User:Grabriggs/sandbox

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The Pillars

1. Wikipedia is a user driven online encyclopedia.

2. Wikipedia strives to represent a neutral point of view. Wikipedia does not take sides in a disagreement.

3. Wikipedia is improved by volunteers and people that want to create valuable free information.

4. When working in Wikipedia users should respect one another and maintain professional relationships.

5. Since Wikipedia is always evolving there are no set rules beyond the pillars.

Summary of characteristics of target article

A good article is a thoughtful and well written article in wikipedia that is comparable to a traditional encyclopedia article. It should be neutral and contain verifiable information with in line footnotes to reputable references. A good article should be informative and provide a good overview of a topic with details pertaining to important aspects of the topic. There should be no obvious flaws and the article should contain ample pictures, charts, graphs, etc.

Practice Nipah Article

Nipah virus is a potentially fatal virus, killing approximately 70% of humans infected. This virus was originally identified in Malaysia and is also found naturally occurring in Bangladesh and more rarely in India. Its ability to pass from person to person in a limited fashion and ability to evolve quickly due to its RNA makeup have caused some concern in the medical community that it could become more easily spread and start a pandemic. This virus was used as a starting point for the pandemic virus created for the movie Contagion. Research is currently being conducted as to how Nipah virus spreads between humans. There is some evidence that a respiratory pathway is possible.

Information on Neutral Mutation

Articles Referenced in Preliminary Research

Akashi, H; Osada, N; Ohta, T (2012 Sep). "Weak selection and protein evolution.". Genetics 192 (1): 15–31. PMID 22964835. Retrieved 7 October 2013.

“For proteins, new mutations fall into two main fitness classes: strongly deleterious mutations that natural selection quickly eliminates from populations and neutral mutations that drift to fixation with probabilities equal to their initial frequency. Neutral mutations have smaller fixation probabilities in larger populations than in smaller populations, but this difference is exactly matched by the higher mutational input in larger populations, and the expected rate of neutral divergence is simply the mutation rate (and is independent of population size)”

Paper goes on to discuss the role of neutral mutation and molecular clocks. It gives a general history of neutral theory, its change to nearly neutral theory, and the evidence for and against these models.

It gets a little into the math, which I sort of want to avoid other than maybe laying down a few of the basic equations. One important point states “recent analyses often employ the ratio of nonsynonymous to synonymous DNA divergence per site (dN/dS) to estimate fn (fraction of neutral mutations).”

Waxman, D. (16 March 2012). "Population Growth Enhances the Mean Fixation Time of Neutral Mutations and the Persistence of Neutral Variation". Genetics 191 (2): 561–577. doi:10.1534/genetics.112.139220. Retrieved 7 October 2013.

Schrider, D. R.; Houle, D.; Lynch, M.; Hahn, M. W. (3 June 2013). "Rates and Genomic Consequences of Spontaneous Mutational Events in Drosophila melanogaster". Genetics 194 (4): 937–954. doi:10.1534/genetics.113.151670. Retrieved 7 October 2013.

Additional Articles

Duret, L. (2008) Neutral theory: The null hypothesis of molecular evolution. Nature Education 1(1)

This article is short but gives an overview of the neutral theory of evolution. I think we are going to need to refer to the overarching view that neutral mutation is involved in this theory. At first I was concerned that the theory itself was not part of our topic and addressed elsewhere. However, our topic seems to be an important piece of this theory and some coordination may be necessary in my opinion. Mutation without selective pressure seems to play a prominent role in neutral theory and serves as a null hypothesis when testing biased or selective mutation. Grabriggs (talk) 01:07, 20 October 2013 (UTC)

Nei M (2013) Mutation-Driven Evolution (Oxford Univ Press, Oxford, UK)

This is a recent book with a lot of information. However, the JHU library doesn't own it so I was only able to browse it for 5 minutes. I placed a request for a loan but not sure how that works, and I could only request for 7 days.

Nei, M., Suzuki, Y., & Nozawa, M. (2010). The neutral theory of molecular evolution in the genomic era. Annual Review of Genomics & Human Genetics, 11(1), 265.

This gives a pretty good historical perspective. It looks at the initial protein sequencing experiments that showed sequence divergence but that the proteins still had the same function. It elaborates on the difference between what molecular biologists and population geneticists consider neutral mutations i.e one looking at sequence data and the other looking at the statistics of measuring fitness in populations to determine neutrality. There is a good discussion on the role of neutral mutation and molecular clocks. It describes most of the statistical tests used in measuring fitness, selection, etc.

Sawyer, S. A., Parsch, J., Zhang, Z., & Hartl, D. L. (2007). Prevalence of positive selection among nearly neutral amino acid replacements in drosophila. Proceedings of the National Academy of Sciences of the United States of America, 104(16), 6504.

This is a study based on nonsynonymous mutation frequencies (which should have selection pressure so can measure for neutrality) versus synonymous mutation frequencies (which should always be neutral, though not sure how codon bias works for this). The introduction is useful in explaining the context for this type of comparison. Their data on Drosophila melanogaster basically says that 95% of the nonsynonomous mutations show positive selection, however, the selection coefficient is very small and their fixation should be due mostly to drift as opposed to hard selection. However, they only classify mutations with very small selection coefficients as nearly neutral and not truly neutral, so not sure if the data will help us. In looking at the figures in this article, it makes me wonder about finding some graphs that represent a lot of data for our images.

Boyko, A. R., Williamson, S. H., Indap, A. R., Degenhardt, J. D., Hernandez, R. D., Lohmueller, K. E., et al. (2008). Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genetics, 4(5), 1.

This article looks at a over 40,000 SNPs in over 10,000 genes and predicts 27–29% of amino acid changing (nonsynonymous) mutations are neutral or nearly neutral, 30–42% are moderately deleterious, and nearly all the remainder are highly deleterious or lethal. They infer that 10–20% of amino acid differences between humans and chimpanzees were fixed by positive selection, with the remainder of differences being neutral or nearly neutral. Probably just a good article to cite for more data to back up the prevalence of neutral mutations.

Walser, J. C., Ponger, L., & Furano, A. V. (2008). CpG dinucleotides and the mutation rate of non-CpG DNA. Genome Research, 18(9), 1403.

Very briefly, this discusses Line 1 retrotransposon mutations (which are assumed to be all neutral it seems) in humans and chimpanzees. It provides evidence on how CpG mutations increase non-CpG mutations. This effect makes it difficult if not impossible to monitor uniform genome-wide neutral mutation rate.

Venetianer, P. á. (2012). Are synonymous codons indeed synonymous? Biomolecular Concepts, 3(1), 21.

This is a review showing mechanisms how synonymous codons can effect protein expression. I would think it would be mostly useful for the references cited in showing how difficult it is to gauge what is truly a neutral mutation.

Yi, S. (2013) Neutrality and Molecular Clocks. Nature Education Knowledge 4(2):3

This is a nice introduction and summary to the role of neutral mutation in molecular clocks.

Tomizawa J. (2000) Derivation of the relationship between neutral mutation and fixation solely from the definition of selective neutrality. PNAS June 20, 2000 vol. 97 no. 13 7372-7375.

This article looks at neutral mutation and fixation. It also has a definition to cite on what neutral mutation is. I've been looking for something to cite that actually describes our topic.

Duret, L. (2002) Evolution of synonymous codon usage in metazoans. Current Opinion in Genetics & Development. Volume 12, Issue 6, 1 December 2002, Pages 640–649

This article discusses how synonymous mutations may actually be driven somewhat by natural selection due to a variety of factors.

Neutral Mutation Outline

Introduction

It looks like all that is done so far is the intro. I think we can tweak it and it will work for us. I also made a comment on the article's talk page about the table titled mutation. I'm not sure if it helps the article or if we want to find a place for it.

History

The Nei article looks like a good reference for this section. It looks like a good historical overview. We can begin with Darwin's realization of the occurrence and consequences of traits not affecting fitness of individuals. "Variations neither useful nor injurious would not be affected by natural selection, and would be left either a fluctuating element, as perhaps we see in certain polymorphic species, or would ultimately become fixed, owing to the nature of the organism and the nature of the conditions."

Darwin, C. (1987; 1859). On the origin of species by means of natural selection : Or the preservation of favoured races in the struggle for life (Special ed.). Birmingham, Ala.: Gryphon Editions.

Synonomous Mutations

We've got a few articles to reference here.

I think we could find a DNA codon table and insert it here to show the different possibilities for synonymous mutations. Grabriggs (talk) 05:47, 26 October 2013 (UTC)

Aminoacids table

Measurements of Neutrality

This section has some good references as well. The meat of our article may exist in this section and the section on synonomous mutations.

Molecular clocks

This is covered in another Wikipedia article, but I think the role of neutral mutation in the calibration of molecular clocks should warrant a section in our article.

Impact on Evolutionary Theory

I'm thinking the Duret article explains the neutral theory and the utility of the null hypothesis with neutral mutation for a closing section.

Amino-acid biochemical properties

Nonpolar

Polar

Basic

Acidic

Termination: stop codon

Standard genetic code (NCBI table 1)

1st base	2nd base								3rd base
	T		C		A		G
T	TTT	(Phe/F) Phenylalanine	TCT	(Ser/S) Serine	TAT	(Tyr/Y) Tyrosine	TGT	(Cys/C) Cysteine	T
	TTC		TCC		TAC		TGC		C
	TTA	(Leu/L) Leucine	TCA		TAA	Stop (Ochre)[B]	TGA	Stop (Opal)[B]	A
	TTG[A]		TCG		TAG	Stop (Amber)[B]	TGG	(Trp/W) Tryptophan	G
C	CTT		CCT	(Pro/P) Proline	CAT	(His/H) Histidine	CGT	(Arg/R) Arginine	T
	CTC		CCC		CAC		CGC		C
	CTA		CCA		CAA	(Gln/Q) Glutamine	CGA		A
	CTG		CCG		CAG		CGG		G
A	ATT	(Ile/I) Isoleucine	ACT	(Thr/T) Threonine	AAT	(Asn/N) Asparagine	AGT	(Ser/S) Serine	T
	ATC		ACC		AAC		AGC		C
	ATA		ACA		AAA	(Lys/K) Lysine	AGA	(Arg/R) Arginine	A
	ATG[A]	(Met/M) Methionine	ACG		AAG		AGG		G
G	GTT	(Val/V) Valine	GCT	(Ala/A) Alanine	GAT	(Asp/D) Aspartic acid	GGT	(Gly/G) Glycine	T
	GTC		GCC		GAC		GGC		C
	GTA		GCA		GAA	(Glu/E) Glutamic acid	GGA		A
	GTG[A]		GCG		GAG		GGG		G

^A Possible start codons in NCBI table 1. ATG is most common. The two other start codons listed by table 1 (GTG and TTG) are rare in eukaryotes. Prokaryotes have less strigent start codon requirements; they are described by NCBI table 11.

^{B ^ ^ ^} The historical basis for designating the stop codons as amber, ochre and opal is described in an autobiography by Sydney Brenner and in a historical article by Bob Edgar.