Let me add one more comment concerning Avise’s PNAS paper. In the last entry, I focused on his argument that introns counts as evidence against intelligent design. We saw the whole argument fails if we envision design working through evolution. But I want to you to notice something else. In the paragraph preceding the discussion of introns, Avise wrote:
Approximately 1% of all known genes in the human genome encode molecular products that our cells employ to build spliceosomes and conduct splicing operations on premRNA. All this rigmarole has some advantages (e.g., opportunities for alternative splicing during ontogeny and exon shuffling during evolution, both of which can generate functional protein diversity), but such benefits do not come without major fitness costs.
Note that Avise describes alternative splicing as something that confers “some advantage.” Some advantage. As if alternative splicing is just a minor factor in evolution.
Now let’s contrast this to the abstract from a paper by Stephanie Boue, Ivica Letunic, and Peer Bork (Alternative splicing and evolution. BioEssays 2003 25:1031–1034):
Alternative splicing is a critical post-transcriptional event leading to an increase in the transcriptome diversity. Recent bioinformatics studies revealed a high frequency of alternative splicing. Although the extent of AS conservation among mammals is still being discussed, it has been argued that major forms of alternatively spliced transcripts are much better conserved than minor forms.(1) It suggests that alternative splicing plays a major role in genome evolution allowing new exons to evolve with less constraint.
“A major role in genome evolution” sounds a tad more than “some advantage “ to me. In fact, consider the conclusion of Boue et al.:
Recent computational predictions have revealed the high frequency and biological relevance of AS. Some current bioinformatics analyses are now dedicated to discover the benefits of AS for an organism in evolutionary terms, which lead to its spreading. AS thus plays at least two roles. On the one hand, it is a mechanism able to produce in an economical way diversity and specificity at the cell-, tissue- or developmental levels. On the other hand, by decreasing, together with NMD, the selective pressure on genes, it seems to allow a trial/ error approach for the evolution of the gene structure.
Since we’ve already discussed the manner in which alternative splicing allows an organisms to tailor the same genome to the demands of dozens of different, specialized cells, let’s focus on the second role by quoting the authors at length:
Modrek and Lee(1) propose a concept of AS evolution based on the fitness landscape and adaptive walks theory. According to this theory, the fitness of an organism is determined by two factors: the internal state of the organism and the environment in which it lives.
[Pause to make a side point – recall that nudging would exploit the “internal state of the organism.” Thus, nudging would factor into the fitness of an organism.]
The organisms are defined by any two characteristics and placed in a two dimensional plane according to them. Fitness is introduced by turning the surface from a plane into a more rugged landscape with the peaks corresponding to high fitness and the valleys to low fitness. The only way that a population can change its location on the landscape is to have offspring with different genotypes to their parents. However, each step on the landscape has to be uphill in the direction of higher fitness or it would produce organisms less well adapted to their environment with less chance of survival. That is where AS comes into play. If a new exon is incorporated into a gene and alternatively spliced, it would probably first be included in only few of the transcripts and would be free to evolve as the original transcript form would still accomplish its function. In this sense, alternative splicing allows an organism to convert forms with low fitness (inclusion of a new exon) to higher fitness (after accumulation of mutations creating a new useful function). Without AS, those new exons would probably be selected against, lowering the capacity for evolution of an organism. This hypothesis is supported by various types of evidence. Indeed two phenomena are already known to produce new exons that are often alternatively spliced: exon duplication (16,17) and alternative 30 splice site selection within Alu elements.(26) (emphasis added)
Three years later, Ekaterina Ermakova, Ramil Nurtdinov and Mikhail Gelfand (Fast rate of evolution in alternatively spliced coding regions of mammalian genes. BMC Genomics 2006, 7:84). discovered more evidence to support this model:
Overall, this study corroborates the idea that alternative splicing serves as a testing ground for molecular evolution. Several lines of evidence confirm this hypothesis: (i) alternatively spliced isoforms are often evolutionary young both in mammals [2,10] and in insects ; (ii) the rate of nonsynonymous substitutions is higher in alternative regions compared to constitutive ones (this study), (iii) constitutive exons in genes with genome-specific alternative splicing evolve faster than constitutive regions in genes with conserved structure  (cf. a similar observation for duplicated genes [23-25]), (iv) many young (rodent-specific, missing in human and pig as an outgroup) exons are alternatively spliced and tend to have ω>1 in the mouse-rat comparison , and (v) the frequency of nonsynonymous SNPs in human genes is higher in alternative regions than in constitutive regions .
According to this model, alternative splicing is not simply something to offer “some advantage,” but instead plays a key role in helping genomes navigate fitness landscapes. Alternative splicing can allow genomes to effectively hide gene segments from purifying selection, allowing a random search to initiate and proceed – the feelers of evolution. It’s as if genomes must go through a phase that is shielded from selection in order for evolutionary innovations to emerge. And alternative splicing is one significant, all-too-convenient way to purchase that power.
There is a deeper logic to evolution that paying lip service to variations while obsessing about the environment and selection.