[alexholehouse]

This is oddly poignant to me. I just (literally a few hours ago) submitted my PhD thesis on (broadly) the biophysics of emergent phenomena. People don't usually read theses cover to cover, with good reason, but I included one short paragraph in the preface to be the true "take home" message:

We wish to understand mechanism through the elucidation of design principles, yet evolution does not select for principles, it selects for fitness, an epistatic and emergent property. If similar outcomes can be achieved in different but equivalently fit ways, then given the stochastic nature of evolution this is almost guaranteed to happen. We have specific examples where every statement in the preceding paragraph is true [ed: a collection of proposed mechanisms]. We do not need one person to be right or wrong; our nascent understanding of complex biological systems is that the space of information-processing solutions is astronomical. Think of the diversity observed in structural biology - the repertoire of tertiary structures is enormous. There are countless examples of nearly identical functions being performed by proteins with radically different structure.

This divergence, this variety in structure and function, is what makes evolution robust. It is an inherent bet-hedging mechanism woven into the fabric of statistical physics. On the contrary, the desire to categories and abstract complexity into distinct groups is an inherently human endeavour. Much as we may wish and as convenient as it would be, Nature does not have a plan.

[latently]

Is fitness emergent, or fundamental? If you didn't discuss this, you should add another year to your PhD!

[SamBam]

"Fitness" is simply the name we give to the likelihood that an organism will have multiple generations of descendants.

This value of likelihood is an emergent phenomenon given an environment and an organism.

[latently]

That's not deep enough for my tastes.

[irickt]

Is your work available to read?

[alexholehouse]

The thesis won't be publicly available for a while because there is fair amount of (currently) unpublished data that is associated with various collaborations.

[dtornabene]

+1 as well, very very interested. If you could post some resources that an interested reader could educate themselves with in the meantime, it would be deeply appreciated. Maybe a sample of the bibliography from your thesis?

[alexholehouse]

So for some context, my work is not directly about evolution, but about how amino acid sequence determines function in the context of unfolded/disordered proteins.

That said, here are several at least semi-relevant papers that have influenced my thinking on a bunch of things (no particular order).

[1] Wheeler, L.C., Lim, S.A., Marqusee, S., and Harms, M.J. (2016). The thermostability and specificity of ancient proteins. Curr. Opin. Struct. Biol. 38, 37–43. (Probably paywalled but available on the Harms' lab website - https://harmslab.uoregon.edu/publications/. Mike's work on thinking about the biophysics of evolution is in general super cool. Similarly work by Adrian Serohijos is really interesting, although I am in general less familiar with it http://www.serohijoslab.org/publications.html)

[2] Tikhonov, M. (2016). Community-level cohesion without cooperation. Elife 5. (Open Access, really cool, and publishing a single-author original paper in a top journal in this day-and-age is incredibly impressive).

[3] Riback, J.A., Katanski, C.D., Kear-Scott, J.L., Pilipenko, E.V., Rojek, A.E., Sosnick, T.R., and Drummond, D.A. (2017). Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response. Cell 168, 1028–1040.e19. (Paywalled, but IMO a HUGELY important study for thinking about 'aggregation' in the context of cellular fitness)

[4] Chakrabortee, S., Byers, J.S., Jones, S., Garcia, D.M., Bhullar, B., Chang, A., She, R., Lee, L., Fremin, B., Lindquist, S., et al. (2016). Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits. Cell 167, 369–381.e12. (Paywalled, but potentially one of the most important discoveries in cellular adaptation in decades. More work to be done though!)

[5] Halabi, N., Rivoire, O., Leibler, S., and Ranganathan, R. (2009). Protein sectors: evolutionary units of three-dimensional structure. Cell 138, 774–786. (Paywalled, but super important for thinking about the relationship between local structural coupling and evolutionary behaviour. In general, everything Rama puts out is just gold.)

[TheOtherHobbes]

+1 - I'd like to see a copy too.

[henry_bone]

You've submitted this. I hope the spelling and grammatical errors aren't a problem for the readers. First of which is a missing 'the' in the first sentence. Later 'categories' instead of categorise.

Still, it seems interesting and I wish you all the best. I hope you are awarded your PhD.

[alexholehouse]

Thank you - categories vs. categorise is a great spot!!! Where are the spelling mistakes? I don't see the missing 'the' in the first sentence? Mechanism here is in the abstract, if that's what you're referring to? That said, I've also not slept a lot in the last week...

FWIW, this is the submission to my committee, so I'm now spending the next few weeks meticulously going through to tighten up the grammar, catch typos etc., before it gets officially submitted in June.

[jfaucett]

Yes. I think he meant

"We wish to understand mechanism through "

should have been

"We wish to understand the mechanism through "

I had to pause on that spot too because it felt stilted when reading over it, though after reading it again I got what you were talking about and it read fine.

[anentropic]

> but equivalently fit ways, then given the stochastic nature of evolution this is almost guaranteed to happen

I would probably put different commas:

"but equivalently fit ways then, given the stochastic nature of evolution, this is almost guaranteed to happen"

I suggest this based on intuition alone, but I believe the principle is: http://www.grammar-monster.com/lessons/commas_for_parenthesi...

[henry_bone]

My bad on the missing 'the'. Mechanism is in the abstract. Of course it is. I see it now. Sorry about that.

Probably wise to mention your PhD here on HN. Nerds (apart from me) are the finest proof readers and grammar checkers the world has ever seen.

Seriously, all the best on your PhD submission. Sorry for the confusion.

[alexholehouse]

Not at all - there's some additional text that provides set-up for the idea of mechanism. Re-reading it now cold, I read it exactly as you (and others) did as well. And I (embarrassingly) am relatively confident I wouldn't have caught the categories/categorise error, huge thank you!

[fnord123]

> the desire to categories and abstract complexity

categorize

(Please don't kill me)

[teekert]

Haha, man first time I opened my thesis, all fresh from the press, on a random page I saw an error. PhD students don't have editors haha, only professors who probably don't read back to back.

[fiatjaf]

I don't understand how a huge collection of evidences of emergent phenomena proves that Nature does not have a plan.

[mannykannot]

It is unprovable, because you can always posit a plan that matches the actual outcome from what was actually a random process. What the evidence does do is to weaken the claim that there is evidence for a plan.

[meric]

The plan is clearly to do anything to live and reproduce...You can see the innate struggle against increasing entropy in most living things, even as death is certain, because certainty is death.

[boomboomsubban]

This isn't proof of a plan, life does anything to live and reproduce because life without those qualities would not be sustainable. Those traits could be accidental though. The plan also isn't consistent when you step back, everything from planets to the universe do not seem to be following this plan.

[meric]

Nature produce plans - nature produced you and you have plans...And if you have plans it's not too much of a stretch to say other living things have plans too, and their degree of planning varies depending on their level consciousness, memory and intelligence. The detail of planning is a continuum between non-life, virus, microbes, plants, animals, and humans. The intention in planning, however, is mostly constant.

[boomboomsubban]

Or both nature and me produce no plans, our actions are the result of some set of variables that have led to this point. This isn't proof.

And you're still focusing on too narrow of a spectrum, you can't even be sure that life must follow these rules just that it has in the one example we have.

[devoply]

Nature has a plan, it's called extinction. What is it over 90% of things which ever evolved have gone extinct. That's nature's plan to make things which are very, very, very likely to go extinct. Some may say that's it's a sieve, but if it's a sieve then why is the universe not filled with intelligent life, it's not a sieve, it's a death sentence. We're all made to die, eventually forever. Into the deep, dark night. All of us.