So what is the consequence of Avise’s false dichotomy? The bulk of his paper is a detailed exploration of the “outlandish features of the human genome that defy notions of ID by a caring cognitive agent.” While this is an argument that works against design that is coupled to special creation, it fails against design that is coupled to evolution. To see this, let’s pick one of the outlandish features that Avise explores – introns. I chose this example simply because I have already written about it.
Avise’s core argument is as follows:
There are good reasons to think that cells might be better off without introns, in an ideal world.
Let me now add to this argument with the following point:
There are good reasons to think that evolution might be worse off without introns.
In other words, if introns are an “outlandish features of the human genome,” we might also point out that without this outlandish feature, there is no evidence to think that evolution would have cobbled together a human, or human-like, genome.
Recall that I have used the teleological perspective of front-loading to propose a testable hypothesis about introns – they have facilitated the emergence of metazoan-type complexity – that is supported by evidence (here, here, here, and here) and has been successfully defended. (If you have not read these essays, then what follows below will not make much sense to you).
If the design objective is to nudge the emergence of metazoan-type complexity, and not to ensure that cells would be “better off,” then we can see that Avise’s core argument has collapsed.
Nevertheless, let’s have a look at Avise’s reasons.
Introns impose energetic burdens on cells. They are, on average, 30-fold longer than exons and are transcribed into premRNAs before being snipped out; thus, they probably extend the time to produce each mature mRNA by at least 30-fold (compared with the expectation for nonsplit genes).
True. But this is yet another dimension to introns that may have facilitated the emergence of metazoan-type complexity. Ian Swinburne and Pamela Silver (Developmental Cell 14, March 2008), from the Department of Systems Biology at Harvard Medical School, propose that this added time dimension plays a key role in embryological development:
The time taken to transcribe most metazoan genes is significant because of the substantial length of introns. Developmentally regulated gene networks, where timing and dynamic patterns of expression are critical, may be particularly sensitive to intron delays.Werevisit andcomment on a perspective last presented by Thummel 16 years ago: transcriptional delays may contribute to timing mechanisms during development. We discuss the presence of intron delays in genetic networks. We consider how delays can impact particular moments during development, which mechanistic attributes of transcription can influence them, how they can be modeled, and how they can be studied using recent technological advances as well as classical genetics.
And in another research paper (Genes & Development 22:2342–2346) , they write:
Introns may affect gene expression by increasing the time required to transcribe the gene. One way for extended transcription times to affect the behavior of a gene expression program is through a negative feedback loop. Here, we show that a logically engineered negative feedback loop in animal cells produces expression pulses, which have a broad time distribution that increases with intron length. These results in combination with mathematical models provide insight into what may produce the intron-dependent pulse distributions. We conclude that the long production time required for large intron-containing genes is significant for the behavior of gene expression programs.
Our results show that intron length can indeed affect the dynamics of transcriptionally controlled feedback loops; such effects may be important in many contexts, such as somitogenesis during development and responses to immunological signals such as NF-kb.
This all leads to the possibility that introns not only facilitated the emergence of metazoan-type complexity through alternative splicing, but through their ability to modulate feedback loops.
Avise next argues:
Even if time is not important for somatic cells, the metabolic costs of maintaining and replicating all the extra nucleotides in introns must be considerable. To these cellular costs must be added the metabolic expense of making spliceosomes and running the extensive premRNA processing machinery.
I’m not sure just how considerable energetic costs of splicing are to the human body compared to all the other energy costs associated with getting around and thinking. For example, in animals, around 40% of ATP expenditure is used by active transport pumps alone to maintain K+ and Na+ gradients across membranes. Nevertheless, if the metabolic costs of maintaining and replicating all the extra nucleotides in introns must be considerable, you would think there would be a strong selection pressure against introns. And while this doesn’t seem to be the case in metazoans, where introns flourish, it does seem to be the case in single-celled organisms. And this is a pattern that speaks to foresight.
What’s more, we have something of a problem here. Consider the following points:
- Intron-loss has been common in many lineages of unicellular eukaryotes.
- This loss is likely due to selection against introns, as “metabolic costs of maintaining and replicating all the extra nucleotides in introns must be considerable.”
- The last common ancestor of all eukaryotes had a genome rich with introns and a spliceosome much like modern day eukaryotes.
- The last common ancestor of all eukaryotes was likely to be single-celled organism derived from other single celled organisms.
Do you see the problem? If the tendency is for natural selection to strip away introns from single-celled life forms, then why did natural selection work to infuse the last common eukaryotic ancestor with so many introns? And instead of stripping away introns through readily-available and pre-existing mechanisms (retrotransposition and recombination), why did natural selection instead put together the incredibly complex spliceosome to maintain the existence of introns?
Could it be that introns arose during a phase of evolution where natural selection played only a distant role? Could the last common eukaryotic ancestor have been multicellular?
Next, Avise notes
It can also be noted that many organisms (e.g., bacteria) do just fine without split genes and introns, as do the mitochondrial genomes within human cells; thus, there is no universal biological exigency that these features exist.
Exactly. And this is one of the very points that I used to formulate my teleological hypothesis about introns. Introns are not required for cellular life (prokaryotic or eukaryotic), but seem important for the existence of metazoan-type complexity. So this makes for a nice example of the Rabbit/Duck. Avise thinks that many organisms doing just fine without split genes and introns is evidence against design; I have shown that it is evidence that supports design. See how it all depends on context?
Avise adds another reason:
Finally, the human nuclear genome would have ample room to house nonsplit genes for all the proteins it needs (including those that are now alternatively spliced) if an intelligent designer simply would jettison the genome’s junk DNA (see beyond).
I don’t think one person on this planet has ever argued that introns exist because there would be no room in the nucleus for the human genome had they not existed. But is Avise actually suggesting that that a human genome full of nonsplit genes would be better than one full of split genes? That it is better to have 20 genes with 20 associated promoters and transcription factors that make twenty proteins than one gene that makes 20 proteins? Perhaps. For consider his last argument:
Nevertheless, for the sake of argument, let us assume that the metabolic costs imposed by introns are negligible. Do introns otherwise provide evidence of optimal genomic design? No, because premRNA processing also has opened vast opportunities for cellular mishaps in protein production. Such mishaps are not merely hypothetical. An astonishing discovery is that a large fraction (perhaps one-third) of all known human genetic disorders is attributable in at least some clinical cases to mutational blunders in how premRNA molecules are processed (32, 33).
It’s not clear to me that 20 genes with 20 associated promoters and transcription factors that make twenty proteins would be any less vulnerable to mishaps than one gene that makes 20 proteins through alternative splicing. And Avise gives us no reason to think that would be the case.
Nevertheless, for the sake of argument, let us assume that splicing imposed by introns are a needless bug that results in mishaps. Once again, if introns played a key role in the emergence of metazoan-type complexity, by nudging and facilitating the emergence of this complexity, such that this complexity would be significantly less likely to emerge without them, then this bug would be part of the trade-off that is inherent in all designs. So the argument fails once we envision design and evolution working hand-in-hand.