Are mutations truly random or are they guided?

There is an easy test for this. Compare two genomes, say the human and chimp genome. What you will find is that synonymous mutations (mutations which do not change the amino acid sequence) outnumber non-synonymous mutations. You can also compare the rate of change between exons and introns which again relates to protein function and stabilizing selection. Another source to test is the LTR's of ERV's. When an ERV inserts the flanking LTR's are identical. Over time these will diverge as different mutations accumulates in each LTR. What one should see is divergence over time, and that is exactly what is seen.Both the randomness of mutations and natural selection in the past can be tested for, and has been tested for.

IIRC, only about 3 mutations out of 125 to 175 mutations per person occur in a coding region. Of the rest I don't see how even a majority of them will change gene expression. I think it would be a safe bet that most mutations do not affect either gene expression or amino acid sequence in any noticeable way.

Take any two species. Compare their genomes. Homologous bases are the beginning points. Differences are the mutations. Strawman. Evolution is not change from simple to complex. It is adaptation. Bacteria have been evolving for over 3 billion years to fill their niche. That niche requires simplicity. To this day the most successful path is simplicity. Even now the vast majority of life is single celled. Why should bacteria become more complex when simplicity has served them so well for over 3 billion years? Where is your math? It has already been shown that the observed human mutation rate is consistent with the change needed to produce the differences between humans and chimps.

It works as a rough analogy. To extend the analogy, imagine if you were using an old floppy drive to copy files from one computer to the next. It just so happens that a few mistakes are made each time the file is copied leading to changes in the code. Changes that occur in the commented sections will go unnoticed while changes in the areas required for the program will either create bugs or perhaps change the program for the better.

What is actually happening with such mechanisms as the SOS response in E. coli is it increases the random mutation rate by upregulating sloppy polymerases and increases the recombination rates in areas where the DNA has been damaged. What the bacteria are doing (if you want to anthropomorphize it) is trading an increase in deleterious mutations for the chance of hitting that one mutation that will allow it to survive in harsh conditions.The problem with a specific mutations in response to specific stimuli is that competitors who randomly mutate will outsmart them. For example, let's look at the competition between bacteria and antibiotic producing fungi. Let's say that the bacteria can sense penicillin in the environment and in response produce a specific mutation that results in a B-lactamase enzyme that cleaves the penicillin. What happens when the fungus randomly mutates and produces a derivative of penicillin that is still bactericidal but is no longer recongnized by the B-lacatamase produced by the bacteria? The bacteria are gonners.I don't doubt that life COULD have a set mutational response to specific environmental cues. However, such a system would be quickly outpaced randomly mutating competitors.Edited by Taq, : No reason given.

Our side is arguing that only a few lineages have gone from simple to complex. The vast majority of lineages started simple and remain simple. On top of that, evolution does not require simple to complex, only less fit to more fit in a given environment.Bacteria have been evolving for over 3 billion years to fill niches open to simple organisms. Why would you expect a couple of months of selection to reverse this trend?

Given the low number of actual transcripts it seems to be indicative of leaky RNA transcriptase activity, IMHO. No enzyme I know of has 100% substrate specificity, and I don't see why RNA trascriptase would be any different.

If you compare the number of RNA molecules (i.e. trascripts) from a "traditionally" non-functional section of DNA with the number or RNA molecules from a functional section of DNA you will find that there are many more copies of RNA from traditionally functional DNA than non-functional DNA. The classic gene has RNA polymerase binding sites upstream of the actual coding portion allowing for transcription of the gene. By "leaky" trascriptase activity I am suggesting that RNA polymerase will bind to non-specific binding sites on occasion. When molecular biologists talk of "leaky" activity they are usually referring to non-specific activity.Just as an example, endonucleases (enzymes that cut DNA at specific DNA sequences) are famous for this type of activity. It is called "star activity". When conditions aren't perfect or the endonuclease concentration is high enough the enzyme will cut at non-specific sites.

Perhaps even overly complex as shown by the ability to delete large chunks of the mouse genome without producing a noticeable effect.There is also the possibility that evolution has favored leaky RNA polymerase activity as a way of promoting variation. As a corrolary, the study below suggests that the binding site of DNA polymerases is "looser" than it could be allowing for mutations to occur indicating an evolutionary advantage compared to complete fidelity.

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Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15803-8. Epub 2005 Oct 25.

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Probing the active site tightness of DNA polymerase in subangstrom increments.

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Kim TW, Delaney JC, Essigmann JM, Kool ET.

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Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA.

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We describe the use of a series of gradually expanded thymine nucleobase analogs in probing steric effects in DNA polymerase efficiency and fidelity. In these nonpolar compounds, the base size was increased incrementally over a 1.0-A range by use of variably sized atoms (H, F, Cl, Br, and I) to replace the oxygen molecules of thymine. Kinetics studies with DNA Pol I (Klenow fragment, exonuclease-deficient) in vitro showed that replication efficiency opposite adenine increased through the series, reaching a peak at the chlorinated compound. Efficiency then dropped markedly as a steric tightness limit was apparently reached. Importantly, fidelity also followed this trend, with the fidelity maximum at dichlorotoluene, the largest compound that fits without apparent repulsion. The fidelity at this point approached that of wild-type thymine. Surprisingly, the maximum fidelity and efficiency was found at a base pair size significantly larger than the natural size. Parallel bypass and mutagenesis experiments were then carried out in vivo with a bacterial assay for replication. The cellular results were virtually the same as those seen in solution. The results provide direct evidence for the importance of a tight steric fit on DNA replication fidelity. In addition, the results suggest that even high-fidelity replicative enzymes have more steric room than necessary, possibly to allow for an evolutionarily advantageous mutation rate.

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Not only that, but TATA boxes make up just a portion of the possible eukaryotic promoter sequences. There are also e-boxes with the sequence CACGTG. Add to that promoter regions from ERV's and their SINE and LINE derivatives, pseudogenes, promoters from recombination events involving one or both, and numts. Perhaps the best way to describe the transcriptome is "noisy".

To better understand what biologists mean by "random mutations" you would be well served by studying the two classic examples.First, the Luria-Delbruck fluctuation experiment. In this experiment they determined that mutations leading to phage resistance occurred prior to the bacteria being exposed to phage. IOW, the phage resistance (beneficial trait) occurred in an environment where it wasn't beneficial. Wiki page on the experimentThe other experiment is the Lederbergs' plate replica experiment. In this experiment they demonstrated the same thing for antibiotic resistance using a plate replica system. They were able to purify for resistant bacteria without the bacteria ever seeing antibiotics. Again, they demonstrated that the mutations leading to antibiotic resistance occurred in the absence of antibiotic.You can read the original Lederberg paper here.When biologists state that mutations are random they are saying that mutations are random with respect to fitness. A mutation does not occur at a higher rate than background simply because it is beneficial in the current environment.

Nothing?

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BMC Evol Biol. 2009 Dec 29;9:302.

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Identification and dynamics of a beneficial mutation in a long-term evolution experiment with Escherichia coli.
Stanek MT, Cooper TF, Lenski RE.

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Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824-4320, USA. mstanek@ltu.edu

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BACKGROUND: Twelve populations of E. coli were serially propagated for 20,000 generations in a glucose-supplemented minimal medium in order to study the dynamics of evolution. We sought to find and characterize one of the beneficial mutations responsible for the adaptation and other phenotypic changes, including increased cell size, in one of these populations. RESULTS: We used transposon-tagging followed by P1-transduction into the ancestor, screening for increased cell size and fitness, co-transduction analysis, and DNA sequencing. We identified a 1-bp insertion in the BoxG1 region located upstream of glmUS, an operon involved in cell-wall biosynthesis. When transduced into the ancestor, this mutation increased competitive fitness by about 5%. This mutation spread through its population of origin between 500 and 1500 generations. Mutations in this region were not found in the other 11 evolving populations, even after 20,000 generations. CONCLUSION: The 1-bp insertion in the BoxG1 region near glmUS was demonstrably beneficial in the environment in which it arose. The absence of similar mutations in the other evolved populations suggests that they substituted other mutations that rendered this particular mutation unimportant. These results show the unpredictability of adaptive evolution, whereas parallel substitutions at other loci in these same populations reveal the predictability.

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PMID: 20040094 [PubMed - indexed for MEDLINE]

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And that's just one of the mutations they studied.

Note the two experiments I discuss (Luria-Delbruck and Lederberg) above. Those are the classic experiments which demonstrated the randomness of mutations.We can also discuss differences in the genomes of species. It is observed that there are more synonymous mutations than non-synonymous mutations when comparing genomes which strongly indicates random mutations filtered through selection.As to directed v. random, you still need to address why humans are born with genetic diseases due to mutations. At least to me, this seems like a contradiction to the directed mutation argument. Also, in the two experiments above they actually calcuate the rate at which the beneficial mutations occur. They occur only once in every hundred million replications or so. Does that sound like a directed process to you, where the beneficial mutation only arises once in every 100 million divisions? Sure doesn't to me. It's a two way street. I have presented the scientific evidence, but instead of focusing on that you have chosen to talk about how people have persecuted you. If you don't want to discuss your religious beliefs then don't. Discuss the science. Actually, I would strongly suspect that glucose is slowly oxidized in the presence of oxygen, just at a much slower rate than is seen in the cell. Also, anyone who has done any cooking has probably experienced the black aftermath of scorching sugar.Also, pointing to complexity gets us nowhere. "Wow, that's complex" is an ok observation, but it is not an explanation. The problem is that you seem to be pushing this observation as an explanation. We have seen this too many times to count.

You need to understand how biologists are approaching the problem. Biologists need an explanation for DIRECTIONAL change. They need an explanation as to why there are more changes in one area of genome than in another. They need to a way of determining which genes are involved in disease, and which are involved in divergent characteristics. The explanation for all of this is selection. No one is saying that the creation of variation is not important. Rather, selection explains the important observations. Several peer reviewed scientific articles have been cited by myself and others. Perhaps you should comment on those. No one is claiming that evolution is guided by random mutations. You are confusing phenotype plasticity with evolution. They are not the same thing. Evolution does not occur to one individual during it's lifetime. Evolution occurs at the level of the population over generations.Also, where are people with gills? Surely populations living along beaches need to be able to swim better, so where are there gills? Can you explain this?Next, can you tell us how achondroplastia (dwarfism) and hemophilia are adaptations? People are born with mutations causing these conditions, and that mutation is not found in either parent. So what niche are these people being guided to? Resistance comes about through random mutation, as I have already shown in the post above (see the plate replica experiment). These mutations occur in the ABSENCE of antibiotics, so this can not be a defense mechanism since there is nothing to defend against when these mutations occur. These bacteria did not exist before the experiment started, and they came about through mutation of their DNA. The scientific literature is loaded with examples of resistance coming about through mutation of DNA. This is exactly the type of evolution that you have asked for, and now you dismiss it.As for the argument "they are still bacteria", it's nothing more than a ploy on your part to lessen the impact of evidence that shoots holes in your argument. The common ancestor of humans and chimps was an ape, and humans and chimps are still apes, so I would guess that you have no problem with humans and chimps sharing a common ancestor, right? Humans and bears are both mammals, as was their common ancestor. Just mammals turning into mammals. No problem, right? Humans and fish are both vertebrates, as was their common ancestor. Just vertebrates turning into vertebrates. You have no problem with this, right? Humans and amoebas are both euakaryotes, as was their common ancestor. Just eukaryotes turning into eukaryotes. Surely you have no problem with this, right?Are you starting to get a sense of why the "they are still bacteria" canard is foolish? What you are playing is the famous "creationist name game". You somehow think that if you can call the parent and daughter species by the same name that evolution didn't occur. What you seem to ignore is that in experiments like the one above new bacteria emerge, bacteria that did not exist at the start of the experiment. This is evolution. It is descent with modification. We are saying that these things came about through random mutation AND selection. You should at least describe our argument correctly before criticizing. This is false. There are experiments that you can run to test whether or not random mutation and selection were responsible for the differences seen between species. One way is to compare the genomes of the two species and to find the ratio of synonymous to non-synonymous mutations (i.e. the ratio of mutations which do not change the amino acid sequence of proteins compared to those that do). What you should find, if random mutations and selection are true, is that the synonymous mutations outnumber the non-synonymous mutations. This is exactly what we see. Instead of whining why don't you focus on the science that has been presented. Why not? Compare the genomes of a simple and complex organism. The differences in DNA are the reason for the difference. Random mutations coupled with selection changes DNA in a way that increases fitness. We know that these mutations are random because of observations such as those in the Luria-Delbruck fluctuation experiment and the Lederbergs' plate replica experiment as I discussed above (and you ignored).

Just to expand on this . . .Cairn wasn't crazy for initially sticking his head out. In the classic lactose experiments these mutants did appear at rates that were inconsistent with known mutation rates. Guided mutations were certainly a possibility, and Cairn could have garnered quite the attention if he turned out to be right. However, further research indicated that the presence of lactose did not induce these mutations. Rather, DNA damage due to starvation induced these mutations through the upregulation of polymerases with lower fidelity (i.e. enzymes that produced more mistakes during replication) and enzymes that increased the rate of recombination. There is one trick that I use often. If you do a search on http://www.pubmed.com look for a small box on the right hand side towards the top. It will have a hyperlink for listing all of the free articles available for that search (e.g. "Free Full Text (17)"). I have found that this is really handy for doing initial research on a topic.