Introns Stump Evolutionary Theorists

first_imgThis story is not about Enron and Exxon, but about introns and exons.  The proportions of the scandals they are causing in evolutionary theory, however, may be comparable.    Introns are spacers between genes.  For several decades now, it has been a puzzle why they are there, and why a complex machine called a spliceosome takes them out and joins the active genetic parts – the exons – together. Only eukaryotes have spliceosomes, though; mitochondria have “group II introns” and some mRNAs may have them.  Their presence and numbers in various groups presents a bewildering array of combinations.  Figuring out a phylogenetic tree for introns has eluded evolutionary geneticists, as has understanding their origin and functions (02/18/2005).  Why do genes come in pieces that have to be reassembled?     William Martin and Eugene Koonin said in Nature1 that “The discovery of introns had a broad effect on thoughts about early evolution.”  Some theories have been falsified, and others remain in the running.  Consider the scope of the problems:A current consensus on introns would be that prokaryotes do indeed have group II introns but that they never had spliceosomes; hence, streamlining in the original sense (that is, loss of spliceosomal introns) never occurred in prokaryotes, although it did occur in some eukaryotes such as yeast or microsporidia.  An expansion of that consensus would be that spliceosomes and spliceosomal introns are universal among eukaryotes, that group II introns originating from the mitochondrion are indeed the most likely precursors of eukaryotic mRNA introns and spliceosomal snRNAs, and that many—conceivably most—eukaryotic introns are as old as eukaryotes themselves.  More recent are the insights that there is virtually no evolutionary grade detectable in the origin of the spliceosome, which apparently was present in its (almost) fully fledged state in the common ancestor of eukaryotic lineages studied so far, and that the suspected source of introns—mitochondria, including their anaerobic forms, hydrogenosomes and mitosomes—was also present in the common ancestor of contemporary eukaryotes (the only ones whose origin or attributes require explanation).    This suggests that intron origin and spread occurred within a narrow window of evolutionary time: subsequent to the origin of the mitochondrion, but before the diversification of the major eukaryotic lineages.  This, in turn, indicates the existence of a turbulent phase of genome evolution in the wake of mitochondrial origin, during which group II introns invaded the host’s chromosomes, spread as transposable elements into hundreds—perhaps thousands—of positions that have been conserved to the present, and fragmented into both mRNA introns and snRNA constituents of the spliceosome.This means that a complex molecular machine, the spliceosome (09/17/2004, 09/12/2002), appeared fully formed almost abruptly, and that the intron invasion took place over a short time and has not changed for hundreds of millions of years.  They submitted a new hypothesis:Here we revisit the possible evolutionary significance of introns in light of mitochondrial ubiquity.  We propose that the spread of group II introns and their mutational decay into spliceosomal introns created a strong selective pressure to exclude ribosomes from the vicinity of the chromosomes—thus breaking the prokaryotic paradigm of co-transcriptional translation and forcing nucleus-cytosol compartmentalization, which allowed translation to occur on properly matured mRNAs only.   (Emphasis added in all quotes.)But this means that the nucleus, nucleolus and other complex structures also had to appear in a very brief period of time.  It means that the engulfed organism that somehow became mitochondria had to transfer its introns rapidly into a genome lacking a nucleus.  It means the nucleus had to evolve quickly to segregate the new mitochondrial genes from the nuclear genes.  A lot had to happen quickly.  “This bipartite cell would not be an immediate success story: it would have nothing but problems instead,” they admitted, but they believed that natural selection would favor the few that worked out a symbiotic relationship with their new invaders.    This is not the end of the problems.  The group II introns would have had to embed themselves with reverse transcriptase and maturase without activating the host’s defenses, then evolve into spliceosome-dependent introns and remain unchanged forever after.  Then those embedded group II introns would undergo mutational decay, interfering with gene expression.  Will this work without some miracles?A problem of a much more severe nature arises, however, with the mutational decay of group II introns, resulting in inactivation of the maturase and/or RNA structural elements in at least some of the disseminated copies.  Modern examples from prokaryotes and organelles suggest that splicing with the help of maturase and RNA structural elements provided by intact group II introns in trans could have initially rescued gene expression at such loci, although maturase action in trans is much less effective than in cis.  Thus, the decay of the maturase gene in disseminated introns poses a requirement for invention of a new splicing machinery.  However, as discussed below, the transition to spliceosome-dependent splicing will also impose an unforgiving demand for inventions in addition to the spliceosome.A spliceosome is not an easy thing to invent; it has five snRNAs and over 200 proteins, making it one of the most complex molecular machines in the cell.  Not only that, they appeared in primitive eukaryotes and have been largely conserved since.  Perhaps the miracles can be made more believable by dividing them into smaller steps:It seems that the protospliceosome recruited the Sm-domain, possibly to replace the maturase, while retaining group II RNA domains (snRNAs) ancestrally germane to the splicing mechanism.  While the later evolution of the spliceosome entailed diversification with the recruitment of additional proteins—leading to greater efficiency—the simpler, ancestral protospliceosome could, in principle, rescue expression of genes containing degenerate group II introns in a maturase-independent manner, but at the dear cost of speed.Will a lateral pass from maturase to incipient spliceosome during a long field run lead to a touchdown?  If a stumbling protospliceosome could survive, in spite of vastly decreased translation rate, it might have been able to run the distance with natural selection’s encouragement, they think.  Players would be falling left and right in this “extremely unhealthy situation,” they say, and “the prospects of any descendants emerging from this situation are bleak.”  How could the game go on, then?  “The only recognizable mechanism operating in favour of this clumsy chimaera is weakened purifying selection operating on its exceptionally small initial population.”  Purifying selection means weeding out losers, not adding new champions.  “Finding a solution to the new problem of slow spliceosomes in the presence of fast and abundant ribosomes required an evolutionary novelty.”    They winnow down the possibilities.  Getting instant spliceosomes smacks too much of an improbable feat.  Getting rid of spliceosomal introns from DNA apparently did not occur.  Their solution?  The invention of the nucleus, where slow spliceosomes could operate without competition from fast ribosomes.    This adds new miracles, however.  The nucleus has highly complex pores that permit only authenticated molecules into the inner sanctum.  They think, however, that it must have happened, somehow: “Progeny that failed to physically separate mRNA processing from translation would not survive, nor would those that failed to invent pore complexes to allow chromosome-cytosol interaction.”  So pick your miracles: since necessity is the mother of invention, “The invention of the nucleus was mandatory to allow the expression of intron-containing genes in a cell whose ribosomes were faster than its spliceosomes.”    The near-miraculous arrival of the nucleus is underscored by other feats it performs: “In addition to splicing, eukaryotes possess elaborate mRNA surveillance mechanisms, in particular nonsense-mediated decay (NMD), to assure that only correctly processed mature mRNAs are translated, while aberrant mRNAs and those with premature termination codons are degraded.”  How could this originate?  Again, necessity must have driven the invention: “The initial intron invasion would have precipitated a requirement for mechanisms to identify exon junctions and to discriminate exons (with frame) from introns (without frame), as well as properly from improperly spliced transcripts.  Thus, NMD might be a direct evolutionary consequence of newly arisen genes-in-pieces.”  But then, if it is verified that some translation occurs in the nucleus, that would be “difficult to reconcile with our proposal.”    They ended with comparing their hypothesis with others.  “Our suggestion for the origin of the nucleus differs from previous views on the topic,” they boasted, “which either posit that the nuclear membrane was beneficial to (not mandatory for) its inventor by protecting chromosomes from shearing at division, or offer no plausible selective mechanism at all.”  At least theirs is simpler and includes some requirements to select for the cells with the best inventors – or the ones with the luckiest miracles.1Martin and Koonin, “Hypothesis: Introns and the origin of nucleus-cytosol compartmentalization,” Nature 440, 41-45 (2 March 2006) | doi:10.1038/nature04531.Was any of this storytelling useful?  The shenanigans they pulled, couched in biochemical jargon, can be summarized by two principles in their own imaginations: (1) since the cell needed these superbly-crafted machines, it had to invent them somehow, and (2) since evolution is a fact, it had to happen somehow.  Do you catch any hint of a mechanism for actually inventing a 200-protein supermachine that would actually work?  Did you find any hint that any cell any time had a “protospliceosome” that only worked half-way?  All this was pure fiction built on childlike faith in evolution.    Presenting a hypothesis in science is fine, but how would they ever test something like this?  They offered a few tests that could discriminate between their just-so story and other just-so stories, but nothing that could explain how a spliceosome, or a nuclear membrane with its elaborate pore complexes, or nonsense-mediated decay could have been invented from scratch just because a cell needed these things.    Would that evolutionists would get off this storytelling kick and do something useful with their lives.  Let’s find a cure for cancer.  Let’s find better sources of energy, and think of ways to reduce risks of disease and terrorism, and use science to improve our lives and our world.  Stringing together uncooperative data into a fictional account of prehistory will accomplish nothing and is wasting time and money in a world desperately in need of the productive possibilities of true science.(Visited 10 times, 1 visits today)FacebookTwitterPinterestSave分享0last_img

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