Introduction to Genetics

Which of course implies evolution again. Fewer differences between what and what? I think the evo baggage of that abstract has thrown me. And what "function" is there in "non-coding" regions which I guess refers to pseudogenes or junk DNA that apparently retains some function or what?

I think part of the trouble is that Taq jumped to the punchline without filling in all the details. The problem is the subject is very complex and is difficult to sum-up in a single post. He is trying to get across how we recognize differences in genomes between two separate species. But, I think we should back up and discuss the details in more ... uuhhh ... detail.

A typical Eukaryotic gene consists of a promoter region, a non-coding spacer (~ 30bp), a start codon, introns, exons, a stop codon another non-coding section and a transcription terminator. There is also an initiator sequence upstream of the promotor somewhere between a couple hundred bp to a couple thousand bp. You will see this in the video below swing in and touch the promoter complex to initiate transcription.

The promoter region first must be activated before transcription can occur. Once activated, the double stranded DNA (dsDNA) can be unzipped and the polymerase can bind to the START CODON. Transcription is then initiated and the DNA strand is transcribed into messenger (mRNA). The mRNA is then processed post-transcriptionally, where the INTRONS are snipped out by enzymes and the EXONS spliced back together to from the mature mRNA. Mature mRNA is then translated into a protein that goes from the START CODON to the STOP CODON.

Transcription Video

Translation Video

The protein is made up of various DOMAINS that serve various functions from anchoring to the membrane, engaging target molecules and allowing specific folding patterns.

The next step is to fold the protein into its function 3D shape. This can occur spontaneously or can be assisted by the endoplasmic reticulum (ER) or other enzymes. This folding is critical to the function of the protein. What it does is expose the functional amino acid residues so they can do their job.

Protein folding assumes the form of secondary, tertiary and quatenary structures.

You may be aware of most or all of this, but understanding this is foundational to understanding the significance of mutations and what mutations do to the organism.

I will post more about mutations in a little while.

HBD

Ok, so we will deal with one specific type of mutation in this post; what we call point mutations.
Point mutations are changes in a single nucleotide. They fall into tree categories: substitutions are changes from one base pair to another base pair. Insertions and deletions should be self explanatory and are what Taq referred to as indels.

So what are the effects of point mutations?

Let's review the structure of a gene again:

a promoter region, a non-coding spacer, a start codon, introns, exons, a stop codon another non-coding section and a transcription terminator.

Introns are clipped out of the pre-mRNA and are typically disassembled and recycled (there are occasions where they contain regulatory sequences, but they are usually non-coding). Introns can represent a significant portion of the pre-mRNA - 60% of the pre-mRNA can be introns. There are also non-coding sections between the promoter and the start codon and also at the terminal end of the mRNA. Any point mutation within these regions will be effectively neutral, since they are not translated into proteins. As you might imagine, this is where the vast majority of mutations will be preserved.

So what happens if a point mutations occurs in a coding region?

As you may know, a protein is encoded by a sequence of 3 bases (*) that are called codons.

Note: this chart is the coding for the mRNA - DNA bases would be complimentary.

The START CODON is Methionine (Met) which has the aa sequence of AUG. A mutation in this codon will inactivate the gene and prevent transcription.

An insertion or deletion within a coding region is typically fatal to the gene since it will cause a frameshift which would drastically alter the protein sequence.

A substitution, however, can have various effects on a gene.

Let's say you have a codon with the sequence CUU which codes for Leucine (Leu) and there is a substitution in the third position that substitutes an A for the U. Now look on the chart and you will see that CUA also codes for Leu. So the effect of the substitution is neutral - absolutely no effect on the gene. This is referred to as a silent mutation or synonymous substitution.

Now what if you had a mutation in that CUU codon in the first position that substituted a G for the C. Now the codon is GUU and it codes for Valine (Val). So now you have a protein with a different aa sequence. This is referred to as a missense mutation. There are basically three types of missense mutations, conservative, semi-conservative and radical. A conservative substitution replaces an amino acid with an amino acid with very similar properties. The effect can be very small to virtually neutral. A semi-conservative substitution replaces an amino acid with one that has different properties such as from a basic amino acid to an acidic amino acid. The result can be mild to severe depending on the domain in which the substitution occurs. A radical substitution replaces an amino acid with one that is radically different. This often results in problems, however, it can provide the protein with a novel function.

As you can see by the codon chart above, there are lots of substitutions that could occur that would have neutral effects on the protein as they would be synonymous substitutions.

A third type of substitution is a non-sense mutation. In this case the change in aa sequence results in a stop codon. For example, UAU codes for Tyrosine (Tyr). If there is a mutation in the third codon where an A is substituted for the U, the result is a stop codon. This substitution will result in a truncated protein, which would normally result in a non-functional protein. However, if there is another copy of the gene somewhere in the genome, the newly truncated protein may actually serve a functional purpose (but that is another story).

A note as to the source of these mutations. Most mutations in DNA occur during replication. While replication is very accurate, it is not perfect. Occasionally, the wrong base is inserted and repair mechanisms just don't catch it and the change is simply conserved in the organism. Another source is DNA damage. DNA can be damaged by various sources, such as UV radiation, and when a break occurs, repair mechanisms try and put it back together. However, the damage can be bad enough that the repair mechanisms can't figure out what the original strand was like, so it does the best it can. This can lead to cancerous growth.

Another point; since we are talking about heritable mutations, these mutations must occur in sex-cells. Mutations in somatic cells are not transmitted to the offspring. If you understand the process of meiosis, you would know that that process is ripe for these types of mutations. If you would like more information on meiosis and mitosis, I can do something on that as well.

As a final point, these processes described above are not speculation but are well studied in the laboratory using model organisms such as the fruit fly, C. elegans and Arabidopsis. How we can go from this information to evidence for evolution will take a lot more work.

Has this helped at all?

HBD

ABE: Taq pointed out that indels are not really considered point mutations. For the sake of this post and the types of mutations I am meaning to discuss, I am referring to indels of a single nucleotide only, which could be considered a point mutation, but more technically are not.

Edited by herebedragons, : (*) I meant 3 bases not amino acids

Edited by herebedragons, : No reason given.

Indels are not point mutations.

Yeah, OK. I was thinking about a deletion / insertion of a single base which I would refer to as a point mutation, but you're right, it really isn't.

Codons are a sequence of 3 DNA bases, not amino acids.

Ooppps. That was a "typo"

Thanks

HBD

At least to start with. As Faith has tried to do it is possible (for a time) to avoid "events", "changes" etc. and simply discuss the differences between genomes. The observations of homologs, paralogs etc. can be made without (at first) discussing how those patterns came to be.

I agree with you. The impression that comes with these discussions is often that we start with the assumption of an old earth and evolution. As soon as old ages are mentioned or chimp / human relationship a barrier is immediately put up which makes further discussion very difficult. The point is we should be able to start with the facts and evidence and understand it on its own merit without making evolutionary / old earth assumptions. It is not until AFTER you examine the evidence that the conclusion of evolution and an old earth becomes inevitable.

So, yes, to begin with we need to explain what it is that leads us to come to the conclusions that we do. Not to start with a conclusion and try to prove it.

HBD

There is WAY too much going on in this thread now.

I understand.

it seems you are trying to help with that you've mostly given me more problems to sort out.

If the very basics are giving you more problems, then that is where you should start. The stuff I brought up in my two posts are the kind of things that would be covered in the first week of a genetics course.

I don't think we've got to a point where mutations ought to be the topic.

But that is exactly what you are trying to discuss with Taq. You are putting the horse before the cart. You need to know how mutations can accumulate in a gene and what effect they can have. Without that, it will continue to appear to you that Taq is just using evolutionary assumptions.

Thanks to you and N.Ned at least for agreeing that it is not necessary to use evolutionist language in describing comparisons between species.

Not exactly what I meant. There is hardly any way you can discuss chimp / human relationship without using "evolutionist" language. The reason is that human /chimp relatedness is a conclusion based on the evidence. What you need to learn is why we think those things ARE evidence.

Aaaaagh! Could we please have a moratorium on bringing up anything new on this thread?

Whatever. This is Introduction to Genetics. If you have all the basics down that I put in my post, then fine, I have wasted your time. However, if those principals confuse you, then you should try to grasp them before you move on and try to understand why and how we use genetic similarity to infer relatedness.

HBD

Message 94: ... Not mutations yet, let's just stick to what had already been brought up. ... ANY change to DNA is a mutation, so you are well into mutations already. Baulking at words that describe what you have been describing is not argument but denial.

I know. Let's talk about human / chimp relatedness but don't bring up mutations and don't use evolutionary language. Talk about stacking the deck.

HBD

It does highlight the importance of how we use words and the trouble that brings to these debates. While macroevolution means something specific to you and me, it has completely different implications for creationists. It is also why these debates often end up centering on semantics, because the implications of the words we use are often as important as the definitions themselves. I have been trying to bring it down to basics and try to leave out terminology that could be conflicting, but it is still not much help. People can usually sense when they are being backed into a corner.

HBD

"Macroevolution" is an interpretation, it is not a simple factual description of what has actually occurred.

Personally I don't like to use the words microevolution or macroevolution. I really see no distinction between the two, and using the terms just causes confusion and divisiveness.

"Speciation" is an interpretation, it is not a simple factual description of the fact that a subspecies has simply become unable to interbreed with its parent species. "Divergence" is an interpretation, not a simple factual description of the differences between chimp and human DNA. "Mutation" as used in many contexts is also an interpretation, an assumption, when it implies that it produced all the known functioning alleles.

These terms are all descriptive, not interpretive. When you say that a population splits into two daughter populations that become reproductively isolated, that IS speciation. These two populations diverge, so divergence refers to the process. Mutation describes a change in a DNA sequence. What you take issue with is the implications of those words or processes. And I understand that. I am trying to be "neutral" in my descriptive terms, but sometimes that is just what the words mean.

I was thinking you wanted this thread to go in the direction of comparative genomics - comparing one species to another, which is why my previous posts went in the direction they did. However, it seems as if a better way to go would be to discuss genes, chromosome and alleles. Would you be interested if I posted some introductory material on those topics?

HBD

"Macroevolution" implies that the genome can eventually morph into another kind of genome.

That's exactly what I was saying in my post earlier ... you take issue with the IMPLICATIONS of the words. I totally understand not using the word macroevolution. The other words you mention, speciation, divergence, and mutation ... not so much. It's really hard to expect that people on the science side should change the definitions or their usage of these words to accommodate your ideas (unless you can establish that your ideas SHOULD be accepted). I would also like you to explain why you think they are interpretive; that may help me understand better why you don't want to use those words, because I don't see them as interpretive, but descriptive.

Except they are not speciation events but subspeciation events and nothing has changed in the structure of the genome itself which is what macroevolution requires,

Cough, cough, cough ... more reason why you need some lessons in basic genetics.

AIG has done "extensive research" to determine the Mammalian Ark Kinds. Regarding the dog kind - Canidae, they say:

quote:

---

The strong cognitum and extensive hybrid data suggest the kind is likely at the level of the family.

---

So, let's see if the structure of the genome has changed at all in those subspeciation events by comparing their chromosome numbers. Source

Genus Canis ................................ 78
Genus Otocyon - Bat eared fox .... 72
Genus Vulpes
- Grey fox ................................... 66
- Fennec fox ............................... 64
- Bengal fox ................................ 60
- Kit fox ...................................... 50
- Tibetan sand fox ....................... 36
- Red fox .................................... 34

You don't consider a difference of 44 chromosomes to be a change in the "structure of the genome"? Looks more like a lot of macroevolutionary events, by your own definition, to me. Just within the genus Vulpus there is a large variation in genomic structure. Do you have a different definition of "genomic structure"?

HBD

Oh well, I've struggled along this far with a stacked deck against me ...

I recognize what you are up against. The problem is you are trying to use words in different ways than what is established and then complaining that you are being misunderstood. My comment about "stacking the deck" is only referring to wanting to discuss human / chimp relatedness without using evolutionary terminology or mutations. If you want to talk about how mutations work, or how chromosomes are arranged or how genes function, or the like; those things can be discussed without "evolutionary language."

It also creates confusion when you describe the same basic process but then don't want to apply the accepted term to that process. Example: speciation. You describe a process where a population splits into two reproductively isolated subpopulations, but you don't want to call it speciation. What you are actually disagreeing with is the mechanisms that lead to that event, not the event itself.

Which leads to a question that you missed ...

HBD writes: it seems as if a better way to go would be to discuss genes, chromosome and alleles. Would you be interested if I posted some introductory material on those topics?

It may help you better understand the mechanisms behind the whole process and test your ideas to see they actually work.

HBD

Actually, I had never seen those terms before until creationists started using them as part of their "variation within created kinds" rhetorics. So as far as I know, they're creationist terms anyway!

I did a quick search of this (Wikipedia) and it seems as if the terms were coined back in 1927 by Russian entomologist Yuri Filipchenko (whoever that is?) but fell out of favor when used to describe orthogenetic theories. From there it is not clear how the term began to get used again, but I suspect you are right, that creationists began to use it to differentiate between "acceptable" evolution and "unacceptable" evolution.

So why would a creationist feel compelled to avoid them?

They don't really avoid them, they just make their own definitions. Any evolution that happens is by definition, microevolution. Macroevolution, by definition cannot happen. Even if could be demonstrated that a dog "turned into" a cat ... it would still be just microevolution - by definition.

Personally, how I would LIKE to use the terms is that microevolution is observable, demonstratable change over time. Macroevolution is change that is inferred. I think that puts the two events on different levels of certainty, but doesn't deny that level of change is possible. However, this is unlikely to be accepted in popular verbiage, so I don't try to use it that way.

HBD

I will combine some points from Message 130 in this reply to keep my response on one topic.

As I think I've said somewhere up thread, macroevolution is the only one I really don't want to use.

Fine with me. I won't use it. You may have to accept that others may use the term and you just need to be clear about what they are actually referring to.

I tried to be very clear that I am NOT refusing to use the term "speciation" but that in fact I DO use it BECAUSE I know it would cause confusion not to.

I didn't think you were refusing to use it but were protesting the implications of it. Like this next statement:

"Speciation" implies something other than the usual development of a subspecies, it implies something outside the Kind or Species itself, a step outside

I don't think you mean to suggest that all members of the dog "kind" are all just subspecies, do you? This would require revising taxonomic classifications, which is not really feasible. No, if you were to accept that all extant members of the family Canidae diversified from a single pair of ancestors, then you will just have to accept that that diversity crossed genus and species lines.

But after all this rather rancorous discussion, I think I'm ready to just leave it all alone and struggle through the establishment terms as well as I can.

I understand better what your objections are and will try to do my best to accommodate them.

What you are actually disagreeing with is the mechanisms that lead to that event, not the event itself I certainly don't see how this is true. Population splits are the best example of how new subspecies are formed, and I make a lot of my case about how this leads to decreased genetic variability from this example, so the idea I'm objecting to the mechanisms makes no sense.

Your proposed mechanism for speciation is geographic isolation with a reduction in genetic diversity. It is this reduction in genetic diversity that causes the two populations to be identified and separate species or subspecies. This is not what mainstream thinking proposes.

I AM objecting to the idea that what they lead to is a new "species" rather than just another subspecies. I see no justification for that term since the mechanisms are not different.

We will have to discuss speciation more in depth later on, you do have a different idea of how speciation works (ie. the mechanism).

I might add here that although it hasn't come up in this discussion so far, I've been half expecting someone to question that description and maybe you should since it may not ALWAYS lead to inability to interbreed? Please clarify. If it doesn't, then I don't know what there is to differentiate this new population from any other subspecies.

How to define species is not always straight forward. According to the Biological Species Concept, species are groups of actually or potentially interbreeding natural populations, which are reproductively isolated from other such groups. Although this is a pretty useful definition and probably the most common, there are many cases that just can't be defined in this way.

As I stated in another message Message 366 ... the best way to think about species is that they are distinctive populations of organisms that a separate classification enables more effective communication about that population. Inter-fertility is usually considered a criteria of separating species, but it is not always set in stone.

In other words, when two populations become significantly different from each other and gene flow between those populations is greatly restricted or nonexistent, they probably should be referred to as separate species. Subspecies usually refers to populations that occupy different geographic regions but produce hybrids in nature where their ranges overlap. The two populations usually have distinctive differences so that individuals can be identified as members of their respective populations.

Yes the fox example looks like a lot of change in the structure of the genome, so either that isn't a determinant of a Kind or there is something else in the genomic structure that determines it.

I am not going to advocate that the family Canidae represents the dog kind. I can only go by what the creationist experts say about that. Just know up front that number of chromosomes is not an indication of genetic diversity, but instead, it appears that the genomes have undergone heavy rearrangement. That is something we will have to explore at a later time.

As for going on to discuss genes, chromosomes and alleles, ...The question that I began with was about identifying one species from another genetically.

That is a difficult question to start with. I think I will start a thread on basic genetics and if you want to follow, fine.

HBD

Yes, of course. There's the Kind and then there are subspecies or variations on the Kind.

I realize this is your premise, but it is going to cause a lot of confusion to rewrite taxonomic classifications. It doesn't make sense to call the red fox, domestic dog, and crab-eating fox subspecies of the original created kind (we can call it Canidae originalis ). [ABE]or to have subspecies of subspecies[/ABE] Classifications are for human convenience to facilitate discussion. Grouping organisms into classifications help us better understand what we are talking about.

If you agree that there was an original "ark kind" which then split into two daughter populations, which split again into four daughter populations, etc ... , you will be able to develop a branching cladogram that will look something like this:

You may disagree with the arrangement, but you agree with the basic premise; that the members of the dog kind originated from a common ancestral group, Canidae originalis. Maybe you could propose a very general idea of how you think a tree would look like in you scenario. For example, I would think that the domestic dog would need to branch off very, very early since they have been part of recorded history for many, many years and have undergone heavy breeding. (also keep in mind that the tree shown doesn't include extinct species that are included in Canidae). Then we can apply some tests to your hypothesis to see how well the data supports it.

But if just one allele didn't make it into the new population that's a decrease, and that's very likely to happen with population splits.

A loss of a single allele is not likely to bring about a new subspecies. The situation would be much more complicated than that and require much more significant differences.

I wonder, do you think that two identical populations, if kept geographically isolated could eventually be recognized as separate subspecies? What would be the factors that would bring about that change?

avoid the implication that the Kind can evolve or vary in any way outside the Kind.

We can focus on diversification within the kind.

In order for your hypothesis to gain acceptance you not only need to show evidence that supports it, but you also need to describe what evidence would falsify it. You also need to describe what predictions could be made using this hypothesis. For example, you should be able to arrange all extant canids in a hierarchical pattern based on number of alleles, heterogeneity, number of genes, or some combination of genetic traits. In short, develop a model that explains the data better than the current one.

HBD

By the way, on one level I agree with you that population splits can and do reduce genetic diversity, what I disagree with is that it is the whole story.

Edited by herebedragons, : No reason given.

Well I don't kid myself that anybody is going to accept my view of things to the point that there would be any need to rewrite anything. That would only happen if this creationist view were recognized as true. How soon you think that's going to come about?

Yes, Faith, some will hold on to the ToE as religiously as you hold on to a literal 6 day creation and a global flood and no matter how right you are they will disagree. But the vast majority of us accept the ToE because it is the BEST model we have that can explain the diversity of life. I know it has some flaws, but there is no other model that has been presented that even comes close. If someone presents a model that works better, most of us would adopt it. However, at this point, to get the global scientific community to drastically change paradigms, the evidence would need to be overwhelming, undeniable.

I don't know what all is part of a Kind though.

A major problem for your model. Without a clear and objective way of determining what a "kind" is and what organisms should be included, there is no way to test the model.

Obviously (or maybe not so obviously), a "kind" should be defined as "all organisms, extinct as well as extant, that have diverged through microevolutionary changes from a common ancestral pair (or pairs) that had survived the great flood by being sheltered on the ark."

This definition would generate a branching pattern much like current cladistic analysis do. In fact, unless a different method of generating hierarchical trees is proposed, the trees will look exactly the same. The problem only comes in when the connection is made between "kinds."

This just doesn't reflect the way I think about any of this so I don't know what tests could possibly apply.

I don't see how your proposed model would not generate some kind of hierarchical tree. All these currently living species came from a single mating pair, it would certainly create a branching dendrogram, just like you could trace your family history through a dendrogram.

What is it you object to?

You also need to describe what predictions could be made using this hypothesis. For example, you should be able to arrange all extant canids in a hierarchical pattern based on number of alleles, heterogeneity, number of genes, or some combination of genetic traits. This doesn't fit with my thinking about this.

So what does? How would you propose to arrange the dendrogram of the "dog kind?" What criteria would you use to determine if two species were closely related or more distantly related (within the kind, of course)?

I'd be content for starters if I could just get across this basic scenario I keep describing. .... My argument is that it's the general TREND of all evolutionary processes.

I get what your argument is. What I am trying to explore is whether there is anything to your argument. As I said, on one level you are right, any population split will produce two sub-populations with less genetic diversity (or at most equal but never more). So, can we build a model where the reduction of genetic diversity and shuffling of alleles can account for ALL diversification? Can that model be tested against observable evidence and find support?

You have made an observation (population splits result in reduced genetic diversity) and created an hypothesis (this reduction in genetic diversity and changing allele frequency is sufficient to explain all diversity of life). But in order for this to be accepted as a scientific hypothesis, you can't just stop there. You need a model, you need to make predictions with that model and test those predictions. Otherwise, it is just a fantasy.

HBD

Welcome snapdragon ...

Actually, that is something I am planning to put together and hopefully I will have something up in a couple of days. I will be starting it in a new thread (since you are right, this one is going in a different direction) and I will keep your suggestions for topics in mind as go.

Implicit in the original post's questions are many basic misunderstandings, and they are not and will not be addressed in the direction this thread has progressed.

Agreed!

HBD