Sightings of the revolutionary comet that appeared in the skies of evolutionary biology in 1976—the selfish gene—date back to the 19th and early 20th centuries. It became generally recognized that genes were located on chromosomes and compete with each other in a manner consistent with the later appellation “selfish.” Chromosomes were seen as disruptable by the apparently random “cut and paste” process known as recombination. However, each gene was only a small part of its chromosome. On a statistical basis a (...) gene should escape disruption for many generations. This led George Williams and Richard Dawkins to a new definition of the gene, differing from conventional biochemical definitions in that there were no consistent genic boundaries. There had been no previous sightings of another revolutionary, albeit less verbally spectacular, comet that appeared in 1975—the homostability principle of Akiyoshi Wada. Each gene has a base composition “accent” that distinguishes it from its neighbors. We now see that recombination can be triggered by the shift in base composition at genic boundaries. Hence, the Williams-Dawkins definition approaches the conventional definitions. (shrink)

Eminent scientists are well-placed to bring the novel works of others, even if not in their own areas of expertise, to general attention. In so doing, they may be able to extend original accounts or introduce new terminologies, but they are basically messengers, not innovators. In the 1940s an evolutionary theory of biological aging was explained by Peter Medawar, and informational concepts relating to DNA were explained by Erwin Schrödinger. Both explanations were eventually traced back to the Victorian polymath Samuel (...) Butler—one by Medawar’s research associate Alex Comfort, and the other, albeit indirectly, by Schrödinger himself. In his time Butler’s works were too erudite for general readers and too laden with populist jargon for contemporary experts to take seriously. However, today it appears counterfactually plausible that an early acceptance of his ideas would have greatly quickened the pace of research. (shrink)

Four years after the death of Charles Darwin, his research associate, George Romanes, invoked a mysterious process—“physiological selection”—that could often have secured reproductive isolation independently of, and prior to, natural selection, so leading to an origin of species. This postulate of two sequential selection modes can now be regarded as leading to modern “chromosomal,” as opposed to “genic,” speciation theories. Romanes’ abstractions—which confounded many, but not all, of his contemporaries—equate with divergences in parental DNA sequences that impede meiotic pairing in (...) their hybrid offspring, so rendering that offspring sterile. Unlike Darwin, Romanes saw hybrid sterility as a parental, rather than offspring, phenotype that would, within a species, reproductively isolate certain parents from each other while not impeding their crossing with other parents. This group selection would have empowered natural selection to act more advantageously than in its absence. Given suitable conditions, there could then be divergence from one species into two. The present essay introduces Romanes’ “Physiological Selection; an Additional Suggestion on the Origin of Species” 19:337–411; available as supplementary material in the online version of this essay) for the journal’s “Classics in Biological Theory” collection. (shrink)

Sightings of the revolutionary comet that appeared in the skies of evolutionary biology in 1976—the selfish gene—date back to the 19th and early 20th centuries. It became generally recognized that genes were located on chromosomes and compete with each other in a manner consistent with the later appellation “selfish.” Chromosomes were seen as disruptable by the apparently random “cut and paste” process known as recombination. However, each gene was only a small part of its chromosome. On a statistical basis a (...) gene should escape disruption for many generations. This led George Williams and Richard Dawkins to a new definition of the gene, differing from conventional biochemical definitions in that there were no consistent genic boundaries. There had been no previous sightings of another revolutionary, albeit less verbally spectacular, comet that appeared in 1975—the homostability principle of Akiyoshi Wada. Each gene has a base composition “accent” that distinguishes it from its neighbors. We now see that recombination can be triggered by the shift in base composition at genic boundaries. Hence, the Williams-Dawkins definition approaches the conventional definitions. (shrink)

While its mechanism and biological significance are unknown, the utility of a short mitochondrial DNA sequence as a “barcode” providing accurate species identification has revolutionized the classification of organisms. Since highest accuracy was achieved with recently diverged species, hopes were raised that barcodes would throw light on the speciation process. Indeed, a failure of a maternally donated, rapidly mutating, mitochondrial genome to coadapt its gene products with those of a paternally donated nuclear genome could result in developmental failure, thus creating (...) a post-zygotic barrier leading to reproductive isolation and sympatric branching into independent species. However, the barcode itself encodes a highly conserved, species-invariant, protein, and the discriminatory power resides in the non-amino acid specific bases of synonymous codons. It is here shown how the latter could register changes in the oligonucleotide frequencies of nuclear DNA that, when they fail to match in pairing meiotic chromosomes, could reproductively isolate the parents so launching a primary divergence into two species. It is proposed that, while not itself contributing to speciation, the barcode sequence provides an index of the nuclear DNA oligonucleotide frequencies that drive speciation. (shrink)

The philosopher Ludwig Wittgenstein chose as his prime exemplar of certainty the fact that the skulls of normal people are filled with neural tissue, not sawdust. In 1980 the British pediatrician John Lorber reported that some normal adults, apparently cured of childhood hydrocephaly, had no more than 5 % of the volume of normal brain tissue. While initially disbelieved, Lorber’s observations have since been independently confirmed by clinicians in France and Brazil. Thus Wittgenstein’s certainty has become uncertain. Furthermore, the paradox (...) that the human brain’s information content appears to exceed the storage capacity of even normal-sized brains, requires resolution. This article is one of a series on disparities between brain size and its assumed information content, as seen in cases of savant syndrome, microcephaly, and hydrocephaly, and with special reference to the Victorian era views of Conan Doyle, Samuel Butler, and Darwin’s research associate, George Romanes. The articles argue that, albeit unlikely, the scope of explanations must not exclude extracorporeal information storage. (shrink)

Knowing how introns originated should greatly enhance our understanding of the information we carry in our DNA. Gilbert’s suggestion that introns initially arose to facilitate recombination still stands, though not for the reason he gave. Reanney’s alternative, that evolution, from the early “RNA world” to today’s DNA-based world, would require the ability to detect and correct errors by recombination, now seems more likely. Consistent with this, introns are richer than exons in the potential to extrude the stem-loop structures needed for (...) the homology search that can lead to heteroduplex formation and the recognition of base mismatches. In nucleic acid sequences that were unable concomitantly to encode sufficient stem-loop potential, protein-encoding potential was constrained to arise as segments (exons) interrupted by segments rich in stem-loop potential (introns). Thus, sequences with properties that we now deem intronic are likely to have preceded the emergence of exons. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne’s later hypothesis (1971, European Journal of Immunology 1: 1–9), (...) that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187–198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)

Graphical AbstractMuller found halving gene dosage, as in males with one X chromosome, did not affect specific gene function. Why then was dosage “compensated?” This paradox was solved by invoking collective gene functions such as self/not self discrimination afforded by protein aggregation pressure. This predicts female susceptibility to autoimmune disease.

A biological explanation for the dependence of genome-wide mutation-rate variation on local base context is now becoming clearer. The proportions of G + C relative to A + T—expressed as GC%—is a species-specific DNA character. The frequencies of these single bases correlate with frequencies of corresponding oligonucleotides that are more-sensitive indicators of species specificity. Thus, when k = 3 there are 64 possible trinucleotide sequences and a GC%-rich species has a high frequency of GC-rich 3-mers. Closely related species have similar (...) k-mer patterns. For distantly related species, even if happening to have the same GC% values, k-mer patterns are widely discordant. Conventionally, a base substitution mutation is viewed as a chemical 1-mer phenomenon. However, the selective difference by which the corresponding mutation is scored usually relates to context. Thus, an A to U codon mutation in sickle cell anemia, rather than attracting an anticodon in a structural loop of glutamate tRNA, pairs with the more complementary anticodon loop of valine tRNA. Likewise, a recent statistical analysis of genome-wide mutation-rate variation supports the view that a failure of discordant DNA loops to pair at meiosis can initiate and/or sustain the speciation process. Such disharmony among base patterns may have unknowingly been hinted at by geneticist William Bateson who invoked a music metaphor when considering speciation mechanisms. (shrink)

The view that the initiation of branching into two sympatric species may not require natural selection emerged in Victorian times. In the 1980s paleontologist Stephen Jay Gould gave a theoretical underpinning of this nongenic “chromosomal” view, thus reinstating Richard Goldschmidt’s “heresy” of the 1930s. From modeling studies with computer-generated “biomorphs,” zoologist Richard Dawkins also affirmed Goldschmidt, proclaiming the “evolution of evolvability.” However, in the 1990s, while Gould and Dawkins were recanting, bioinformatic, biochemical, and cytological studies were providing a deeper underpinning. (...) In 2001 this came under attack from leaders in the field who favored Dawkins’ genic emphasis. Now, with growing evidence for the uncoupling of speciation from adaptation, we can reinstate again Goldschmidt’s view and clarify its 19th-century roots. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne's later hypothesis (1971, European Journal of Immunology 1: 1-9), (...) that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187-198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)