Mutations create functional information and mutations are chemical processes. Ever heard of keto-enol tautomerization? What about cytosine deamination? Those are the sort of chemical events that lead to mutations which could eventually generate novel functions.
5 posts were merged into an existing topic: SCD’s Questions about Sponge Genomes
@colewd Please restrict the LUCA discussion to the other thread. It is off topic here.
This is right there are 40 sequences whose expression needs to be coordinated to build the motor. The total number of nucleotides amount the 40 genes is about 100k.
The papers that challenge Behe’s work use historical sequence comparison to build their hypothesis. If her students are knowledgable about functional information they will know this is a superficial explanation.
I agree with you here.
How do you navigate the search space? What mechanism directs a sequence of 4^100000 possible arrangements to find a working solution for mobility?
How would you test if the mechanism is capable of this?
It is you who is incorrect, for wild-type pfcrt seem to have CQ-transport activity.
Natural selection can help navigate that search space.
The flagella has many parts and there is no single sequence that forms all those parts. This makes your second question wrong in the first place.
It seems you skipped this part in the paper you cited:
So who is incorrect now? Next time don’t be in hurry to cite papers you haven’t read.
How would it do this? The Lenski experiment had 75 mutations fixed after 60000 generations. The total search space is 100k if you add up all the genes required.
No, I don’t think I’m wrong. To see why, one has to remember the definition of FI for a given function. We have FI=–log2 of the ratio Target space/Search space. And since for a given environment, both the numerator and denominator are what they are, i.e. invariant, FI is also invariant.
What is “x” in Hazen’s equation?
x (e.g., a folded RNA sequence that binds to GTP)
Do you really mean to say that an RNA/DNA sequence cannot change? This is what you are implying.
[quote=“Michael_Okoko, post:12, topic:14185, full:true”]
You are incorrect and you are the one who didn’t read the paper. Here is a relevant passage supporting the CQ transport activity of PfCRT3D7, the wild-type version of the protein:
Next, we investigated the mechanisms underlying the different responses between CQ-sensitive and CQ-resistant PfCRTs in cis -inhibition. We focused on CQ uptake by PfCRTs because oocytes of Xenopus laevis expressing resistant PfCRTDd2 were reported to take up CQ, whereas oocytes expressing CQ-sensitive PfCRT3D7 did not (16). In reconstituted liposomes, CQ-sensitive PfCRT3D7 showed significant uptake of CQ (Fig. 3 A and B ). However, CQ-resistant PfCRTs exhibited an increase in CQ transport activity in accordance with the degree of resistance, with that in PfCRTDd2 showing a threefold increase (Fig. 3 A ). Kinetic analysis of CQ uptake indicated that the increase in activity was due to a decrease in affinity to CQ (increase in K m value) and an increase in the V max of the transporter (Fig. 3 B and C ). Thus, the lack of an effect of CQ on TEA uptake in CQ-resistant PfCRTs was due to changes in kinetic properties. This implies that CQ is discharged from DV by PfCRT even in CQ-sensitive malaria parasites and that the amount of CQ discharged from DV is significantly increased in CQ-resistant variants.
By pushing evolution through a network of functional protein sequences.
How is this relevant to the present discussion?
At that rate it would take ~27 thousand years to fix 100k mutations. A geological blink of an eye.
Of course, we don’t really need to evolve de novo genes for the flagellum proteins, as basically all of them are homologoues derived from other protein coding genes, and we even know of examples where multiple useful functions can co-exist in the same protein coding gene. The flagellin can also function as an adhesin, just to pick an example.
Nope. Both point mutations in, and copy number changes of the gene pfmdr1 also increase chloroquine resistance, they just don’t give as high resistance as PfCRT mutations. They do however also work synergistically with PfCRT mutations.
There is even some evidence that mutations in a 3rd gene, pfmrp, also contributes to CQ resistance.
A mere matter of decades.
So evolving resistance in decades is not impressive to you. Okay. I’m sure evolutionary biology will collapse under the realization that a parasite is currently only known to have evolved resistance to a novel drug through mutations and selection on at least three different genes, in a matter of decades.
It’s weird how this is even possible, given how often we’re told natural selection is powerless to do anything but weakly slow down the inevitable fitness decline to extinction.
Edit: Re-posting because I accidentally replied to wrong person.
The Lenski experiment was designed to limit evolution, not encourage it.
Gil, you really should not be doing textual analysis of passages; it just shows your lack of understanding. Data support conclusions, not anyone’s words.
That experiment in the cited and (even linked) paper used Xenopus oocytes. It also had a much better negative control, oocytes expressing no RfCRT at all:
Note that there is no difference at all between the open circles (negative control uninjected oocytes) and the wild-type PfCQR (triangles) in panel A.
So, which is a more physiologically-relevant system? Live oocytes, or nonliving liposomes? Which experiment has a better negative control?
The data clearly show that you’re wrong.
But wrong or right on this matter, now that you know that Behe’s claim about chloroquine resistance needing two simultaneous mutations is dead wrong, are you going to recommend that he retract and/or correct that part of the book as his translator?
Reading papers involves much more than reading the text.
3D7 is not “the wild-type version” of PfCRT. it is one among several wild-type strains.
Its strange you say I am incorrect when the quote I made from the paper you cited contained citations to several papers all of which show that wild-type strains of PfCRT do not facilitate CQ uptake.
That said let’s look at your quote from the paper you cited.
The authors of this paper used liposome-embedded PfCRTs for their CQ uptake analysis, whereas in Summer’s et al, and other papers I have read, PfCRT was expressed in the membranes of oocytes of Xenopus laevis. I don’t need to tell you that these oocytes are a better experimental model system for this sort of investigation.
This, I presume, is where you think you found support for the CQ uptake by wild-type 3D7.
Its a strange result since it appears to conflict with other published papers on the subject. In other studies, the absence of the mutations (especially K167T) found in resistant strains prevents wild-type strains like 3D7 and HB3 from transporting CQ. In Summer’s et al (2014), the WT strain was HB3 and it clearly showed no activity. In Martin et al. (2011), which your paper cites, D10 was the WT strain used and it failed to take up CQ as well. I think this finding is wrong.
We knew PfCRT was the culprit protein for CQ resistance based on a genetic cross between HB3 and Dhd2 (a resistant mutant). That genetic cross allowed researchers spot about 8 substitutions that were absent in HB3, but now present in the PfCRT of its progeny which allowed those progeny to develop resistance to CQ. HB3, 3D7, D10 all lack those PfCRT substitutions, including the minimal ones. You can see this in the table below:
Based on sequence data, 3D7 like HB3 should not be able to take up CQ and that’s what is observed in every other study I have looked at on the topic.
In any case, the weight of evidence lies in favor of wild-type PfCRTs not having CQ-transport activity and the acquisition of that activity following substitutions to identified residues in several parts of the protein.
A crucial point I omitted! Thanks.
Of course a RNA/DNA sequence can change. But that doesn’t mean that the FI associated with a given level of function of a given system in a given environment can change. Let’s take the example of RNA sequence. Let’s define the function as the ability for RNA sequences of a given length n to bind ATP with an affinity above a given threshold. In this system, the target space (the number of RNA sequences of length n having the defined function) is what it is, ie., is invariant. Same thing for the sequence space. It follows that the FI associated with the defined function is also invariant.