Lamarckian Illusions
Authors: Adam Weiss
Journal: Trends in Ecology & Evolution (2015)

In recent years the term ‘Lamarckian evolution’ has become a household name for processes that do not follow classical Mendelian pattern of inheritance, and it is seen as a relevant complement to Darwinism. In this article I argue that bringing back Lamarck is unjustified and misleading. In recent years the term ‘Lamarckian evolution’ has become a household name for processes that do not follow classical Mendelian pattern of inheritance, and it is seen as a relevant complement to Darwinism. In this article I argue that bringing back Lamarck is unjustified and misleading. Darwinism has been under constant scrutiny ever since On the Origin of Species was published. The theory of evolution by natural selection, based on variation and selection, provided a hitherto unparalleled explanation of life's diversity and change, invoking no forces other than simple biological ones, such as heredity and mutation. Among recurrent themes in the disputes over Darwinism, Lamarckism holds a prominent place. Based on ideas of Darwin's predecessor Jean-Baptiste Lamarck, published in Zoological Philosophy, Lamarckism offers a different view of organismal change based on an intrinsic drive towards higher complexity – the ‘power of life’ – and an ability of the organism to directly respond to the environment, and pass the changed characters on to the next generation – the inheritance of acquired traits (IAT). IAT was widely dismissed by geneticists of the 20th century, but in recent decades research in the field of epigenetics has shown that it does exist in some species, and it has been dubbed ‘Lamarckian heredity’. Although a clear misnomer [1Burkhardt R.W. Lamarck, evolution, and the inheritance of acquired characters.Genetics. 2013; 194: 793-805Crossref PubMed Scopus (78) Google Scholar], it is not the focus of this article. Epigenetics and other discoveries in molecular biology have led some scientists to revive ‘Lamarckian evolution’ and call for a paradigm shift in evolutionary biology. It has been claimed that ‘Lamarckian evolution is reality rather than myth’ [2Koonin E.V. Calorie restriction à Lamarck.Cell. 2014; 158: 237-238Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar], and that ‘the reality of full-fledged Lamarckian evolution...has been convincingly demonstrated’ [3Koonin E.V. Does the central dogma still stand?.Biol. Direct. 2012; 7: 27Crossref PubMed Scopus (47) Google Scholar]. Here I argue that these statements are false. I discuss, as an example, a phenomenon that has been used widely as evidence for Lamarckian evolution, the CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes. Modern physics views Newtonian mechanics as an approximation that holds at low speeds but fails to accurately describe physical relations between objects at speeds close to that of light. By analogy, regarding organisms as units of evolution is an approximation that does not hold at the microbial and molecular scales, where a gene-centered perspective must be adopted to fully explain certain events. The reason is that, in prokaryotes, genetic material is exchanged constantly via horizontal gene transfer (HGT), and microbial populations can thus be viewed as a melting pot for genes and mobile portions of genomes. This type of environment sometimes favors selfish genetic elements that can spread at the expense of the rest of the genome. After all, bacterial viruses (phages) are such mobile elements that travel between cells in specialized protein coats they encode. Recently, a remarkable defense mechanism, termed CRISPR, was discovered that genomes employ to protect themselves from phages and other selfish DNA (Box 1). A number of researchers claimed that CRISPR is a Lamarckian process (e.g., [4Koonin E.V. Wolf Y.I. Is evolution Darwinian or/and Lamarckian?.Biol. Direct. 2009; 4: 42Crossref PubMed Scopus (196) Google Scholar, 5Haerter J.O. Sneppen K. Spatial structure and Lamarckian adaptation explain extreme genetic diversity at CRISPR locus.MBio. 2012; 3: e00126-e212Crossref Scopus (38) Google Scholar, 6Barrangou R. Marraffini L.A. CRISPR-cas systems: prokaryotes upgrade to adaptive immunity.Mol. Cell. 2014; 54: 234-244Abstract Full Text Full Text PDF PubMed Scopus (514) Google Scholar, 7Cooper E.L. Overstreet N. Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems.Phys. Life Rev. 2014; 11: 113-134Crossref PubMed Scopus (16) Google Scholar] and subsequent discussion), in the sense that (i) a mutation, acquired during the lifetime of an individual cell, is non-random, elicited by a specific environmental factor (phage infection), and inherited – in short, IAT; (ii) the mutation is adaptive.Box 1Mechanism of CRISPR ImmunityThe CRISPR (clustered regularly interspaced short palindromic repeats) system is based on a composite locus, wherein one portion encodes Cas (CRISPR-associated) proteins that execute the ‘immune’ response, and the other portion consists of repeat sequences interspaced by short stretches of phage or plasmid origin (spacers). Upon entry of foreign DNA into the cell, it is recognized by the Cas machinery, and a short piece (protospacer) is incorporated into the CRISPR array. The whole array is then transcribed, and the CRISPR RNA is used during subsequent infections as a guide to complementary regions in phage DNA, thereby targeting it for destruction. To distinguish phage from chromosomal DNA during the acquisition of spacers and particularly during the interference phase, a 2–5 nt protospacer adjacent motif (PAM) must be recognized in the foreign DNA. The CRISPR (clustered regularly interspaced short palindromic repeats) system is based on a composite locus, wherein one portion encodes Cas (CRISPR-associated) proteins that execute the ‘immune’ response, and the other portion consists of repeat sequences interspaced by short stretches of phage or plasmid origin (spacers). Upon entry of foreign DNA into the cell, it is recognized by the Cas machinery, and a short piece (protospacer) is incorporated into the CRISPR array. The whole array is then transcribed, and the CRISPR RNA is used during subsequent infections as a guide to complementary regions in phage DNA, thereby targeting it for destruction. To distinguish phage from chromosomal DNA during the acquisition of spacers and particularly during the interference phase, a 2–5 nt protospacer adjacent motif (PAM) must be recognized in the foreign DNA. The first point exemplifies the fallacy of organism-centered evolution. In microbial populations, HGT (spacer acquisition is a form of HGT) is ubiquitous, and up to 18% of a genome can consist of horizontally acquired genes [8Hacker J. Carniel E. Ecological fitness, genomic islands and bacterial pathogenicity. A Darwinian view of the evolution of microbes.EMBO Rep. 2001; 2: 376-381Crossref PubMed Scopus (445) Google Scholar]. Since HGT often brings about new phenotype, it might seem that IAT is widespread in prokaryotes. Indeed, one could claim that any mutation is an IAT because a mutation generated by replication error cannot be distinguished from one that would arise after taking up a piece of homologous DNA (with one mismatch) and recombining it into the chromosome. As a consequence, the difference between ‘non-random’ IAT and ‘random’ mutagenesis is fuzzy in the microbial world. Discussion of this kind is unnecessary if we assume the gene-centered viewpoint. A gene is the replicator subject to natural selection, and other genes in the genome can be considered its environment. If a gene can proliferate more efficiently by HGT than vertically, it will do so. One can argue that, under some conditions, a protospacer can benefit from acquiring PAM (protospacer adjacent motif, Box 1) and being incorporated into a CRISPR locus, ‘betraying’ its original host, which might be doomed for extinction. It can prosper in the new host being selected for on the basis of new phenotype it acquired in the new genetic context. The second point, namely that mutations in the CRISPR locus are adaptive, is an illusion. First, spacers originate from elements with certain signature properties, such as PAM, no matter whether they present a threat to the cell. Indeed, a plasmid can carry a valuable gene and still be destroyed by CRISPR. Second, it has been shown that 18% of CRISPR-harboring organisms possess at least one self-targeting spacer, and that 0.4% of all spacers are self-targeting [9Stern A. et al.Self-targeting by CRISPR: gene regulation or autoimmunity?.Trends Genet. 2010; 26: 335-340Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar]. These numbers probably dramatically understate the frequency of such ‘accidental’ acquisitions because those that were toxic to the cell did not persist and could not be studied [10Vercoe R.B. et al.Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands.PLoS Genet. 2013; 9: e1003454Crossref PubMed Scopus (244) Google Scholar]. Those that did survive did so only if the (proto)spacers were mutated or upon partial degradation and loss of function of the entire CRISPR locus [9Stern A. et al.Self-targeting by CRISPR: gene regulation or autoimmunity?.Trends Genet. 2010; 26: 335-340Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar]. Moreover, CRISPR has been identified in less than half of prokaryotic genomes studied thus far [11Grissa I. et al.The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats.BMC Bioinformatics. 2007; 8: 172Crossref PubMed Scopus (750) Google Scholar]. It is likely that, for the rest, the acquisition of the locus was not adaptive and they did better without it. Hence, there is nothing a priori adaptive about spacer acquisition – as true Lamarckian evolution would require – it only looks like that with the benefit of hindsight. The whole CRISPR system could evolve because it tends on average to increase the fitness of its host organism – a signature feature of Darwinian evolution. As before, when CRISPR mutations are compared with other forms of HGT, we do not find qualitative differences. HGT, too, can be adaptive in disseminating valuable genes such as antibiotic resistance genes. The difference is quantitative (although we do not know the actual numbers): CRISPR pre-selects from the pool of available mutations on the basis of specific sequence characters in the DNA it interacts with. The way this pre-selection is performed is itself subject to standard Darwinian evolution of the cas (CRISPR-associated) genes (Box 1). It would thus be more accurate to talk about more or less ‘deterministic’ mutagenesis [12Koonin E.V. Wolf Y.I. Evolution of microbes and viruses: a paradigm shift in evolutionary biology?.Front. Cell. Infect. Microbiol. 2012; 2: 119Crossref PubMed Scopus (108) Google Scholar] rather than ‘adaptive’ and ‘Lamarckian’. Scientists are obliged to describe natural phenomena as accurately as possible. It is dangerous to put CRISPR in the context of Lamarckism and adaptive mutation because it immediately brings to mind the invisible ‘power of life’, and thus invites misunderstanding. One of the main ideas that derive from Darwinism – and, in my view, one of the most powerful ideas in the history of science – is that adaptation and design can arise without any such guiding hand. This assertion remains true whether or not the adaptation leads to targeted mutations or other tricks that enhance the plasticity of genes and genomes. Jean-Baptiste Lamarck was a great naturalist of his time. He was a vocal opponent of the immutability of species. He recognized that species change gradually and extremely slowly, and he even made a correct guess about exactly how slowly (he thought in terms of hundreds of millions of years [1Burkhardt R.W. Lamarck, evolution, and the inheritance of acquired characters.Genetics. 2013; 194: 793-805Crossref PubMed Scopus (78) Google Scholar]). We should remember him for the good he contributed to science, not for things that resemble his theory only superficially. Indeed, thinking of CRISPR and other phenomena as Lamarckian only obscures the simple and elegant way evolution really works. I am grateful to Renée Schroeder for support and fruitful discussions, and to the Schroeder lab members Markus Dekens, and Gustav Ammerer for critically commenting on the manuscript. This work was supported by the Austrian Science Fund (FWF grant SFB F4308) and the University of Vienna.