User:Aarankin/sandbox

Article Evaluation
Evaluating the wikipedia article Neo-Darwinism.

The article is coherent, there is very little that distracts from the main topic. The article does not seem biased towards any particular position. It just explains the origins and history of Neo-Darwinism. I do not notice any viewpoints that are not appropriately represented. All the links I clicked worked, and the sources I checked did support the facts they were used to cite. Almost all the facts in the article have a citation supporting them. The sources cited all seem fair and unbiased. One source talks about various viewpoints that are "Anti-Darwinist" but includes a note that these viewpoints are only viewpoints and do not necessarily conflict with one another. The section relating the term to Modern Synthesis seems a bit sparse even with the graphic to flesh it out and could probably use some additional content. The talk section for this article is very long, and it seems to have had quite a lot of controversial edits over the years, including many creationist biases that have had to be removed. The article was nominated for deletion in 2007, as many users had argued that it should be merged with the article for Modern Synthesis. No conclusion was reached and the article has not been deleted. The article on Neo-Darwinism differs from the kinds of discussions we have in class as the article is mostly focused on the history of the term rather than the theoretical implications.

Article work
I selected the article Nonsynonymous substitution. This article is a stub and contains very little content. I plan to expand the article by elaborating on the definition of the term, the kinds of mutations that result from nonsynonymous substitutions, the phenotypic effects of these mutations, and research examples of such mutations. I also plan to elaborate on the connection between Nonsynonymous substitution and Ka/Ks ratio as the current explanation is vague.

Two external links included in the original stub are broken and the sites cannot be reached.

Article First Draft
Original word count: 85 words

Final word count for first draft: 248

Strategy to complete article:

-Expand current sections to include more citations and go more in depth on the topic.

-Add a section providing at least 2 examples of mutations that are nonsynonymous substitutions (Examples of research involving the topic)

-Find 6 more references

-Add a section addressing the Ka/Ks ratio connection

-Discuss in depth the connection to Kimura's Neutral Theory

Peer reviews
reviewed Alex Jaffery and mistakenly reviewed Aeboornizian instead of Alex Rakestraw on November 17th.

Did not receive any peer reviews.

= Nonsynonymous substitution = From Wikipedia, the free encyclopedia

A nonsynonymous substitution is a nucleotide mutation that alters the amino acid sequence of a protein. Nonsynonymous substitutions differ from synonymous substitution s, which do not alter amino acid sequences and are silent mutation s. As nonsynonymous substitutions result in a biological change in the organism, they are subject to natural selection.

Nonsynonymous substitutions at a certain loci can be compared to the the synonymous substitutions at that loci to obtain the Ka/Ks ratio. This ratio is used to measure the evolutionary rate of gene sequences. If a gene has lower levels of nonsynonymous than synonymous nucleotide substitution, then it can be inferred to be functional because a Ka/Ks ratio < 1 is a hallmark of sequences that are being constrained to code for proteins.

Nonsynonymous substitutions are also referred to as replacement mutations

Types of nonsynonymous substitions
There are several common types of nonsynonymous substitutions.

Missense mutation s are nonsynonymous substitutions that arise from point mutations, mutations in a single nucleotide that result in the substitution of a different amino acid, resulting in a change to the protein encoded.

Nonsense mutation s are nonsynonymous substitutions that arise when a mutation in the DNA sequence causes a protein to terminate prematurely by changing the original amino acid to a stop codon. Another type of mutation that deals with stop codons is known as a readthrough mutation, which occurs when a stop codon is exchanged for an amino acid codon, causing the protein to be longer than specified.

Natural Selection on nonsynonymous substitutions and the "Nearly Neutral" Theory
Studies have shown that diversity among nonsynonymous substitutions is significantly lower than among synonymous substitutions. This is due to the fact that nonsynonymous substitutions are subject to much higher selective pressures than synonymous mutations. Motoo Kimura (1968) determined that calculated mutation rates were impossibly high, unless most of the mutations that occurred were either neutral or "nearly neutral". He determined that if this were true, genetic drift would be a more powerful factor in molecular evolution than natural selection. The "nearly neutral" theory proposes that molecular evolution acting on nonsynonymous substitutions is driven by mutation, genetic drift, and very weak natural selection, and that it is extremely sensitive to population size. In order to determine whether natural selection is taking place at a certain loci, the McDonald–Kreitman test can be performed. The test consists of comparing ratios of synonymous and nonsynonymous genes between closely related species to the ratio of synonymous to nonsynonymous polymorphisms within species. If the ratios are the same, then Neutral theory of molecular evolution is true for that loci, and evolution is proceeding primarily through genetic drift. If there are more nonsynonymous substitutions between species than within a species, positive natural selection is occurring on beneficial alleles and natural selection is taking place. Nonsynonymous substitutions have been found to be more common in loci involving pathogen resistance, reproductive loci involving sperm competition or egg-sperm interactions, and genes that have replicated and gained new functions, indicating that positive selection is taking place.

Research involving nonsynonymous substitutions
Research on accurately modeling rates of mutation has been conducted for many years. A recent paper by Ziheng Yang and Rasmus Nielsen compared various methods and developed a new modeling method. They found that the new method was preferable for its smaller biases, which make it useful for large scale screening, but that the maximum-likelihood model was preferable in most scenarios because of its simplicity, and its flexibility in comparing multiple sequences while taking into account phylogeny.

Further research by Yang and Nielsen found that nonsynonymous to synonymous substitution ratios varied across loci in differing evolutionary lineages. During their study of nuclear loci of primates, even-toed ungulates, and rodents, they found that the ratio varied significantly at 22 of the 48 loci studied. This result provides strong evidence against a strictly neutral theory of molecular evolution, which states that mutations are mostly neutral or deleterious, and provides support for theories that include advantageous mutations.