BIO 202 — Lesson 30: When cells stop competing

Your body is a bee colony. The gametes reproduce. The somatic cells — muscle, skin, gut, neurons — help the gametes survive. All your cells are 100% related to each other. Each gamete is fully related to each other cell in your body. What your body is, is basically a bee colony. We have self-divided roles. Multicellularity is just kin selection on cells. Same math. — 461_lec29_02

A — Free-living unicellular null

A population of independent cells. Each reproduces for itself. Cell-level cov(w, z) is the only thing in the equation. There is no body. Named null: cells are the unit.

You are not the pond water you looked at in the microscopy lab. In pond water, what were those little cells doing to each other? Murdering. They were murderers trying to kill each other. Your cells don't do that, normally. As a result, they can cooperate with one another. They can have something to push against. They can build extracellular matrix. The fibronectins and integrins are how a cell anchors and pushes — because in you, things stay still long enough for that to work. — 145_lec09_05

TODO: free-living-cell sim. Cell-level Price ratio; show no group structure.

B — Add the colony: germ and soma

Cells aggregate into colonies. Some specialize as germ (reproductive); others as soma (non-reproductive support). Within-colony cov(w, z) at the cell level competes with between-colony cov(W, Z) at the colony level. Slide the relatedness between cells in a colony (r) and watch which term dominates.

Your neurons cooperate because they're nearly genetically identical. The cost to a neuron to help another nearly identical, almost perfectly related neuron isn't actually a cost — genetically speaking. They're basically the same. That's why thought is possible — your neurons aren't trying to destroy each other. — 202_lec30_03

Move the within-colony relatedness slider. 200 cells, 10 colonies of 20. Each cell has a "selfish growth" trait z and a fitness w. As cells become more related within a colony, between-colony cov(W, Z) takes over from within-colony cov(w, z).

within-colony cov(w,z): — | between-colony cov(W,Z): — | total cov: —

which level is the unit? —

within-colony relatedness r = 0.50 selection on the colony (b) = 0.50 seed = 42

Red points: each colony's (Z, W) — the between-level data. Gray: individual cells' (z, w) within colonies. When the red point cloud is more correlated than the gray, the colony is the unit and the cells are parts. When the gray correlation dominates, the cells are still in business for themselves.

C — The diagnostic: when is the colony the unit?

Run the Price ratio from Lesson 26 on this two-level system. When the between-colony cov exceeds the within-colony cov, the colony is the unit. When it doesn't, you have a population of cooperating-but-still-cellular agents. The diagnostic answers "is this an individual yet?"

A big part of being a multicellular organism — kind of the definition — is that your cells are not growing as much as they could. For the betterment of all the other cells. All your cells are choosing to make fewer copies of themselves individually than they could, in order for the organism as a whole to work. This is a really difficult and problematic thing for a cell to do, because if you make more of yourself, you become more common — no matter why you're making more of yourself. Which is how you get cancer. — 145_lec22_04

The diagnostic is just the ratio cov_between / (cov_within + cov_between) — the same between/total quantity you computed as F_ST in Lesson 14, now applied to a fitness covariance instead of an allele frequency. Same machine, new level. Diagnose four real systems:

Honeybee workers. Within-colony cov(worker reproduction, fitness) ≈ 0 (workers don't reproduce). Between-colony cov(colony productivity, colony survival) is large. Ratio ≈ 1: the colony is the unit.
Your soma. Within-body cov(cell-level z, cell-level w) ≈ 0 (cells don't compete with each other for reproductive turns). Between-body cov(somatic phenotype, fertility) is the entire story. Ratio ≈ 1: the body is the unit.
Volvox. Some cells are sterile, some reproduce. Between-colony cov dominates by a factor of ~10. Ratio ≈ 0.9: the colony is the unit, with measurable but small within-colony slack.
Cancer. A somatic-cell lineage that has re-evolved its own cov(z, w). Within-body cov re-emerges. Ratio drops sharply: the body's "individuality" is failing.

D — Three empirical anchors

(1) Honeybee colonies: between-colony cov for productivity exceeds within-colony cov for worker reproduction. The colony is the unit. (2) Volvox: somatic cells are sterile but increase colony fitness — the cleanest unicellular-to-multicellular transition that's still visible today. (3) Cancer: TCGA-style somatic-mutation timecourses showing the within-body cov re-emerging. The same diagnostic catches the failure mode.

You can only inherit cooperation, because cooperation is the thing that persists. The lineages whose cells fought each other into oblivion didn't make it. But your body is de novo inventing ways to try to break you down. That's cancer, that's disease, that's ailment. We constantly inherit the framework of cells working together. But the cells inside us are constantly inventing new ways to defect. — 202_lec30_05

TODO: three anchors. Honeybee or Volvox dataset for the cleanest cooperative case; TCGA somatic mutation timecourse for the failure mode; .R export. Non-trivial code mod: write a generic cov-ratio function that takes any (w_i, z_i, group_id) table and returns the diagnostic. This is the cross-arc deliverable referenced in PROJECT_PLAN §7.6.