Why do you claim they are not functional? Do you have any evidence that the condition you are showing is true. The evidence I have from cancer research is that splice variants are mission critical to sustaining a health organism and proper embryo development.
It’s not a problem if they are neutral. If they are neutral how did they get fixed in the population? Drift? If they are neutral how do you explain the massive morphological differences?
Oh yea splicing variants oops 
Bill, please read this Sandwalk post and the paper that it’s discussing. The existence of a splice variant is not the same thing as evidence of its functional importance.
I didn’t. I asked for evidence that they are functional since their mere existence is not evidence for function. It is entirely possible for splice variants to lack function.
Which splice variants? How many of them? For which genes? In what way are they important? Your statement is way too vague.
Also, do you think that cancer involves mutations in a whole bunch of genes all at once, producing changes in splice variants throughout the genome? Or, is it more likely that there is a mutation in a handful of genes that have an impact on the expression of many other genes?
There is the possibility of neutral drift. It can also be a hitch hiker effect where a mutation has more than one effect. For example, a mutation in a promoter region causes beneficial upregulation of a gene, but in doing so it also increases the production of a splice variant that has no impact on fitness.
Obviously, if differences in splice variants are not causing the differences in morphology then it must be other differences, such as sequence variation in the major isoform, changes in gene regulation, and so on.
Thanks for the article I will take a close look at it.
Items: 1 to 20 of 7691 From a pubmed search this is the number of papers on alternative splicing and cancer.
Just like trying to understand junk DNA you can get false reads depending at what cellular development stage you measure.
Dave and T it depends on when you measure. Here is an article on mouse heart embryo development.
Abstract
Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between fetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.
Several cancers that I have studied are caused by the up regulation on the WNT pathway. This is an embryonic pathway that is down regulated in healthy mature cells. It can be activated in mature cells by hormone deficiency or mutation.
The question is if AS plays a role embryonic development for all genes or is AS merely a side effect of other processes. As the old saying goes, correlation does not prove causation. There could also be a case where only a relative few splice variants are playing a role while most splice variants don’t have a function.
The question is if AS plays a role embryonic development for all genes or is AS merely a side effect of other processes. As the old saying goes, correlation does not prove causation. There could also be a case where only a relative few splice variants are playing a role while most splice variants don’t have a function.
Sure this is possible but the current evidence (7000 pub med papers) does not support this is a side show. Chimps only share 50% of the splice variants observed in humans. The evidence that splicing is active in embryo development is interesting and may indeed be a cause of morphological diversity.
How so?
You need to define what that means and give some references. Are these differences in sequence, or differences in expression for the same splice variant?
Splicing is active in all cells in all stages of maturation. I have no doubt that some splice variants play a role. The question is how many.
Differences in exon combinations that are observed.
And the references?
The Evolutionary Landscape of Alternative Splicing in Vertebrate Species
Science 21 Dec 2012:
Vol. 338, Issue 6114, pp. 1587-1593
DOI: 10.1126/science.1230612
Bill, can you point to a single instance where Behe describes something OTHER than God’s coordination of EVOLUTIONARY processes?
I havent found a single instance!
Its GOD and Lawful Evolution… period. Full stop.
We would actually have something to talk about if someone could locate such a sample text!
That is an easy one. Most are neutral. What is the problem?
Getting fixed in the population. Whats driving this? Drift alone?
It’s only “drift” from the perspective of human perception.
“Drift” is God’s secret weapon of design!
Yes. Exactly. Drift fixes mutations all on its own. It is just basic math. It would take a miracle for there to be fewer differences than we see.
@Jordan just did a simulation to see it for himself: Mantha: Genetics for Dummies.
I read up on Kimura’s paper on this. If i read him right, for a human population of 10000, approx 99.99% of the mutations in a generation will be lost in 16 or so generations… and around 0.01% will take something like 32000 generations (i.e 640K years for a generation of 20 years) to get fixed? (4Ne, taking effective population as 80% of 10000)
That’s a really slow crawl… and if more than one mutation needs to happen in sequence for a particular CNE/mullers ratchet type scenario, it looks very improbable.