Larry Moran’s Exit Exam

Attached is Larry Moran’s exit exam for biochemistry and molecular biology. Exit Exam for Biochemistry.

I probably will not get a lot of these right on the first try, but it is a good learning experience. When I don’t know the answer, I can look it up, so this is a good chance to review important concepts.

I will provide answers I think Professor Moran wants students to give, and then I’ll provide my own answers which I think he might dock points for if he were grading. I always try to give the answer the professor is expecting even if I disagree. It shows that I am trying to understanding of what he was trying to teach. It’s not a confession of belief on my part.

For example:

21.How much of your genome is functional?

Answer I think Larry is expecting:

10%, because of the limits mutational load imposes on a genome the size of a human’s and their reproductive excess. But even the 10% number is likely high since the Muller Limit of 1 mutation/person/generation might allow even less than 10% function for the human genome.

My answer:

don’t know, neither does anyone else

Smart Arse Answer:

10% despite the fact ENCODE says 80% because ENCODE are a bunch of “ignoramuses, crooks generating piles of excrement” according to Dr. Moran’s colleague Dan Graur.

Some questions stumped me like:

3.Why can’t you have a lipid monolayer?

Eh? Doesn’t a micelle “layer” count as having a mono layer? Guess not.

I guess the answer is the hypdrophobic tails of the amphipathic phospholipids will generally tend to attach to each other, therefore such lipids are more likely to spontaneously form and remain in the bilayer configuration. But a micelle monolayer associates the hydrophobic tails too, doesn’t it?

micelle and bilayer

Another Question:

17.Why are the amino acids sequences of a typical enzyme different in mice and humans?

Answer I think Larry is expecting:

Enzymatic polymorphisms occur because in many cases differences in amino acids at certain locations (such as those outside the active site) do not require high specificity. Function can be sustained under a variety of different amino acids in certain positions, thus random mutations in the process of common descent with modification will generate polymorphisms in positions which do not affect enzymatic function.

My answer:

The polymorphisms can be due to different functional constraints such as those resulting from necessary DNA binding motifs and microRNA regulatory targets that result in non-synonymous amino acid differences, Also there are possible different functionally significant post-translationtional modifications that are amino acid specific which have not yet been detected due to the difficulty of actually measuring such modifications in all possible contexts.

Another question:

30.Why do eukaryotic genes have introns?

My textbook non-answer:

Prokaryotes have introns, but no spliceosomal introns like Eukaryotes, so I believe Dr. Moran is referring to spliceosomal introns. Honestly, I don’t recall I’ve ever gotten a good answer from evolutionists. I don’t think Lehninger even attempted an answer. Since I don’t have copy of Larry’s textbook, but only Lehninger’s, can I be excused until I can get a hold of Larry’s book? 🙂

My answer:

For multicellular eukaryotes, the introns allow more diversity in gene expression between cell types as they can act as parts of robotic arms in 3D space to position regulatory and transcriptional machinery onto genes. This can happen from introns in other gene in a cis or even trans chromosomal context. Because of histones, chromatin complexes that contain introns are also capable of information processing and storage allowing them to be manipulated according to their histone chemical state to do gene regulation in a 3D manner as shown here:

3d robot intron

For unicellular eukaryotes, I don’t have a good answer at this time (and neither do I think anyone else does), except God wanted to make other KINDS of Rube Goldberg machines.

The role of introns that are transcribed or excised is still not well understood. Primate specific Alus are indicated to use introns to make circular dsRNAs that appear important in alternative splicing. Until high throughput methods emerge to sequence proteomes in large scale and detect alternative splices, post translational modifications, glyco conjugation, etc. the role of introns may not be evident to the extent they may effect these (especially alternative splicing).

Papers on the function of introns have been published that list even more roles for introns.

But here is the rest of the exam. I’ll put some answers out in the comment section. Some answers will have to wait until after I finish this semester’s biochemistry evening class at the NIH. 🙂 Anyone else can weigh in with their answers.

1.Where do non-photosynthetic chemoautotrophs get their energy?
2.What is a typical Gibbs free energy change for a metabolic reaction inside a cell?
3.Why can’t you have a lipid monolayer?
4.Why is DNA supercoiled?
5.Which pathway evolved first; glycolysis or glucoenogenesis?
6.Why is methionine an essential amino acid in humans but glutamate is not?
7.Can humans fix carbon dioxide?
8.What are the end products of photosynthesis?
9.How do you create a protonmotive force?
10.How do some species survive without a citric acid cycle?
11.Why is some DNA replication discontinuous?
12.Why does E. coli need so many molecules of RNA polymerase?
13.Why is the ribosome so big and complex?
14.Why are there six codons for arginine but only one for tryptophan?
15.Why is Levinthal’s paradox not a paradox?
16.Why does DNA rich in G/C denature at a higher temperature than A/T-rich DNA?
17.Why are the amino acids sequences of a typical enzyme different in mice and humans?
18.If protein folding is spontaneous then why do cells need chaperones?
19.Why do acids like acetic acid and formic acid have different pKas?
20.Why did you need to learn about the Michaelis-Menten equation?
21.How much of your genome is functional?
22.Why is ATP not an effective allosteric regulator of enzyme activity?
23.What is flux?
24.Why isn’t it correct to say that ATP is an energy-rich compound?
25.What was the point of learning about reduction potentials?
26.Why are transcription and translation separated in eukaryotic cells?
27.Why did it take so long to evolve an oxygen evolving complex in photosynthesis?
28.Why is fat better than sugar for storing energy?
29.Why do we need cholesterol?
30.Why do eukaryotic genes have introns?
31.What’s the point of homologous recombination?
32.How can bacteria survive without mitochondria?

116 thoughts on “Larry Moran’s Exit Exam

  1. Btw Allan, I think this one is right up your alley: Genetic Codes with No Dedicated Stop Codon: Context-Dependent Translation Termination
    Estienne Carl Swart, Valentina Serra, Giulio Petroni, and Mariusz Nowacki

    Summary
    The prevailing view of the nuclear genetic code is that it is largely frozen and unambiguous. Flexibility in the nuclear genetic code has been demonstrated in ciliates that reassign standard stop codons to amino acids, resulting in seven variant genetic codes, including three previously undescribed ones reported here. Surprisingly, in two of these species, we find efficient translation of all 64 codons as standard amino acids and recognition of either one or all three stop codons. How, therefore, does the translation machinery interpret a “stop” codon? We provide evidence, based on ribosomal profiling and “stop” codon depletion shortly before coding sequence ends, that mRNA 3′ ends may contribute to distinguishing stop from sense in a context-dependent manner. We further propose that such context-dependent termination/readthrough suppression near transcript ends enables genetic code evolution.

  2. Allan Miller: It’s not necessarily the case that this indicates extracellular, nonenzymatic origins though. One would expect enzyme-catalysed reactions to follow the most thermodynamically favourable routes first, which happen to be those that can occur non-enzymatically.

    Can you elaborate? I’m not sure I see why one would expect that. Are you saying there’s a bias towards catalysis of more thermodynamically favorable reactions for spontaneously emerging catalytic polymers?

  3. Rumraket,

    Can you elaborate? I’m not sure I see why one would expect that. Are you saying there’s a bias towards catalysis of more thermodynamically favorable reactions for spontaneously emerging catalytic polymers?

    I’m saying, in very broad and handwavy terms, that ‘simple’ catalysis would be expected (maybe just by me!) to arise first – just bumping up the yield of a particular reaction, shoving the equilibrium a bit further right, that sort of thing. The things that would be amenable to such simple rate change would be those that are ‘spontaneous’, albeit at low yield, when uncatalysed.

    The more complex stuff would be expected to arise later, just ‘cos it’s harder – pathways where there is a significant activation energy to be overcome, or a more elaborate reaction sequence. Stuff that may not happen at all outside of cells.

  4. Allan Miller,
    Enzymes do not change the equilibrium of a reaction. They simply speed up the forward and reverse rates of the reaction making the reaction reach equilibrium faster.

    Also, the notion of “spontaneous ” can be easily misunderstood. Enzymes can speed up reactions that have negative standard Gibbs free energy changes as well as those that have positive standard Gibbs free energy changes. Inside the cell, the net effect of enzymes is to allow all reactions to reach equilibrium where ΔG = 0. This is why so many reactions can run in opposite directions depending on the supply of substrates and products.

    The standard Gibbs free energy change does not determine whether the reaction is “spontaneous” or not when it’s part of a pathway. Most pathways, including gluconeogenesis and glycolysis, contain reactions with a whole range of standard Gibbs free energy changes ranging from very positive to very negative.

  5. Larry Moran: This is why so many reactions can run in opposite directions depending on the supply of substrates and products.

    I remember this penny dropping as an undergraduate. Why doesn’t a reaction stop at equilibrium as it does in a test tube? Remove the products and no equilibrium.

  6. Alan,

    Why doesn’t a reaction stop at equilibrium as it does in a test tube?

    Even in vitro, equilibrium does not imply that a reaction has stopped.

  7. keiths,

    No indeed. In reality, the forward and reverse reactions are happening with equal frequency resulting in equilibrium. “Stopped” is shorthand.

  8. But by that usage, “stopped” applies both to equilibrium in vivo and in vitro. Why do you think there’s a difference?

  9. 20.Why did you need to learn about the Michaelis-Menten equation?

    The Michaelis-Menten equation relates the initial reaction velocity to the final reaction velocity for a given enzyme and substrate.

    Reworked forms of Machelis-Menten equation can be used to analyze bi-substrate reactions which will indicate if inhibition is competitive, uncompetitive, or mixed.

    This will help elucidate what part of the pure “normal” substrate binds to the enzyme and thus give us insight into the mechanism of enzymatic action.

    From a medical standpoint, this can sometimes lead to creating synthetic enzyme inhibitors.

    Finally, Maud Menten (1879-1960) looks kind of cute for a famous chemist and physician.

    Skloot portrays Menten as a petite dynamo of a woman who wore “Paris hats, blue dresses with stained-glass hues, and Buster Brown shoes.”[5] She drove a Model T Ford through the University of Pittsburgh area for some 32 years and enjoyed many adventurous and artistic hobbies. She played the clarinet, painted paintings worthy of art exhibitions,[1] climbed mountains, went on an Arctic expedition, and enjoyed astronomy. She also mastered several languages, including Russian, French, German, Italian, and at least one Native-American language.[5] Although Menten did most of her research in the United States, she retained her Canadian citizenship throughout her life.

    Talk about someone who had it all. Wow.

  10. keiths:
    But by that usage, “stopped” applies both to equilibrium in vivo and in vitro.Why do you think there’s a difference?

    Why do you think I think there’s a difference? And what do you think I think there is a difference between?

    I would say that living organisms survive by maintaining themselves in a steady state out of equilibrium from their environment. Attaining equilibrium means a dead organism.

  11. I got this question wrong:

    5.Which pathway evolved first; glycolysis or glucoenogenesis?

    The answer I think Larry is expecting:

    Glycolysis evolved first because gycolysis is the first step to making pyruvate which is needed for the full metabolic degredation of glucose. Furthermore, pyruvate is the starting point for the glucogenesis cycle.

    Larry’s answer:

    I started by pointing out there are bacteria that do not have the standard glycolytic pathway and that gluconeogenesis (synthesis of glucose) undoubtedly evolved before glycolysis.

    http://sandwalk.blogspot.co.uk/2017/02/trying-to-educate-creationist-otangelo.html#more

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