[Babcock_Hall]

A colleague posed this question to me, and so I thought I would post it.  It is odd, for example, that we have both leucine and isoleucine among the twenty common amino acids.  Are there any good review articles or books that anyone knows about which discuss this question?

[discodermolide]

Well I googled "the amino acids book" and got several hits which may be of interest to you.
Perhaps we could e-mail the space dino. author of last year?

[curiouscat]

It is odd, for example, that we have both leucine and isoleucine among the twenty common amino acids. 

You mean they are so similar, doesn't make sense to have both?

[Babcock_Hall]

Curiouscat, Exactly.  Peter Schultz (whose research on incorporating nonnatural amino acids into proteins obviously bears on this question) sometimes used to ask rhetorically in his seminars, "If you were God and you had made leucine one of the nineteen amino acids, would you waste the twentieth on isoleucine?"  Someone is said to have asked back, "OK, Peter, if you were God, what would the twentieth amino acid have been?"  Peter stammered for a minute and said, "Well, I don't know, but I do know one thing.  I would not have rested on the seventh day."

discodermolide,  I did not follow your comment.

[discodermolide]

Breslow's paper on the origins of life, which mentioned dinosaurs and was retracted for self-plagerism.
He is an expert on such matters.

[discodermolide]

The reference is Evidence for the Likely Origin of Homochirality in Amino Acids, Sugars, and Nucleosides on Prebiotic Earth: Ronald Breslow*
Department of Chemistry, Columbia University, New York, New York 10024, United States
JACS, 2012, doi.org/10.1021/ja3012897

[Babcock_Hall]

Here is a link to the discussion of the alleged self-plagiarism:
http://blogs.nature.com/news/2012/04/eminent-chemist-denies-self-plagiarism-in-space-dinosaurs-paper.html

However, this is a different question from the one that I asked, which is why did we get the twenty amino acids that we did.  For example, why are there no amino acids with ether linkages, but there is one with a thioether.  Why not more that are like histidine, which can be a nucleophile, an acid, a base, or a ligand to a metal ion?

Edit: link corrected.

[Arkcon]

Well, discussions of this sort can get circular rapidly.  IMHO, when scientists start to ask Why? so much duplication and try to figure out what the process of natural selection is "thinking" they're making the same arguments that YENC theists make when they say "God did it."  I'll admit, however, that is is a little bit fun:

For example, why are there no amino acids with ether linkages, but there is one with a thioether.

I don't know of any other ether linkages in eukaryote and prokaryote biomolecules.  I do know that ether linkages are found in the lipids of some archeobacteria.  So maybe its just a pathway that was lost, or not exploited extensively.  This is a fundamental fact:  some pathways are taken, and exploited, and all other life forms follow along, or else that can't exploit that biomolecule as a nutrient source.  Seriously, don't eat those particular archeobacteria -- you can't metabolize those lipids and you will sharse red oil that night. http://science.slashdot.org/story/09/11/22/2313225/is-that-sushi-hazardous-to-your-health  Perhaps its just luck why one was taken.

Why not more that are like histidine, which can be a nucleophile, an acid, a base, or a ligand to a metal ion?

We've got one.  Why would we need another?  I know, duplication and degeneracy are often happening, but not always.  Why sometimes, and not always or never?  I can't answer that either.

[ramboacid]

It is odd, for example, that we have both leucine and isoleucine among the twenty common amino acids. 

You mean they are so similar, doesn't make sense to have both?

I don't know much about this topic, but if leucine and isoleucine are so similar can they be substituted interchangeably in peptides without deleterious effects? If there's a documented case in which you can have only one and not the other then that one case would be useful for some justification.

[Babcock_Hall]

Well, discussions of this sort can get circular rapidly.  IMHO, when scientists start to ask Why? so much duplication and try to figure out what the process of natural selection is "thinking" they're making the same arguments that YENC theists make when they say "God did it."  I'll admit, however, that is is a little bit fun:
SNIP
We've got one [histidine].  Why would we need another?  I know, duplication and degeneracy are often happening, but not always.  Why sometimes, and not always or never?  I can't answer that either.

Why not have a histidine-like amino acid but with a pyrazine or pyridine ring?  At least there are pyridine derivatives in nature.  Or better still, why didn't nature include hydroxyproline as the 21st amino acid, as opposed to having to make it via a posttranslational modification?

[Arkcon]

What are hydroxyproline and hydroxylysine used for?  Where are they found, and how can you relate those particular residues to the early development of biomolecules?  And can you extrapolate that explanation to other questions you might have?

[curiouscat]

One of the assumptions here is that nature is indeed perfectly optimized? Not a work in progress?

[Babcock_Hall]

What are hydroxyproline and hydroxylysine used for?  Where are they found, and how can you relate those particular residues to the early development of biomolecules?  And can you extrapolate that explanation to other questions you might have?

A fair point, but I have to wonder whether one can say that about every noncanonical amino acid.  And why stop at 20 amino acids when you have 61 codons to play with (plus three for stops)?  Look at how many coenzymes there are and how universally they are distributed.  That is a good indication that the amino acid side chains cannot do all of the chemistry that enzymes have to be able to do.

[Yggdrasil]

There's no real definitive answer to this question but here are some of my thoughts on the issue.  Many people when they propose adding new amino acids look at polar amino acids (such as the ethers, hyroxyproline or hydroxylysine proposed in this thread).  These polar amino acids seem much more interesting than the simple aliphatic amino acids because they can do so much more stuff (like hydrogen bond, bind metals, aid in catalysis, etc).  However, the "boring" aliphatic residues are essential for a process much more important than catalysis, namely protein folding.  In addition to being a prerequisite for any functional role the protein plays (including catalysis), proper protein folding is also important because misfolded proteins are toxic to the cell.  Thus, evolution has very strongly selected for factors that promote protein folding.

Protein folding is largely driven by the hydrophobic effect, and the protein will fold to conceal its nonpolar residues within the interior of the protein and expose its polar residues on the exterior.  Therefore, the packing of non-polar residues within the interior of the protein is highly important to its stability.  In addition, evolution tunes the stability of proteins so that instead of being completely rigid, they undergo important conformational changes that contribute to their functions, like catalysis or binding.

A similar principle also applies to many protein-protein interactions where the association of two complementary hydrophobic surfaces provides most of energy to stabilize the binding interaction.  In most cases, the hydrophobic effects drives the stability of such interactions while hydrogen bonding and salt bridge formation provide the specificity for such interactions.  (Getting away from the protein world, the association of two strands of DNA into a double helix illustrates this point well.  The hydrogen bonding between the bases do not contribute much to the thermodynamic stability of the double helix; there is very little energetic difference between the hydrogen bonding of the bases to water in ssDNA and the hydrogen bonding between complementary bases in dsDNA.  Rather, the stacking between the aromatic rings of the bases, sequestering these fairly hydrophobic parts within the interior of the double helix, that provides the energy to drive the formation of dsDNA.  The base pairing merely insures specificity for the interactions.)   

Therefore, nature requires a number of nonpolar amino acids of varying shapes and sizes in order to be able to create well-packed protein interiors and protein-protein interaction interfaces.  The variety of hydrophobic amino acids is also important for tuning the strength of these folding and binding interactions.  Of course, making a variety of hydrophobic amino acids is difficult because synthesizing aliphatic chains of different lengths requires carbon-carbon bond formation.  Thus, perhaps having the closely related set of isoleucine, leucine, and valine (in addition to the aromatics and other nonpolar residues) represent some sort of compromise between systems that lack variety in the shapes of the hydrophobic residues versus systems that require very complex biosynthetic schemes.

[Arkcon]

Look at how many coenzymes there are and how universally they are distributed.  That is a good indication that the amino acid side chains cannot do all of the chemistry that enzymes have to be able to do.

Exactly.  And many of those needs are not preserved across all forms of life, which are theoretically developed from the same primordial biological process.  The production of collagen by animal tissues isn't done by other living things.  Some living things can use a variety of biocompounds to detect light, and some don't, but an even smaller subset need to focus and process a visual image.