To welcome you back from the holiday season, here are two recent publications of interest, both freely available:
Science, Evolution, and Creationism (NAS)
Evolution and Its Discontents: A Role for Scientists in Science Education
Coalition of Scientific Societies, FASEB Journal 22: 1-4.
The seminar that I give most often when I am invited to speak at other universities begins with a brief introduction to genomes, sets up some comparisons between bacteria and eukaryotes, and then moves into a short overview of bacterial genome size evolution before spending the remainder of the time on genome size diversity and its importance among animals.
The main things that I have to say about bacterial genomes are:
1) Unlike in eukaryotes, bacterial genome size shows a strong positive relationship with gene number (in other words, bacterial genomes contain little non-coding DNA).
Genome size and gene number in bacteria and archaea.2) Bacterial genome sizes do not vary anywhere near as much as those of animals do (on the order of 20-fold versus 7,000-fold).
The diversity of archaeal, bacterial, and eukaryotic genome3) The major pattern in bacteria is that, on average, free-living species have larger genomes than parasitic species which in turn have larger genomes than obligate endosymbionts (Mira et al. 2001; Gregory and DeSalle 2005; Ochman and Davalos 2006).
Genome sizes among bacteria with differing lifestyles.Mira et al. (2001) suggested a different interpretation that is based on two other major processes in evolution — mutation and genetic drift. In terms of mutation, they pointed out that on the level of individual changes that add or subtract relatively small quantities of DNA — i.e., insertions or deletions, or “indels” — deletions tend to be somewhat larger than insertions. The insertions in this case are separate from the addition of whole genes, which happens often in bacteria through sharing of genes among individuals or even across species (“horizontal gene transfer” or “lateral gene transfer“) or gene duplication.
In bacteria (and eukaryotes) small-scale deletions tendSo, on the one hand, there are processes that can add genes (duplication and lateral gene transfer), whereas in the absence of these processes, and if there are no adverse consequences to losing DNA (i.e., there is no selective constraint occurring), genomes should tend to get smaller as a result of this deletion bias. In free-living bacteria, there are many opportunities for gene exchange, with lateral gene transfer adding DNA at an appreciable frequency. Moreover, free-living bacteria tend to occur in astronomical numbers, and elementary population genetics reveals that selection will be strong under such conditions (so that even a mildly deleterious mutation, such as a deletion or disruptive insertion, will probably be lost from the population over time). Finally, free-living bacteria must produce their own protein products, and therefore tend to make use of all their genes, which places selective constraints on changes (including indels) in those sequences.
Endosymbiotic bacteria, especially those that live within the cells of eukaryote hosts, are different in multiple relevant respects. First, they do not regularly encounter other bacteria from whom they can receive genes. Second, they occur in drastically smaller numbers — indeed, they experience a population bottleneck severe enough to shift the balance from selection to drift. Third, they come to rely on some metabolites provided by the host and no longer make use of all their own genes. These factors in combination mean that the selective constraints on many endosymbiont genes are relaxed, and the dominant processes become deletion bias and random drift. Over many generations, endosymbiotic bacteria lose the genes they are not using (and some that are only mildly constrained by selection, such is the strength of drift under such conditions) due to deletion bias, and the end result is highly compact genomes.
The compaction of genomes in endosymbionts can be extreme. The smallest genome known in any cellular organism (except, perhaps, one in Craig Venter‘s lab) is found in the bacterial genus Carsonella, a symbiont that lives within the cells of psyllid insects. It contains only 159,662 base pairs of DNA and 182 genes, some of which overlap (Nakabachi et al. 2006).
Carsonella (dark blue) living within the cells andIn some other bacteria, genes that are not used (including non-functional duplicates) may not be lost for some time and may persist as pseudogenes, just as are observed in large numbers in eukaryote genomes. These tend to undergo additional mutations and to degrade over time but can still be recognized as copies of existing genes. In Mycobacterium leprae, the pathogen that causes leprosy, for example, there are more than 1,100 pseudogenes alongside roughly 1,600 functional genes (Cole et al. 2001). Its genome is about 1 million base pairs smaller than that of its relative M. tuberculosis, but clearly many of the inactive genes have not (yet) been deleted.
The two major influences on bacterial genomes: insertion ofIt would be nice if this post could end there, having delivered a brief overview of an interesting issue in comparative genomics. Sadly, there is more to say because some anti-evolutionists apparently have begun using the topic in a confused attempt to challenge evolutionary science. In particular, though I note that I have become aware of this only second hand, some creationists apparently have suggested that all bacterial genomes are degrading and therefore that bacteria today are simpler than they were in the past, such that complex structures like flagella could not have evolved from less complicated antecedents.
It should be obvious that not all genomes are necessarily “degrading” just because there is a net deletion bias. For starters, selective constraints prevent essential genes from being lost by this mechanism in most bacteria. Furthermore, there exist well established mechanisms that can add new genes to bacterial genomes, including lateral gene transfer and gene duplication. In fact, the rate of gene duplication seems to be related to genome size in bacteria (Gevers et al. 2004). Also, as Nancy Moran noted in an email, “The most primitive bacteria were certainly simple, but they are not around or at least are not easily identified. Many modern bacteria have large genomes and are very complex.” Finally, the compact genomes of endosymbionts, such as in the aphid symbiont Buchnera aphidicola, tend to be more stable than the genomes of free-living bacteria in terms of larger-scale perturbations such as chromosomal rearrangements (Silva et al. 2003).
Some bacteria, in particular those that have shifted to aAs with eukaryotes, the genomes of bacteria provide exceptional confirmation of the fact of common descent. Not only do comparative gene sequence analyses shed light on the relatedness of different bacterial lineages and the evolution of features like flagella, but the presence — and loss to varying degrees — of non-functional DNA highlights a strong historical signal.
Given that it is her work that is being misused by anti-evolutionists, it is fitting that Dr. Moran be given the last word:
“It seems to me that the widespread occurrence of degrading genes, which are present in most genomes including those of animals, plants, and bacteria, argues pretty strongly in favor of evolution. They are the molecular equivalent of vestigial organs.”
Quite right.
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References
Cole, S.T., K. Eiglmeier, J. Parkhill, K.D. James, N.R. Thomson, P.R. Wheeler, and et al. 2001. Massive gene decay in the leprosy bacillus. Nature 409: 1007-1011.
Gevers, D., K. Vandepoele, C. Simillion, and Y. Van de Peer. 2004. Gene duplication and biased functional retention of paralogs in bacterial genomes. Trends in Microbiology 12: 148-154.
Gregory, T.R. 2005. Synergy between sequence and size in large-scale genomics. Nature Reviews Genetics 6: 699-708.
Gregory, T.R. and R. DeSalle. 2005. Comparative genomics in prokaryotes. In The Evolution of the Genome, ed. T.R. Gregory. Elsevier, San Diego, pp. 585-675.
Mira, A., H. Ochman, and N.A. Moran. 2001. Deletional bias and the evolution of bacterial genomes. Trends in Genetics 17: 589-596.
Nakabachi, A., A. Yamashita, H. Toh, H. Ishikawa, H.E. Dunbar, N.A. Moran, and M. Hattori. 2006. The 160-kilobase genome of the bacterial endosymbiont Carsonella. Science 314: 267.
Ochman, H. 2006. Genomes on the shrink. Proceedings of the National Academy of Sciences of the USA 102: 11959-11960.
Ochman, H. and L.M. Davalos. 2006. The nature and dynamics of bacterial genomes. Science 311: 1730-1733.
Silva, F.J., A. Latorre, and A. Moya. 2003. Why are the genomes of endosymbiotic bacteria so stable? Trends in Genetics 19: 176-180.
From the category of “I couldn’t have said it better myself” comes this post by ERV detailing her version of an Excellent flier on ID Creationism.
Intelligent design proponents claim to base their views entirely on scientific data, and argue that the design perspective is more productive than an evolutionary approach. One area where this is particularly evident is in discussions of “junk DNA”. Indeed, with every new discovery (by evolutionary biologists) that some part of the genome shows signs of function, ID proponents suggest that it is they, and not evolutionary biologists, who predicted from the outset that non-coding DNA would prove to be functional. I won’t repeat the discussion of why it is incorrect to suggest that most biologists have stubbornly refused to consider functions for non-coding DNA (see here and here). Instead, what I want to do is to give ID proponents an opportunity to show that their perspective really is scientific and that it can lead to a better description and explanation for biological phenomena than evolutionary science can.
Here is what ID proponents need to do:
1) Specify the basis for assuming that all non-coding DNA must be functional. This makes implicit assumptions about the designer and the design process (namely, that he/she/it would not produce non-functional features of organisms). This assumption must be justified. It also opens the discussion to more philosophical questions, such as why the designer would choose to design such a massive number of pathogens and parasites. Either one can know the designer’s plan or one cannot; if the former, then the way that one would come to know this must be explicated.
2) Specify how one would go about demonstrating evidence of functions for non-coding DNA in the absence of a framework based on common descent. To date, most evidence for function comes from demonstrations of conservation of non-coding sequences, which indicates that constraints imposed by natural selection have maintained these sequences over long spans of evolutionary time. ID would need to propose a testable means of identifying functional sequences that does not rely on the assumption of common descent. Also, it should be recalled that, at present, there is suggestive evidence that about 5% of the human genome is functional. It will be necessary to specify how function will be demonstrated in the other 95% of the genome.
3) Make specific predictions about what function(s) all non-coding DNA is likely to be fulfilling, and propose ways to test those predictions. A vague prediction that all non-coding DNA will prove to be functional is not useful. Moreover, strict Darwinian theory in which natural selection is assumed to remove any non-functional features makes exactly the same prediction, so this does not distinguish ID from Darwinian theory.
4) Propose functions for transposable elements that take into account their parasitic characteristics (e.g., as disease-causing mutagens) but do not invoke the notion of co-option. There are clear examples of transposable elements (TEs) that are functional, for example as regulatory sequences, in the vertebrate immune system, and in cellular stress response. However, this represents a very small percentage of TEs, most of which are neutral or deleterious in the genome. The evolutionary explanation is that, in some relatively rare cases, these former parasites have become integrated into the functional system of the genome. This process of co-option of function is the same process that evolutionary biologists use in explanations of the evolution of complex structures such as eyes or flagella. If co-option is ruled out a priori, then it cannot be used to explain the acquisition of function of formerly parasitic elements and a different explanation must be provided.
5) Provide a specific explanation for how the great majority of transposable elements in the human genome can be functional while showing clear signs of being inactive. Most TEs in the human genome have experienced mutations in regions that render them incapable of undergoing transposition. Many are so degraded by mutation as to be hardly recognizable. How these highly mutated elements carry out a specific function needs to be explained.
6) Provide an explanation for why the DNA sequences of non-coding regions in different species appear to correspond to degree of relatedness. If species do not share common ancestors, then an alternate explanation is required for why species that are claimed to be close relatives exhibit similar sequences whereas those that are claimed to be more distant relatives possess DNA sequences that are not as similar.
7) Propose a testable explanation for why similar species may have widely different quantities of non-coding DNA in their genomes. A simple example is provided by onions and members of the same genus.
8) If one does accept common descent, propose a testable explanation for how there can be significant reductions in DNA content in some lineages. There is evidence that many lineages have experienced losses of non-coding DNA. For example, the evolution of saurischian dinosaurs appears to have included a reduction in DNA amount. How this loss of DNA could occur requires explanation under the assumption that all non-coding DNA in the ancestor’s genome was functional.
More could be added to such a list, but I suspect that this will be enough to provide ID proponents with a prime opportunity to demonstrate their scientific credibility.
So, I have recently become aware that Genomicron is cited on an intelligent design wiki entry for “junk DNA“. They quote two paragraphs from my post A word about “junk DNA”. Specifically, a paragraph in which I critique the term “junk DNA” as unnecessarily implying non-function for all non-coding DNA, and a paragraph in which I list many (unsubstantiated) hypotheses about universal functions for non-coding DNA. Here are two paragraphs from the post that they don’t quote:
To satisfy this expectation, creationist authors (borrowing, of course, from the work of molecular biologists, as they do no such research themselves) simply equivocate the various types of non-coding DNA, and mistakenly suggest that functions discovered for a few examples of some types of non-coding sequences indicate functions for all (see Max 2002 for a cogent rebuttal to these creationist confusions). Case in point: a few years ago, much ado was made of Beaton and Cavalier-Smith’s (1999) titular proclamation, based on a survey of cryptomonad nuclear and nucleomorphic genomes, that “eukaryotic non-coding DNA is functionalâ€. The point was evidently lost that the function proposed by Beaton and Cavalier-Smith (1999) was based entirely on coevolutionary interactions between nucleus size and cell size.
…
Does non-coding DNA have a function? Some of it does, to be sure. Some of it is involved in chromosome structure and cell division (e.g., telomeres, centromeres). Some of it is undoubtedly regulatory in nature. Some of it is involved in alternative splicing (Kondrashov et al. 2003). A fair portion of it in various genomes shows signs of being evolutionarily conserved, which may imply function (Bejerano et al. 2004; Andolfatto 2005; Kondrashov 2005; Woolfe et al. 2005; Halligan and Keightley 2006). On the other hand, the largest fraction is comprised of transposable elements — some of which become co-opted by the host genome, some of which play major role in generating genomic variation, some of which may be involved in cellular stress response, and yet others of which remain detrimental to host fitness (Kidwell and Lisch 2001; Biémont and Vieira 2006). The upshot is that some non-coding DNA is most certainly functional — but when it is, this usually makes sense only in an evolutionary context, particularly through processes like co-option. More broadly, those who would attribute a universal function for non-coding DNA must bear the following in mind: any proposed function for all non-coding DNA must explain why an onion or a grasshopper needs five times more of it than anyone reading this sentence.
Funny that my post Function, non-function, some function: a brief history of junk DNA, in which I discuss how anti-evolutionists are wrong about the history and the science of non-coding DNA, is not quoted.
Here’s a quote they are welcome to use: Simply saying “junk DNA will turn out to have a function” is not a scientifically actionable prediction unless you specify what that function will be and a way to test the proposed function.
It is commonly suggested by anti-evolutionists that recent discoveries of function in non-coding DNA support intelligent design and refute “Darwinism”. This misrepresents both the history and the science of this issue. I would like to provide some clarification of both aspects.
When people began estimating genome sizes (amounts of DNA per genome) in the late 1940s and early 1950s, they noticed that this is largely a constant trait within organisms and species. In other words, if you look at nuclei in different tissues within an organism or in different organisms from the same species, the amount of DNA per chromosome set is constant. (There are some interesting exceptions to this, but they were not really known at the time). This observed constancy in DNA amount was taken as evidence that DNA, rather than proteins, is the substance of inheritance.
These early researchers also noted that some “less complex” organisms (e.g., salamanders) possess far more DNA in their nuclei than “more complex” ones (e.g., mammals). This rendered the issue quite complex, because on the one hand DNA was thought to be constant because it’s what genes are made of, and yet the amount of DNA (“C-value”, for “constant”) did not correspond to assumptions about how many genes an organism should have. This (apparently) self-contradictory set of findings became known as the “C-value paradox” in 1971.
This “paradox” was solved with the discovery of non-coding DNA. Because most DNA in eukaryotes does not encode a protein, there is no longer a reason to expect C-value and gene number to be related. Not surprisingly, there was speculation about what role the “extra” DNA might be playing.
In 1972, Susumu Ohno coined the term “junk DNA“. The idea did not come from throwing his hands up and saying “we don’t know what it does so let’s just assume it is useless and call it junk”. He developed the idea based on knowledge about a mechanism by which non-coding DNA accumulates: the duplication and inactivation of genes. “Junk DNA,” as formulated by Ohno, referred to what we now call pseudogenes, which are non-functional from a protein-coding standpoint by definition. Nevertheless, a long list of possible functions for non-coding DNA continued to be proposed in the scientific literature.
In 1979, Gould and Lewontin published their classic “spandrels” paper (Proc. R. Soc. Lond. B 205: 581-598) in which they railed against the apparent tendency of biologists to attribute function to every feature of organisms. In the same vein, Doolittle and Sapienza published a paper in 1980 entitled “Selfish genes, the phenotype paradigm and genome evolution” (Nature 284: 601-603). In it, they argued that there was far too much emphasis on function at the organism level in explanations for the presence of so much non-coding DNA. Instead, they argued, self-replicating sequences (transposable elements) may be there simply because they are good at being there, independent of effects (let alone functions) at the organism level. Many biologists took their point seriously and began thinking about selection at two levels, within the genome and on organismal phenotypes. Meanwhile, functions for non-coding DNA continued to be postulated by other authors.
As the tools of molecular genetics grew increasingly powerful, there was a shift toward close examinations of protein-coding genes in some circles, and something of a divide emerged between researchers interested in particular sequences and others focusing on genome size and other large-scale features. This became apparent when technological advances allowed thoughts of sequencing the entire human genome: a question asked in all seriousness was whether the project should bother with the “junk”.
Of course, there is now a much greater link between genome sequencing and genome size research. For one, you need to know how much DNA is there just to get funding. More importantly, sequence analysis is shedding light on the types of non-coding DNA responsible for the differences in genome size, and non-coding DNA is proving to be at least as interesting as the genic portions.
To summarize,
I realize that this will have no effect on the arguments made by anti-evolutionists, but I hope it at least clarifies the issue for readers who are interested in the actual science involved and its historical development.
I am not interested in engaging in debates with anti-evolutionists, though I am well aware of their key arguments. The big one, of course, is “irreducible complexity” — traits or features that supposedly could not have evolved because there is no conceivable function for their parts individually nor for a subset of their parts collectively. The bacterial flagellum apparently is the ultimate example of this, which explains why this microscopic protein “motor” can drive an entire philosophical argument along these lines.
I think Darwin said it best (as he often did) in 1871: “Ignorance more frequently begets confidence than does knowledge; it is those who know little, and not those who know much, who so positively assert that this or that problem will never be solved by science.”
There is little concern among biologists that the evolution of bacterial flagella will be worked out, just as a tremendous amount of information is now available about the evolution of eyes (the previous Paleyan example of a supposedly un-evolvable structure).
Last year, Pallen and Matzke (2006) presented a discussion of how bacterial flagella may have evolved, based in large part on comparisons of sequences from the various protein components. Many of the proteins that make up a flagellum have homologues that serve non-flagellar functions, strongly suggesting that they were co-opted from pre-existing proteins during the evolution of flagella. (See Matzke’s detailed model of flagellar evolution here and a video based on it here, and Ken Miller talking about flagella here). Specifically, there is ever-mounting evidence that bacterial flagella and the type III secretory system (TTSS) that toxic bacteria use to inject their prey are descended from the same ancestral structure. The fact that the TTSS lacks many of the proteins in flagella but remains functional (for toxin injection rather than locomotion) clearly indicates that not all the parts need to be present for some function to be carried out by the structure.
Pallen and Matzke (2006) noted that further comparisons of complete genome sequences (hence the post on this blog) would reveal additional insights into the evolution of flagella. Enter Liu and Ochman (2007) from the next issue of PNAS.
Liu and Ochman (2007) examined complete genome sequences from 41 species of bacteria with flagella, and were able to identify a core set of 24 proteins common to all of them, which was present in a very early ancestral bacterium. Not only this, but the core genes appear to be the product of multiple rounds of duplication and diversification, perhaps of one original precursor gene.
The gist of the story is that 1) some genes involved in the construction of flagella in modern bacteria are clearly co-opted from pre-existing genes that were doing something else in the cell (Pallen and Matzke 2006) and 2) a core of about two dozen genes common to all flagellated bacteria (and presumably found in their common ancestor) is the product of duplication and divergence whose reconstructed history agrees very well with the presumed evolutionary relationships among bacteria (Liu and Ochman 2007).
This just goes to show the usefulness of genome data for addressing questions that, for the reason outlined by Darwin, seem unanswerable to some. It also opens the door to some exciting future work.
I asked Howard Ochman what he thought the next key steps will be in this line of study. As he put it, “Naturally we would like to know the function of the structures that were specified by the ancestral set of flagellar genes, and how/why these genes remained functional through their successive duplications. We just completed a companion paper on the bacterial flagellar genes that arose later, and we are now branching out in into the other domains of life.”
I will positively assert, out of optimism rather than ignorance, that many more important insights will be forthcoming from these investigations.
(Update: Nick Matzke is very critical of the paper. He also has posted an updated critique that focuses more on the data.)
(Another update: See Carl Zimmer’s post about blogging as scientific debate).
(And yet another update: A complex tail, simply told at ScienceNOW)
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References
Aizawa, S.-I. 2001. Bacterial flagella and type III secretion systems. FEMS Microbiology Letters 202: 157-164.
Blocker, A., K. Komoriya, and S.-I. Aizawa. 2003. Type III secretion systems and bacterial flagella: insights into their function from structural similarities. Proceedings of the National Academy of Sciences of the USA 100: 3027-3030.
Gophna, U. , E.Z. Ron, and D. Graur. 2003. Bacterial type III secretion systems are ancient and evolved by multiple horizontal-transfer events. Gene 312: 151–163.
Liu, R. and H. Ochman. 2007. Stepwise formation of the bacterial flagellar system. Proceedings of the National Academy of Sciences of the USA 104: 7116-7121.
Matzke, N.J. 2003. Evolution in (Brownian) space: a model for the origin of the bacterial flagellum. Talk.Origins.
Miller, K.R. 2004. The flagellum unspun. In Debating Design: From Darwin to DNA, edited by W. Dembski and M. Ruse. Cambridge University Press, New York, pp. 81-97.
(available online here)
Musgrave, Ian. 2004. Evolution of the bacterial flagellum. In Why Intelligent Design Fails: A Scientific Critique of the New Creationism, edited by M. Young and T. Edis. Rutgers University Press, New Brunswick, NJ.
(available online here)
Nguyen, L., I.T. Paulsen, J. Tchieu, C.J. Hueck, and M.H. Saier. 2000. Phylogenetic analyses of the constituents of Type III protein secretion systems. Journal of Molecular Microbiology and Biotechnology 2: 125–144.
Pallen, M.J., C.W. Penn, and R.R. Chaudhuri. 2005. Bacterial flagellar diversity in the post-genomic era. Trends in Microbiology 13: 143-149.
Pallen, M. J., S.A. Beatson, and C.M. Bailey. 2005. Bioinformatics, genomics and evolution of non-flagellar type-III secretion systems: a Darwinian perspective. FEMS Microbiology Reviews 29: 201–229.
Pallen, M.J. and N.J. Matzke. 2006. From The Origin of Species to the origin of bacterial flagella. Nature Reviews Microbiology 4: 784-790.