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What contribute to the variation of protein sequence across different species (e.g. phenotype, environment, evolutionary pressure) and how do those factors contribute to the variation?

I have tried to search using google + google scholar but they generally show papers discussing why and how the protein conserved across species rather than why/how the protein diverged across species. Please help me on this and references/sources are very important and highly appreciated. Thank you!

An example to clarify my question. The gene CD81 is not identical among human, chimp, rat, chicken based on this identity matrix from ClustalW2. Why is CD81 not identical in all species? What factors cause the different in CD81s? How do those factors cause that (e.g. evolutionary pressure)? # #

Percent Identity Matrix - created by Clustal2.1

# #

 1: sp|P60033|CD81_HUMAN    100.00  100.00   93.22   82.55
 2: sp|P60034|CD81_PANTR    100.00  100.00   93.22   82.55
 3: sp|Q62745|CD81_RAT       93.22   93.22  100.00   82.55
 4: tr|F1NW06|F1NW06_CHICK   82.55   82.55   82.55  100.00
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closed as too broad by WYSIWYG Dec 16 '16 at 19:22

Please edit the question to limit it to a specific problem with enough detail to identify an adequate answer. Avoid asking multiple distinct questions at once. See the How to Ask page for help clarifying this question. If this question can be reworded to fit the rules in the help center, please edit the question.

  • $\begingroup$ Welcome to Biology.SE. What contribute to the variation [..]. The maintenance of genetic (and therefore protein and phenotypic) variation is one of the main question of evolutionary biology. It is extremely studied and there are a lot of processes that either retain or remove genetic variation. The question is too broad. [..] and how do they influence? How do they influence what? (I am not sure what they stands for either) It is unclear. $\endgroup$ – Remi.b Oct 22 '15 at 1:48
  • $\begingroup$ Thanks Remi.b for your feedback! I have clarified my word and add an example. $\endgroup$ – stareagle130 Oct 22 '15 at 3:18
  • $\begingroup$ I didn't like my answer so I deleted it. It is hard to answer such a broad question. However, there is one result you probably want to remember. If you can assume that both species and all of their ancestral lineages up to their Most Recent Common Ancestor, had the same mutation rate $\mu$, then, the substitution rate is $\mu$ as well. $\endgroup$ – Remi.b Oct 22 '15 at 13:42
  • $\begingroup$ It is indeed general so that's why I have such a hard time answering as well as finding literature. Anyway, I have found my answer related to the keyword "Neutral evolution" or "Molecular evolution". $\endgroup$ – stareagle130 Oct 23 '15 at 1:40
  • $\begingroup$ I've edited the English in your title. Hope you don't mind. $\endgroup$ – David Jun 19 '16 at 12:30
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I have found an acceptable answer for my question. Just post here if any interest in it. Pardon my English.

Source:

Nei et. al. 2010. The Neutral Theory of Molecular Evolution in the Genomic Era. Annu. Rev. Genom. Human Genet.

Evolution and point mutation cause the sequence difference of the same functional protein across species. Neutral theory of molecular evolution shows that speciation level of evolution is an accumulation of molecular level of neutral evolution. In neutral evolution, the mutation only occur at a scope of point mutation in sequence in the manner that the function of the protein is retained. Overtime, speciation occurs yet the function carried out by that specific protein is still necessary and is conserved across species. Difference in protein sequence of the same functional protein is the residuals of random point mutation.

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I would dispute your conclusion that it is simply neutral evolution. Neutral change absolutely does occur but it is not a complete answer to your question. Similar proteins in different organisms are not in the same environment and rarely do exactly the same thing.

For example, your three mammals will have similar but not identical body temperatures while the chicken's body temperature will be slightly higher at 42 degrees. Enzyme efficiency is highly temperature dependent so it is likely that some of the difference is attributable to optimal function at different temperatures. I don't know anything about CD81 specifically but it is often the case that gene regulation pathways are similar, but not identical, between organisms so that you may find that it needs to interact with slightly different proteins in a slightly different way.

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