Hi Ace,
Just to clarify a common misconception, it’s constructing the clades based on differences. Those differences in no way need to be new mutations. The actual mutations could have occurred millions of years before the speciation, with the cladogram reflecting different alleles fixed in the different species.
Agreed… Although I didn’t say they were new mutations. I merely said they were mutations - that implies that they could have happened at any point in the past.
Correct. For example, the ancestral species could have had both alleles at 50/50 or 70/30, etc.
Yes, cases like that would lead to false positives due to effects like incomplete lineage sorting. This is why these algorithms usually look for more than a single set of shared mutations and then assign confidence appropriately.
There are other effects as well that can lead to false positives such as back-mutations or coincidence
This is a great post which explains some of these:
I agree. back mutations or reversions are important to understand. This creates systematic errors, because 2 differences are incorrectly scored as 0 differences.
Of course, that systematic error gets swamped out by the massive amounts of data we have, but it can be the reason why 2 dendrograms disagree with each other.
I realize that you didn’t specify new mutations. That point was aimed more at George, who has yet to acknowledge the ratio of new mutations to existing polymorphisms. 
Around 30 to 40k.
www.sciencemag.org
Science 21 December 2012:
Vol. 338 no. 6114 pp. 1587-1593 DOI: 10.1126/science.1230612
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The Evolutionary Landscape of Alternative Splicing in Vertebrate Species
Hi George
Are you claiming that a new complex protein sequence with novel function can form sole through reproduction and recombination? Do you think we need almighty assistance for this?
Both design and common descent can make predictions about data we don’t have.
What we can’t do is show either mechanism working to the point were we can experimentally demonstrate the claims.
What is the point of you adding “sole[y] through” ? Mutations happen throughout the whole arc of existence for genetic material. It can happen during meiosis. It can happen during mitosis. It can happen at the stage of fertilization. It can happen in between these steps due to outside energies impinging on the cell, or within the cell.
And then you have “added” the sentence: “Do you think we need almighty assistance for this?”
Remember… you are discussing this with Theists… Christian Theists. From my own point of view, we need Almighty Assistance for each and every step… for the most part via God’s use of Natural/Lawful Causation. Every once in a while, God might use some miraculous (i.e., non-lawful) process to fine tune or make a major change.
I like to use this example: Some Christians prefer to see God as sending the Dinosaur-killing asteroid to Earth from the very moment of creation. While other Christians prefer to imagine God creating the asteroid in the middle of space (miraculously) and throwing it at Earth on a long-term trajectory. I tend to favor the former scenario more than others… but I’m never surprised when someone suggests this or that step was accomplished through non-lawful (aka Miraculous) intervention.
The event where all these mutations occur is reproduction and recombination. How much, if any, new genetic information can these mutations produce?
Here is the paper that you linked to.
As I suspected, this paper doesn’t ask the all important question which is whether or not these alternative transcripts are functional or spurious.
According to Prof. Moran;
It’s important to emphasize that the products of alternative splicing must be functional because we know that splicing is error-prone and that mispliced, nonfunctional, RNAs will be quite common. Every gene will produce a bunch of these aberrantly spliced variants but that doesn’t mean that every primary transcript is alternatively spliced.
It’s important to distinguish between real functional alternative splicing and junk RNAs that arise from splicing errors. One of the ways to do this is to report on the concentrations of the various transcripts but that’s rarely done in papers that promote alternative splicing
First of all, this paper doesn’t ask whether the alternative transcripts they found are functional and it didn’t look at concentrations of these transcripts.
Many of these transcripts unique to humans might just exist by accident due to simple changes in a single nucleotide.
There was a paper that looked at noisy splicing in 2010 and they found it was incredibly common:
Noisy Splicing Drives mRNA Isoform Diversity in Human Cells
While the majority of multiexonic human genes show some evidence of alternative splicing, it is unclear what fraction of observed splice forms is functionally relevant. In this study, we examine the extent of alternative splicing in human cells using deep RNA sequencing and de novo identification of splice junctions. We demonstrate the existence of a large class of low abundance isoforms, encompassing approximately 150,000 previously unannotated splice junctions in our data. Newly-identified splice sites show little evidence of evolutionary conservation, suggesting that the majority are due to erroneous splice site choice. We show that sequence motifs involved in the recognition of exons are enriched in the vicinity of unconserved splice sites. We estimate that the average intron has a splicing error rate of approximately 0.7% and show that introns in highly expressed genes are spliced more accurately, likely due to their shorter length. These results implicate noisy splicing as an important property of genome evolution.
Also see: The most important rule for publishing a paper on alternative splicing
Hi Bill
New genes do occasionally arise. Not through “reproduction and recombination” as you put it but through mutation and selection.
See Dennis Venema’s post on the Quick Evolution of Nylonase
I would also point you to the many instances of de-novo gene creation that we have discovered:
We have direct evidence of new proteins arising in some populations of fruit flies from bits of DNA that were once non-coding.
These strings of random DNA can be found in other winged insects but it is only in certain species of fruit-fly where certain mutations have happened that have allowed them to start being transcribed and translated.
These genes are called de-novo genes because they don’t seem to have ancestors - they have effectively risen from the ashes that exist due to previous mutations, duplications, infections and rearrangements.
The proteins these de-novo genes form are not entirely well folded. These proteins tend to be short. They tend to be polymorphic (evolution is currently tweaking them and experimenting with different versions of them which are still functional) These proteins are also not well tuned - they don’t seem to be very effective at what they do but they do now do something which is very necessary to the survival of the fly. When some of these genes are knocked out, the fly often dies. This shows us that even though these proteins are new (have arisen recently), aren’t well folded and aren’t fine tuned they are still critical to the survival of the fly.
This doesn’t just happen in some fruit flies - it happens in all animals (including humans) but we know of many examples from fruit flies because of how well they have been studied.
Some of these genes appear to have evolved over about 10 million years.
More reading: The continuing evolution of genes (Carl Zimmer)
New genes arise quickly (Jerry Coyne)
It was once thought proteins must be folded into a delicate, precise 3D structure to work properly, but it now seems many exist in a state of intrinsic disorder, flitting through thousands of different possible conformations, all the while remaining perfectly functional. About half of human proteins have at least one long intrinsically disordered segment, while 10 per cent are disordered from beginning to end
The most common method for the creation of new genes though is through duplication of an existing gene and then subsequent modification. According to a new paper released recently, this precise thing is what may have lead to us having larger brains. A partial duplication of the gene ARHGAP11A occurred about 5 million years ago. This formed a new gene which we have named ARHGAP11B.
ARHGAP11B then underwent a transversion from C->G at a single nucleotide. This single transversion causes 55 nucleotides to be deleted after transcription due to mRNA splicing. This new protein boosts the development of the neocortex by increasing production of basal progenitors (you could think of these as the undifferentiated stem cells which will go on to form the neurons within the cortex).
Not only did this 55 nucleotide deletion prematurely truncate the 5th exon, it also causes a shift in the reading frame which completely scrambles the sixth and last exon.
Humans, Neanderthals and Denisovans all have ARHGAP11B. Chimpanzees (and most other animals) only have ARHGAP11A.
Hi Ace
For the genetic change to be fixed in the organism doesn’t the change have to occur during reproduction?
I stipulate that adaptions can occur through random mutation and natural selection (nylon and other examples) but I don’t agree this can be extrapolated to major innovations. I realize I have the minority position with this view although the minority is growing.
Thank you for citing the paper on splicing changes and evolution of the human brain. This will be very interesting to follow. It is fascinating that you can change splicing with a single base pair substitution.
Hey, Bill… that sentence (highlighted above) is wrong. Mutations happen at any time … at any place.
I explained this in my prior post. And you seem to be totally oblivious to why your sentence is wrong. How did you come to such a constricted conclusion?
No… but it does have to occur in the germline. A mutation within a muscle cell in your heart is not going to be passed on to your offspring for example but a mutation within your testes might be. Human males at age 30 undergo about 400 cell divisions per generation within the germline and females undergo about 30 cell divisions per generation within the germline. The mutation rate in humans has been measured using a number of different techniques and the results tend to group around 100 new mutations per generation (most of these coming from the male germline).
I stipulate that adaptions can occur through random mutation and natural selection (nylon and other examples) but I don’t agree this can be extrapolated to major innovations.
What is a major innovation? The evolution of a new protein with a new function is as major as it gets.
Splicing rules are interesting. In most eukaryotes, depending on the gene, the rule is that introns have to start with a GT and end with an AG.
See here - chapter 10.1.3
In this case, a single mutation changing a C->G prematurely started an intron (because the next nucleotide was T) part way through where exon 5 used to be (shown in red - bottom diagram). This increased the length of the 5th intron by 55 nucleotides resulting in a frameshit. This frameshift caused the final exon (exon 6) to be garbled.
Hi George
I don’t agree. See Ace’s explanation.
Major innovations
-ribosome
-ATP synthase
-electron transport chain
-spliceosome
-nuclear pore complex
-bacteria flagella motor
-chromosome structure
-the brain
-the respiratory system
-the muscle skeletal system
Hi Bill,
None of those arose (poof!) like magic in an instant. Some happened prior too far in the past for us to have the entire transcript, of course. But to take an item from the list which has some explanation in the fossil record, biologists have inferred with high confidence that lungs originally had the function of flotation air sacs in fish.
The evolutionary process of taking one feature and fitting it for another purpose is so common that it has a name: exaptation.
I like Ace’s explanation. Certainly a mutation in a muscle cell is not our concern. But you are being too literal in how you anticipate where mutations can occur.
A] Egg Cell genetic material can be mutated prior to use in conception.
If egg cells are irradiated by radiation while an animal is sleeping … is that mutation during reproduction? Technically, no.
B] Egg Cell genetic material can be mutated in the middle of the conception process.
If an egg and sperm cell are in the middle of fusing together, and a toxin level is a little too high…the process of fusion might be flawed… and that could lead to a mutated gene during reproduction.
C] Egg Cell genetic material can be mutated in the embryo’s ovaries … before the female is even born!
If a female embryo is making egg cells for use when the female is an adult, these egg cells can be inaccurately produced… mutations could occur … and it is well after the reproductive phase of the embryo and well before the reproductive phase of the eventual adult!
Hi Chris
How high of confidence? How many genetic changes were required for this transition? The respiratory system contains matched parts to circulate oxygen to the cells. How would you propose a step by step process transitioned this from water to land?
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