
v = recovery/clearance rate
1 infectious individual produces BN secondary infections
Persistence = reciprocal of rate of removal = 1/(a+b+v)
Ro = reproductive rate = transmission x persistence
Ro = BN /(a+b+v)
Now if you were a bacteria and wanted to be patrissimo and make as many babies as possible, what would you do? You'd fucking increase your rate of transmission, move in everywhere, stop hurting your host, maybe even start helping your host, and never ever LEAVE.
Looking at the equation above, it seems obvious that commensality is *the* route. There are plenty of observations to support this idea. There are a lot of bacteria that seem to attenuate. HIV seems to have. Our own beloved gonorrhea seems to have over the last few decades even. It seems that when a parasite jumps from environment (or a host) to new species, it takes a bit of time to learn to tolerate each other. This seems to be the case in some, maybe most bacteria
BUT BUT BUT
when you look at the tree of Neisseria, you see that the pathogens are one sister clade on the tip of a big tree of commensals. The principal of parsimony would have us believe that pathogenicity arose once in the ancestor of gonorrhoeae and meningitidis, rather than lost multiple times in multiple lineages. And parsimony *is* an assumption, but it's often a good one.
So how the fuck is that possible?! There's nothing to indicate this species has undergone a profound change of environment. It lives on human! Didn't jump from the water. Didn't jump from a monkey. Is it possible that it became... or is becoming virulent?
Let's get back to the bloody equation eh? When we maximized our reproductive rate up there we assumed that increasing your rate of transmission, moving in everywhere, stopping hurting your host, maybe even starting to help your host, and never ever LEAVEing are independent.
Well, what if they're not. Hmmmm?
What if there are trade-offs eh? What if increased transmissibility leads to increased virulence as a side effect. Maybe the trade-off for being a little more social is that you accidently get carried away once in a while, eh? This is what seems to happen in both meningitidis and gonorrhoeae. Ususally nothin' happens. Once in a while... somethin. WHY?!
Maybe because it can. Maybe stuff doesn't go to the equilibrium we expect, maybe it stops somewhere else and fills another statistical niche. Because it can. Because there's more than one stable strategy, even if some are more popular! It takes all kinds right?
Let's move away from theory for a sec. I'll tell you a little secret.
It's a little difficult to tell in some places because our genomes are still unfinished contigs (a little broken up), but there's one serious virulence gene, IgA protease that _was_ a recent insertion event. That's evidence. I bet we'll dig up some more.
I have more swirling in my head on the patterns of evolution in symbionts (mutualists, commensals, and parasites all). It's a big cloud, but it feels like it's condensing into something.
*what other kind is there eh?
Bottom line: I read a bunch, synthesized, and gave my mentor evidence to overthrow the paradigm she preached to us at last week's lab meeting.
It seemed to please her.
Then I squirmed and whined and chittered while my awesome brilliant tattooist iterated over my Mandelbrot sleeve.
And now, to bed.
I gots to get back on the command line tomorrow.