A term coined by Michael Behe: Irreducible Complexity Irreducible complexity is just a fancy phrase I use to mean a single system which is composed of several interacting parts, and where the removal of any one Alan R. Rogers of the parts causes the system to cease functioning. (Behe, 1996) Now widely used to argue that evolution cannot account for April 7, 2015 complex adaptations.

1 / 30 2 / 30 Outline Not a new idea

“The entirety of an organic being forms a coordinated whole, a unique and closed I History of irreducible complexity system, in which the parts

I Bacterial flagellum mutually correspond and work together in the same specific I Blood clotting cascade action through a reciprocal relationship. None of these parts can change without the others changing as well.” (Cuvier, 1831, p 59)

3 / 30 4 / 30

Charles Darwin Charles Darwin “We should be extremely “If it could be cautious in concluding demonstrated that any that an organ could not complex organ existed, have been formed by which could not possibly transitional gradations of have been formed by some kind.” (Darwin, numerous, successive, 1859) slight modifications, my Went on to explain, with theory would absolutely examples, how selection break down.” (Darwin, can construct organs 1859) with irreducible complexity.

5 / 30 6 / 30 We now know that Pritchard was wrong Charles Pritchard (1866)

First to argue that vertebrate eye could not plausibly evolve. The eye evolved gradually, by individually-adaptive steps.

Change in any part Selection can construct irreducible complexity. requires simultaneous delicate adjustments in Pritchard’s argument was just a failure of imagination. all other parts.

Not plausible that this could happen by natural selection.

7 / 30 8 / 30 Michael Behe An underlying assumption Coined term “irreducible complexity.”

Knows that irreducible complexity can evolve: Demonstration that a ”as the complexity of an system is irreducibly interacting system increases, complex is not a proof that the likelihood of such an there is absolutely no indirect route drops gradual route to its precipitously.” (Behe, 1996) production. Although an irreducibly complex system can’t be produced directly, Sounds plausible, but is it true? one can’t definitively rule out the possibility of an indirect, circuitous route. (Behe, 1996)

9 / 30 10 / 30 Outline Bacterial flagellum

About 30 proteins

“Because the bacterial flagellum is necessarily History of irreducible complexity ◦ composed of at least I Bacterial flagellum three parts—a paddle, a I Blood clotting cascade rotor, and a motor—it is irreducibly complex. Gradual evolution of the flagellum. . . faces mammoth hurdles” (Behe, DBB, p. 72) (Yonekura et al 2000)

11 / 30 12 / 30 Homologies with type-III secretory system Type-III Secretory System Gray shows proteins homologous between Cellular hypodermic bacterial flagellum and syringe type-III secretory system.

Used by some bacteria A subset of flagellar (including bubonic proteins has a function plague) to inject toxins unlike that of flagellum. into cells of host. (Hueck 1998) Flagellum not irreducibly complex. (Miller 2004)

13 / 30 14 / 30 Outline How blood doesn’t clot

I Fibrinogen, a protein in blood, has a sticky portion. History of irreducible complexity ◦ I Sticky piece usually covered by molecules with negative Bacterial flagellum charge. ◦ I Blood clotting cascade I These repel, so fibrinogen molecules don’t stick together.

I Blood flows freely through circulatory system.

15 / 30 16 / 30 How blood clots

Blood clotting 1. An enzyme, thrombin, cuts the covers off of fibrinogen pathway molecules, which then stick together as clots. 2. Thrombin is usually inactive—activation requires another At each step, number of enzyme, called Factor X. molecules is multiplied by 20 or 30 . Total 3. Factor X works only if activated either by Factor VII or × × Factor IX. amplification exceeds a million fold. 4. And so on, as shown in next slide.

(Miller & Levine)

17 / 30 18 / 30 Can such a system evolve? Is the clotting system irreducibly complex?

I Hemophilia A: mutational damage to clotting factor VIII.

I Hemophilia B: mutational damage to clotting factor IX. “The blood clotting system fits the definition of irreducible I Mild cases result from mutations that reduce activity of complexity. That is, it is a single system composed of several protein. interacting parts that contribute to the basic function, and I Life expectancy: 11 y for severe untreated cases. where the removal of any one of the parts causes the system to cease functioning.” (Behe, 1996, Darwin’s Black Box, p. 86)

I Animals with low blood pressure don’t need clotting systems.

I Many insects don’t have them.

19 / 30 20 / 30 600 my ago, a small ancestral pre-vertebrate with a A small improvement low-pressure circulatory system Arrange for an inert protease to circulate in the blood all the time.

I Pancreas makes proteases used in digestion. Most are

I Would have had white blood cells, which are sticky and inactive until a piece is snipped off by another protease. tend to plug leaks. I Duplicate a protease gene and mutate its on/off switch so

I For internal signalling, each cell would have had it is turned on in liver. Gets inert protease into circulatory proteases—enzymes that cut proteins. system.

I When a cell breaks, proteases are dumped into circulation I When cells break, the proteases within them activate this and begin chopping up protein. new one, which chops up other proteins.

I Some broken proteins are less sticky, some are more sticky. I Some of the resulting pieces are sticky and clot.

I The sticky ones would clump and plug leaks. This improves clotting by multiplying the activity of proteases internal to each cell. All this reduces bleeding in animals without clotting systems. Still relies on fact that some chopped up protein pieces are sticky. 21 / 30 22 / 30

Initial clotting A duplicates to form pathway B TF (tissue factor) is a TF activates both A and protease inside cells. B. A is the inert form of our A∗ and B∗ both activate circulating protease. fibrinogen.

A∗ is the active form. A∗ and B∗ weakly activate A and B. A∗ also (weakly) activates other copies of No harm, no A. (A and TF are both ∗ improvement. proteases.)

23 / 30 24 / 30 Allow the two Prediction: clotting proteins should have similar proteases to amino-acid sequences specialize

B mutates, becoming less likely to cut fibrinogen but more likely to cut A. I Evolved from a single ancestral protein. A no longer needs I Different species show the same phylogenetic relationship sensitivity to TF. among clotting proteins.

Favored by selection, because two-stage system accelerates clotting.

25 / 30 26 / 30

Puffer fish

Clotting cascade lacks 3 of components found in Relationships human cascade. among clotting proteins Works fine. Clotting cascade not irreducibly complex.

(Jiang & Doolittle 2003)

27 / 30 28 / 30 Summary Sea squirt

A chordate, but not a I The idea of irreducible complexity goes back to Cuvier. vertebrate. I Refuted by Darwin.

I Type-III secretory system demonstrates that bacterial No clotting system. flagellum isn’t irreducibly complex. Yet has a fibrinogen-like I There is a plausible sequence of adaptive evolutionary protein. steps for the blot clotting cascade. I Phylogeny supports this evolutionary hypothesis. Fibrinogen has evolved a I Puffer fish proves that the cascade isn’t irreducibly different function. complex.

29 / 30 30 / 30