Development and Constraint

Carroll, Sean B.  “Evolution at two levels: on genes and form.”  PLoS Biology 3(7):e245, 1159–1166.  2005.  An essay by the Wisconsin developmental geneticist who did most to popularise evo-devo.  It argues that anatomy evolves mainly through changes in the switches of shared master genes, citing the handful of cases then traced to the gene:  one gain, three losses and one modification.  Mirror:  PMC

1. 1a.

   Page 1162:  “The crucial insight from the evolution of Pitx1, yellow, and Hoxc8 is that regulatory mutations provide a mechanism for change in one trait while preserving the role of pleiotropic genes in other processes. This is perhaps the most important, most fundamental insight from evolutionary developmental biology. While functional mutations in a coding region are usually poorly tolerated and eliminated by purifying selection, even complete loss-of-function mutations in regulatory elements are possible because the compartmentation created by the modularity of cis-regulatory elements limits the effects of mutations to individual body parts.” ↩ ↩ ↩

2. 1b.

   Page 1164:  “I argue that there is adequate basis to conclude that the evolution of anatomy occurs primarily through changes in regulatory sequences.” ↩

3. 1c.

   Page 1161:  “A handful of studies have genetically demonstrated that evolution at particular loci has affected the gain [32], loss [26,27,33], or modification of morphological traits [25].”  Carroll's reference 32 is the maize domestication gene teosinte branched1;  26 and 27 are shavenbaby in flies;  33 is Pitx1 in sticklebacks;  25 is Ultrabithorax and fly leg hairs. ↩

Davidson, Eric H., and Douglas H. Erwin.  “Gene regulatory networks and the evolution of animal body plans.”  Science 311(5762):796–800.  2006.  A short theory paper by Caltech's leading student of embryo gene networks and the Smithsonian's leading Cambrian palaeontologist.  It proposes that developmental networks are layered, that their central "kernels" resist change, and that kernels fixed since before the Cambrian explain why animal phyla have kept their body plans.

1. 2a.

   Page 796, section Abstract:  “Because of the hierarchical organization of developmental GRNs, some kinds of change affect terminal properties of the body plan such as occur in speciation, whereas others affect major aspects of body plan morphology.” ↩ ↩

2. 2b.

   Page 796, section Abstract:  “We identify a class of GRN component, the “kernels” of the network, which, because of their developmental role and their particular internal structure, are most impervious to change. Conservation of phyletic body plans may have been due to the retention since pre-Cambrian time of GRN kernels, which underlie development of major body parts.” ↩ ↩

Heard, Edith, and Robert A. Martienssen.  “Transgenerational epigenetic inheritance: myths and mechanisms.”  Cell 157(1):95–109.  2014.  A review by two leading epigeneticists, one working on mammals and one on plants, of which claimed cases of epigenetic inheritance meet a strict test.  It sets the generation counts needed to rule out direct exposure.  Mirror:  PMC

1. 3a.

   Section Figure 1 legend:  “Only F3 individuals can be considered as true trans-generational inheritance (see Box 1), in the absence of exposure.”  “Only F2 and subsequent generations can be considered for evidence of trans-generational inheritance.” ↩

2. 3b.

   Section Conclusions:  “In mammals epialleles can also be found, but are extremely rare, presumably due to robust germ-line reprogramming. How epialleles arise in nature is still an open question but environmentally induced epigenetic changes are rarely transgenerationally inherited, let alone adaptive, even in plants.” ↩ ↩

Laland, Kevin N. et al.  “The extended evolutionary synthesis: its structure, assumptions and predictions.”  Proceedings of the Royal Society B 282(1813):20151019.  2015.  The extended synthesis's own programme statement by the authors of the 2014 "Yes, urgently" piece, with tables setting its assumptions and predictions against the classical theory's.  It reports no new experiments.  Mirror:  PMC

1. 4a.

   Section Abstract:  “retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution”.  Section 4c:  “In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism–environment complementarity.” ↩

2. 4b.

   Section 6:  “Evolutionary biology has never been more vibrant, and it would be a distortion to characterize it as in a (Kuhnian) state of ‘crisis’.” ↩ ↩

3. 4c.

   Section 5:  “The predictions given in table 3 are all short-term.”  “This is supported by research on colonizing populations of house finches [68], water fleas [132] and sticklebacks [55,133]”. ↩

Klinghoffer, David.  “ID scientist at Royal Society:  "no deep discordance" between neo-Darwinism, extended synthesis.”  Evolution News.  Nov 9, 2016.  A Discovery Institute news post from the meeting's last morning, quoting an email from an unnamed scientist sympathetic to intelligent design who was in the audience.

1. 5a.

   “After two days of this conference, my feeling is that there is not any deep discordance between neo-Darwinists and proponents of the Extended Evolutionary Synthesis.”  “In any case, it seems that no novel mechanisms have been discussed that explain formation of totally novel structures.” ↩ ↩

Müller, Gerd B.  “Why an extended evolutionary synthesis is necessary.”  Interface Focus 7(5):20170015.  2017.  The opening paper of the 2016 Royal Society meeting, by a Vienna theoretical biologist who leads the call for an extended synthesis.  It argues the classical theory works for population change but cannot explain novelty and body plans.  Corrected in 2017 for its reference numbering.  Mirror:  PMC

1. 6a.

   Section 2:  “The theory performs well with regard to the issues it concentrates on”.  “Indeed, the MS theory lacks a theory of organization that can account for the characteristic features of phenotypic evolution, such as novelty, modularity, homology, homoplasy or the origin of lineage-defining body plans.”  Section 5:  “a theory change is not a future goal, but we are in the midst of it”. ↩ ↩ ↩

Peter, Isabelle S., and Eric H. Davidson.  “Evolution of gene regulatory networks controlling body plan development.”  Cell 144(6):970–985.  2011.  A review from Davidson's Caltech laboratory of how developmental gene networks are built and how changes at different levels would change the body.  It restates the kernel idea with the experimental cases behind it.  Mirror:  PMC

1. 7a.

   “These circuits are characterized by extensive feedback wiring, and where tested, interference with expression of any of their genes results in developmental catastrophe. These features, and developmental canalization due to the upstream position of such kernels in the body part GRN, explain their exceptional evolutionary conservation.” ↩

2. 7b.

   “In the absence of Ubx function in T3, what should be the haltere imaginal disc produces a wing, hence Ed Lewis’ famous 4-winged fly”.  “Thus Ubx function is repressive with respect to the wing patterning GRN in the late T3 imaginal disc.” ↩

Davidson, Eric H.  “Evolutionary bioscience as regulatory systems biology.”  Developmental Biology 357(1):35–40.  2011.  An essay by Davidson rejecting classical neo-Darwinism as a model for body-plan evolution.  It explains why modern networks resist change at their upper levels and proposes that the first networks were shallow enough for selection to act on.  Mirror:  PMC

1. 8a.

   Section The significance of crown group dGRN design:  “Thus we can think of a crown group dGRN as an evolutionarily terminal, finely divided, extremely elegant control system that allows continuing alteration, variation, and evolutionary experimentation only after the body plan per se has formed, i.e., in structural terms, at the dGRN periphery, and in developmental terms, late in the process.”  “The basic control features of the initial dGRNs of the Precambrian and early Cambrian must have differed in fundamental respects from those now being unraveled in our laboratories.” ↩

2. 8b.

   Section The significance of crown group dGRN design:  “Deconstructing the evolutionary process by which stem group body plans were stepwise formulated will require us to traverse the conceptual pathway to dGRN elegance, beginning where no modern dGRN provides a model.” ↩

Hoekstra, Hopi E., and Jerry A. Coyne.  “The locus of evolution: evo devo and the genetics of adaptation.”  Evolution 61(5):995–1016.  2007.  A review by two evolutionary geneticists testing evo-devo's claim that switch changes drive the evolution of form.  It finds the genomic evidence thin and the best cases mostly losses, and it is the mainstream critique Meyer quotes.

1. 9a.

   Page 995, section Abstract:  “Genomic studies lend little support to the cis-regulatory theory: many of these have detected adaptation in protein-coding regions, including transcription factors, whereas few have examined regulatory regions.”  “the most widely cited examples of adaptive cis-regulatory mutations focus on trait loss rather than gain, and none have yet pinpointed an evolved regulatory site”. ↩

Meyer, Stephen C.  Darwin's Doubt: The Explosive Origin of Animal Life and the Case for Intelligent Design.  HarperOne, New York.  Paperback, with an epilogue answering critics edition.  2014.  The main intelligent-design book on the origin of the animal phyla.  Chapters 13, 14 and 16 argue from embryology that mutation and selection cannot build body plans.  Meyer directs the Discovery Institute's Center for Science and Culture.

1. 10a.

   Chapter 13, The Origin of Body Plans, section Early-Acting Body-Plan Mutations and Embryonic Lethals:  “developmental biology has shown that mutations affecting body-plan formation expressed early in development inevitably damage the organism.” ↩

2. 10b.

   Chapter 13, The Origin of Body Plans, section Early-Acting Body-Plan Mutations and Embryonic Lethals:  “Or put more succinctly, the kind of mutations we need for major evolutionary change we don’t get; the kind we get we don’t need.” ↩

3. 10c.

   Chapter 13, The Origin of Body Plans, section Early-Acting Body-Plan Mutations and Embryonic Lethals:  “3. Such early-acting mutations of global effect on animal development, however, are those least likely to be tolerated by the embryo and, in fact, never have been tolerated in any animals that developmental biologists have studied.”  The third of Paul Nelson's three premises, as Meyer sets them out. ↩

4. 10d.

   Chapter 13, The Origin of Body Plans, section Developmental Gene Regulatory Networks:  “At the center of this regulatory hierarchy are the regulatory networks that specify the axis and global form of the animal body plan during development. These dGRNs cannot vary without causing catastrophic effects to the organism.”  “Indeed, there are no examples of these deeply entrenched, functionally critical circuits varying at all.” ↩

5. 10e.

   Chapter 16, Other Post-Neo-Darwinian Models, section Major But Not Viable, Viable But Not Major:  “They note, “Genomic studies lend little support to the cis-regulatory theory” of evolutionary change.”  “Hoekstra and Coyne conclude, “There is no evidence at present that cis-regulatory changes play a major role—much less a pre-eminent one—in adaptive evolution.””  The e-book text spaces "cis -regulatory".  The second quotation is not in Hoekstra and Coyne's abstract and was not checked against their body text. ↩

6. 10f.

   Chapter 16, Other Post-Neo-Darwinian Models, section Major But Not Viable, Viable But Not Major:  “As we saw in Chapter 13, the experiments of scientists such as Nüsslein-Volhard and Wieschaus have shown definitively that early-acting body-plan mutations invariably generate embryonic lethals—dead animals incapable of further evolution.” ↩

7. 10g.

   Chapter 13, The Origin of Body Plans, section Early-Acting Body-Plan Mutations and Embryonic Lethals:  “A mutation in the regulatory Ultrabithorax gene (expressed midway in the development of a fly) produces an extra pair of wings on a normally two-winged creature.”  “This “innovation” results in a crippled insect that cannot fly because it lacks, among other things, a musculature to support the use of its new wings.” ↩

8. 10h.

   Chapter 13, The Origin of Body Plans, section Endnote 19:  “A wide range of well-documented cases—including cave animals, island birds and insects, and marine and freshwater fishes—show that many animals will tolerate, or actually thrive, after losing traits to mutation”.  “Clearly, processes that result in a loss of form and structure cannot be credibly invoked to explain the origin of form and structure in the first place.”  Meyer is reporting Paul Nelson's exception to the rule that early-acting mutations are lethal. ↩

9. 10i.

   Chapter 15, The Post-Darwinian World and Self-Organization:  “But all were united by the conviction that the neo-Darwinian synthesis had run its course and that new evolutionary mechanisms were needed to explain the origin of biological form.”  Chapter Prologue:  “Some leading evolutionary biologists, particularly those associated with a group of scientists known as the “Altenberg 16,” are openly calling for a new theory of evolution because they doubt the creative power of the mutation and natural selection mechanism.” ↩

Nelson, Paul, and Jonathan Wells.  “Homology in biology: problem for naturalistic science and prospect for intelligent design.”  Darwinism, Design, and Public Education.  Michigan State University Press, East Lansing.  Edited by John Angus Campbell and Stephen C. Meyer.  2003.  A chapter by two Discovery Institute fellows arguing that shared developmental genes do not explain shared or different anatomy, and that homeotic mutants are not raw material for evolution.

1. 11a.

   Page 309:  “Instead, they appear to be functioning as binary switches between alternate developmental fates, with the information for the resulting structures residing elsewhere.”  Page 318:  “Rather, homeotic mutants are life’s proverbial born losers.” ↩ ↩

Batten, Don.  “Hox (homeobox) genes—evolution's saviour?”  Creation Ministries International.  Feb 11, 2006.  A short web article by a CMI scientist arguing that Hox genes cannot drive evolution because homeotic mutants are malformed.  Its only cited evidence is a 1994 review by the biochemist Christian Schwabe.

1. 12a.

   “Changes to homeotic genes cause monstrosities (two heads, a leg where an eye should be, etc.); they do not change an amphibian into a reptile, for example.” ↩

Wood, Todd Charles.  “The AGEing process:  rapid post-Flood intrabaraminic diversification caused by Altruistic Genetic Elements (AGEs).”  Origins (Geoscience Research Institute) 54:5–34.  2002.  A young-earth model of how created kinds split into many species within centuries after the Flood, by designed mobile DNA that switched genes on and off.  Wood, a creationist biologist then at Bryan College, also shows why the older sorting-of-variation models fall short.  Mirror:  Grisda.org

1. 13a.

   Page 5:  “fulfill three criteria for explaining post-Flood diversification: 1) they permanently alter the genome, 2) their alterations can be gene-specific and beneficial, and 3) their beneficial activity was concentrated in the past.”  The PDF breaks the word gene-specific across a line. ↩

Guliuzza, Randy J., and Phil B. Gaskill.  “Continuous environmental tracking:  An engineering framework to understand adaptation and diversification.”  Proceedings of the Eighth International Conference on Creationism, ed. J. H. Whitmore, 158–184.  Creation Science Fellowship.  2018.  A young-earth model by Randy Guliuzza, a physician and engineer at the Institute for Creation Research, and Phil Gaskill of Cramer Fish Sciences, built on a review of 342 journal articles.  It holds that organisms sense their surroundings and adjust themselves by built-in mechanisms, rather than being sorted by selection.

1. 14a.

   Page 158:  “Adaptation happened largely through regulated gene expression and not gene inheritance, per se.” ↩

2. 14b.

   Page 165:  “It appears that regulated, condition-sensing epigenetic mechanisms also “prime the pump” for specific adaptive variation in offspring.” ↩

3. 14c.

   Page 180:  “The effect was observed to last up to 14 generations.”  From the authors' table, in the entry for Houri-Ze'evi and colleagues 2016. ↩

Hinman, Veronica F., and Eric H. Davidson.  “Evolutionary plasticity of developmental gene regulatory network architecture.”  Proceedings of the National Academy of Sciences 104(49):19404–19409.  2007.  A comparison of the early gene networks of a sea urchin and a sea star from Davidson's laboratory.  A five-gene kernel was the same in both;  almost every link outside it differed.  Mirror:  PMC

1. 15a.

   Section Abstract:  “We show here that the GRN structure upstream and downstream of the conserved network kernel has, by contrast, diverged extensively.”  Section SI Text:  “The surprising fact is that outside of the kernel not one of the genes included in Fig. 5 has all of the same regulatory inputs in the two GRNs.” ↩

Israel, Jennifer W. et al.  “Comparative developmental transcriptomics reveals rewiring of a highly conserved gene regulatory network during a major life history switch in the sea urchin genus Heliocidaris.”  PLoS Biology 14(3):e1002391.  2016.  Gene-activity time courses from egg to larva in two sea urchins of one genus, one with a feeding larva and one that skips it, separated by about five million years on the mainstream clock.  Early patterning differs between them.  Mirror:  PMC

1. 16a.

   Section Introduction:  “In particular, key patterning mechanisms such as dorsoventral axis specification, the establishment of the primary signaling center of the embryo, and early cell fate specification differ between the two species.” ↩

Nüsslein-Volhard, Christiane, and Eric Wieschaus.  “Mutations affecting segment number and polarity in Drosophila.”  Nature 287(5785):795–801.  1980.  The large fruit-fly mutation screen, done at Heidelberg, that found the genes that lay out the larva's segments.  It searched specifically for mutations that kill the embryo and change its segment pattern.

1. 17a.

   Page 795, section Abstract:  “In systematic searches for embryonic lethal mutants of Drosophila melanogaster we have identified 15 loci which when mutated alter the segmental pattern of the larva.” ↩

Nüsslein-Volhard, Christiane.  “The identification of genes controlling development in flies and fishes.”  Les Prix Nobel 1995, 285–306.  Nobel Foundation, Stockholm.  Dec 8, 1995.  The Nobel lecture of the geneticist who led the Heidelberg fly screens and later the Tübingen zebrafish screens.  It explains how the screens were designed and what fraction of fly genes and mutations they could detect.

1. 18a.

   Page 289:  “About 5000 genes mutate to lethality. The number of genes required for fertility is less well defined, but is probably not more than one thousand. However, the total number of genes, defined as transcription units, is much larger, about 20000. This means that in Drosophila the majority of the genes do not have indispensable functions. A large fraction, about one third of all lethal mutations, cause a failure of the embryo to hatch (embryonic lethality), however, only about ten percent of the embryonic lethals show an easily detectable and specific morphological phenotype in the unhatched differentiated larvae.” ↩ ↩

2. 18b.

   Page 290:  “In the Heidelberg screens (9-11), we collected mutants detectable by a distinct and significant deviation from normal patterning of the cuticle. These mutants, after complementation tests, defined about 130 genes, distributed randomly over the three major chromosomes. Using similar scoring criteria, screens for maternal mutants, defining about 30 genes, were performed in several laboratories (12-16).” ↩ ↩

The fly figures are from Nüsslein-Volhard's lecture¹⁸.  5,000 ÷ 20,000 = 25% of genes can mutate to lethality.  One third of 5,000 is about 1,700;  one tenth of that is about 170.  The lecture's fractions are of lethal mutations, not of genes, so the 1,700 and 170 are rough.  The screens found about 130 zygotic and about 30 maternal pattern genes¹⁸, 160 in all.  Wieschaus and Nüsslein-Volhard's 2016 retrospective counts 600 mutants in 120 genes⁷⁷.  The mouse figures are from Dickinson and colleagues²⁰:  410 ÷ 1,751 = 23.4%;  (410 + 198) ÷ 1,751 = 34.7%. ↩

Dickinson, Mary E. et al.  “High-throughput discovery of novel developmental phenotypes.”  Nature 537(7621):508–514.  2016.  The International Mouse Phenotyping Consortium's report on its first 1,751 single-gene knockout mouse lines, bred from carriers and scored for whether, when and how the embryos died.  The largest systematic count of how many mammalian genes are needed for life.  Mirror:  PMC

1. 20a.

   Section Abstract:  “Approximately one third of all mammalian genes are essential for life.”  Section Results:  “We also identified 198 “subviable” lines, defined as fewer than 12.5% (half of expected) homozygous preweaning pups”.  “The vast majority of the alleles employed in this study were of “tm1.1” or “tm1b” IKMC variants, which disrupt the coding sequence (1704 of 1804 unique alleles”. ↩ ↩

2. 20b.

   Section Results:  “a majority of lines (147/242; 60.7%) died prior to E12.5 and a majority of these (107/147; 72.8%), development ceased prior to E9.5, the earliest time point examined.” ↩

Chan, Yingguang Frank et al.  “Adaptive evolution of pelvic reduction in sticklebacks by recurrent deletion of a Pitx1 enhancer.”  Science 327(5963):302–305.  2010.  A study from David Kingsley's Stanford laboratory that found the switch that turns on Pitx1 in the stickleback pelvis, showed it deleted in most pelvis-less populations, tested it in transgenic fish and looked for signs of selection around it.  Mirror:  PMC

1. 21a.

   Section Abstract:  “Although Pitx1 null mutations are lethal in laboratory animals, Pitx1 regulatory mutations show molecular signatures of positive selection in pelvic-reduced populations.” ↩

2. 21b.

   Section Nature of mutations in pelvic-reduced fish:  “Nine of the 13 pelvic-reduced stickleback populations—but zero out of 21 pelvic-complete populations—showed consistent missing genotypes for multiple consecutive SNP markers located in and around the Pel enhancer”.  “The larger genotyping survey identified a total of nine different haplotypes with different staggered deletions, each consistently seen within a pelvic-reduced population, and each overlapping or completely removing the Pel enhancer region (Figs. 4 and S8).” ↩

3. 21c.

   Section Introduction:  “This region contains Pituitary homeobox 1 (Pitx1), a gene expressed in hindlimbs but not forelimbs of many different vertebrates, and required for normal hindlimb development (13).” ↩

4. 21d.

   Section Discussion:  “We hypothesize that sequence features in the Pitx1 locus may predispose the locus to structural changes, possibly explaining the high prevalence of independent deletion mutations fixed in different pelvic-reduced stickleback populations.” ↩

Stern, David L., and Virginie Orgogozo.  “The loci of evolution: how predictable is genetic evolution?”  Evolution 62(9):2155–2177.  2008.  A review by two fly geneticists that compiled all 331 mutations then shown to cause evolved differences in multicellular organisms and counted how many lay in switches and how many in protein-coding sequence.  The authors warn that the sample is biased toward genes people chose to study.  Mirror:  PMC

1. 22a.

   Section Prediction 2 (strength of selection and time scale):  “In contrast, it is striking that only about 7% of comparisons above the species level (five cases out of 75) have so far identified null alleles (Table 4). Instead, studies above the species level have found mostly coding mutations that modify but do not eliminate protein function and cis-regulatory mutations that alter only part of the gene's function (Table 4).” ↩

2. 22b.

   Section Abstract:  “Cis-regulatory mutations currently represent approximately 22% of 331 identified genetic changes although the number of cis-regulatory changes published annually is rapidly increasing. Above the species level, cis-regulatory mutations altering morphology are more common than coding changes.” ↩

3. 22c.

   Section The data:  “Twenty-two percent of mutations in our dataset occurred in cis-regulatory regions for all types of phenotypic change (22% with domesticated examples excluded), and 40% for morphological evolution (55% with domesticated examples excluded).” ↩

4. 22d.

   Section The data:  “Therefore, we cannot estimate, based on our dataset, the real overall frequency of cis-regulatory versus coding mutations causing phenotypic evolution.” ↩

5. 22e.

   Section Appendix 2, on trait losses:  “Finally, the abundance of studies of trait loss observed by Hoekstra and Coyne (2007) may reflect the more mundane fact that when comparing closely related species, where analysis is more straightforward, phenotypic loss is more common than gain (Adamowicz and Purvis 2006).” ↩

Lewis, Edward B.  “A gene complex controlling segmentation in Drosophila.”  Nature 276(5688):565–570.  1978.  The classic genetic study of the fruit fly's bithorax complex, a cluster of Hox genes that set the identity of the thoracic and abdominal segments.  Lewis shared the 1995 Nobel Prize in Physiology or Medicine for this work.

1. 23a.

   Page 565, section Abstract:  “The bithorax gene complex in Drosophila contains a minimum of eight genes that seem to code for substances controlling levels of thoracic and abdominal development.” ↩

Fernandes, Jorge et al.  “Muscle development in the four-winged Drosophila and the role of the Ultrabithorax gene.”  Current Biology 4(11):957–964.  1994.  A study of the flight muscles in the classic four-winged fruit fly, co-authored by Edward Lewis, who first bred it.  The transformed segment grows wings but only rudimentary flight muscles.

1. 24a.

   Page 957, section Abstract:  “In flies that are homozygous for three mutant alleles (anterobithorax, bithorax3, postbithorax) of the Ultrabithorax gene, the third thoracic segment (T3) is transformed towards the second (T2). The adults have two pairs of wings, but the homeotically transformed T3 (HT3) has only rudimentary indirect flight muscles.” ↩

Wells, Jonathan.  Zombie Science: More Icons of Evolution.  Discovery Institute Press, Seattle.  2017.  A book by a Discovery Institute biologist revisiting the textbook examples of evolution he criticised in Icons of Evolution (2000).  It has sections on four-winged flies and on the Hox leg-suppression experiment.

1. 25a.

   Section Four-Winged Fruit Flies:  “But the mutant four-winged fruit fly lost its balancers in the bargain. Worse, the mutant wings do not have any flight muscles.” ↩

Martin, Arnaud et al.  “CRISPR/Cas9 mutagenesis reveals versatile roles of Hox genes in crustacean limb specification and evolution.”  Current Biology 26(1):14–26.  2016.  Gene knockouts and knockdowns of six Hox genes in the amphipod Parhyale hawaiensis, from Nipam Patel's laboratory.  Each produced homeotic changes among the animal's existing limb types.  The knockouts were made in the injected embryos themselves, which are mosaics, not in bred lines.

1. 26a.

   Page 14, section Summary:  “We found that abdominal-A (abd-A) and Abdominal-B (Abd-B) are required for proper posterior patterning, with knockout of Abd-B resulting in an animal with thoracic type legs along what would have been an abdomen, and abd-A disruption generating a simplified body plan characterized by a loss of specialization in both abdominal and thoracic appendages.” ↩

2. 26b.

   Page 24:  “Our functional studies can now point to the shifting domains of Hox genes as part of the basis for crustacean body-plan evolution, but there is no doubt that this will only be part of the explanation.” ↩

Averof, Michalis, and Nipam H. Patel.  “Crustacean appendage evolution associated with changes in Hox gene expression.”  Nature 388(6643):682–686.  1997.  A comparison of where the Hox genes Ubx and AbdA are switched on across several crustaceans.  It is a correlation across living species, not a manipulation.

1. 27a.

   Section Abstract:  “We show here that changes in the expression pattern of the Hox genes Ubx and AbdA in different crustaceans correlate well with the modification of their anterior thoracic limbs into feeding appendages (maxillipeds).” ↩

Gompel, Nicolas et al.  “Chance caught on the wing: cis-regulatory evolution and the origin of pigment patterns in Drosophila.”  Nature 433(7025):481–487.  2005.  Transgenic tests of the switches of the pigment gene yellow in a fly that has gained a male wing spot and in relatives that lack it.  The spot traces to new transcription-factor binding sites in an old switch.

1. 28a.

   Page 481, section Abstract:  “Here we identify one of the molecular mechanisms that contributes to the evolutionary gain of a male-specific wing pigmentation spot in Drosophila biarmipes, a species closely related to Drosophila melanogaster. We show that the evolution of this spot involved modifications of an ancestral cis-regulatory element of the yellow pigmentation gene. This element has gained multiple binding sites for transcription factors that are deeply conserved components of the regulatory landscape controlling wing development, including the selector protein Engrailed.” ↩

Prud'homme, Benjamin et al.  “Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene.”  Nature 440(7087):1050–1053.  2006.  A comparison across a group of fly species in which a male wing spot has come and gone several times, tracing two gains and two losses to the switches of one pigment gene.

1. 29a.

   Page 1050, section Abstract:  “Here we show that a male wing pigmentation pattern involved in courtship display has been gained and lost multiple times in a Drosophila clade. Each of the cases we have analysed (two gains and two losses) involved regulatory changes at the pleiotropic pigmentation gene yellow.”  “Surprisingly, two independent gains of wing spots resulted from the co-option of distinct ancestral CREs.” ↩

Arnoult, Laurent et al.  “Emergence and diversification of fly pigmentation through evolution of a gene regulatory module.”  Science 339(6126):1423–1426.  2013.  A study of how a wing spot first appeared and then diversified in a group of flies.  Several pigment genes came under the control of one regulator, Distal-less, whose own pattern then changed between species.

1. 30a.

   Page 1423, section Abstract:  “Here, we show that a spot of dark pigment on fly wings emerged from the assembly of a novel gene regulatory module in which a set of pigmentation genes evolved to respond to a common transcriptional regulator determining their spatial distribution.” ↩

Koshikawa, Shigeyuki et al.  “Gain of cis-regulatory activities underlies novel domains of wingless gene expression in Drosophila.”  Proceedings of the National Academy of Sciences 112(24):7524–7529.  2015.  Reporter tests of the switches of the signalling gene wingless in a spotted fly and in the laboratory fruit fly.  Three switch activities found only in the spotted fly match its new spots.  Mirror:  PMC

1. 31a.

   Page 7524, section Abstract:  “Our results indicate that one novel domain of wg expression in D. guttifera wings evolved by co-opting pre-existing regulatory sequences governing gene activity in the developing wing.” ↩

Cleves, Phillip A. et al.  “Evolved tooth gain in sticklebacks is associated with a cis-regulatory allele of Bmp6.”  Proceedings of the National Academy of Sciences 111(38):13912–13917.  2014.  Crosses, gene mapping and allele-specific expression tests in a lake stickleback population that has about twice as many throat teeth as marine sticklebacks.  One of the few switch changes linked to a gain rather than a loss of a structure.  Mirror:  PMC

1. 32a.

   Section Abstract:  “Here we show that a derived benthic freshwater stickleback population has evolved an approximate twofold gain in ventral pharyngeal tooth number compared with their ancestral marine counterparts.”  “cis-regulatory changes have elevated the relative expression level of the freshwater benthic Bmp6 allele at late, but not early, stages of stickleback development.” ↩

Frankel, Nicolás et al.  “Morphological evolution caused by many subtle-effect substitutions in regulatory DNA.”  Nature 474(7353):598–603.  2011.  A dissection, letter by letter, of one switch of the gene shavenbaby that changed when larvae of Drosophila sechellia lost most of their fine hairs.  Each substitution's effect was measured in transgenic flies.  Mirror:  PMC

1. 33a.

   Page 598, section Abstract:  “Here we show that the function of one of these enhancers evolved through multiple single-nucleotide substitutions that altered both the timing and level of svb expression.”  “We found that each substitution had a relatively small phenotypic effect, and that many nucleotide changes account for this large morphological difference. In addition, we observed that the substitutions had non-additive effects.” ↩

Rebeiz, Mark et al.  “Stepwise modification of a modular enhancer underlies adaptation in a Drosophila population.”  Science 326(5960):1663–1667.  2009.  A study of a dark-bodied fly population in Uganda that traced its colour to one switch of the pigment gene ebony and ordered the mutations that built the dark allele.  Mirror:  PMC

1. 34a.

   Page 1663, section Abstract:  “We show that at least five mutations with varied effects arose recently from a combination of standing variation and new mutations and combined to create an allele of large phenotypic effect.” ↩

Durrett, Rick, and Deena Schmidt.  “Waiting for two mutations:  with applications to regulatory sequence evolution and the limits of Darwinian evolution.”  Genetics 180(3):1501–1509.  2008.  A population-genetics model, with simulations, of how long it takes for one transcription-factor binding site to be switched off and another switched on, for fly-sized and human-sized populations.  Two Cornell mathematicians wrote it partly to answer Michael Behe.  Mirror:  PMC

1. 35a.

   Page 1501, section Abstract:  “Consistent with recent experimental observations for Drosophila, we find that a few million years is sufficient, but for humans with a much smaller effective population size, this type of change would take >100 million years.” ↩

Irie, Naoki, and Shigeru Kuratani.  “Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.”  Nature Communications 2:248.  2011.  A comparison of gene activity through development in mouse, chicken, frog and zebrafish embryos.  The first measured evidence that the vertebrate pharyngula is the most alike stage.  Mirror:  PMC

1. 36a.

   Section Abstract:  “Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent.” ↩

Kalinka, Alex T. et al.  “Gene expression divergence recapitulates the developmental hourglass model.”  Nature 468:811–816.  2010.  Gene-activity measurements through embryonic development in six fruit-fly species, fitted gene by gene to models of evolution.  Found the middle of development most alike and most constrained by selection.  Mirror:  Publications.mpi-cbg.de

1. 37a.

   Page 811:  “By fitting different evolutionary models to each gene, we show that at each time point more than 80% of genes fit best to models incorporating stabilizing selection, and that for genes whose evolutionarily optimal expression level is the same across all species, selective constraint is maximized during the phylotypic period.” ↩

2. 37b.

   Page 811:  “Darwin (1859) believed this to be the most compelling evidence in favour of common descent, reasoning that adult life-stages will afford the greatest opportunity for natural selection to operate … Despite its intuitive appeal, the principle of early embryonic conservation has not been supported by morphological studies.” ↩

Kalinka, Alex T., and Pavel Tomancak.  “The evolution of early animal embryos: conservation or divergence?”  Trends in Ecology and Evolution 27(7):385–393.  2012.  A review of molecular, network and life-history evidence on how much early animal embryos differ between species.  It concludes they differ a good deal, often as adaptations to different habitats.

1. 38a.

   Section Abstract:  “Here, we focus on early embryonic development and discuss several lines of evidence, from recent molecular data, through developmental networks to life-history strategies, that indicate that early animal embryos are not highly conserved. Bringing this evidence together, we argue that the nature of early development often reflects adaptation to diverse ecological niches.” ↩

Levin, Michal et al.  “The mid-developmental transition and the evolution of animal body plans.”  Nature 531(7596):637–641.  2016.  Gene-activity time courses through embryonic development for species from ten phyla, sampled with one method.  Within a phylum the middle of development is most alike;  between phyla it differs most.  Describes the differences;  does not test how they arose.  Mirror:  PMC

1. 39a.

   Section Main text, closing paragraphs:  “Our results are consistent with an inverse hourglass model for metazoan body plans”. ↩

Galis, Frietson, and Johan A. J. Metz.  “Testing the vulnerability of the phylotypic stage: on modularity and evolutionary conservation.”  Journal of Experimental Zoology 291(2):195–204.  2001.  A survey of published teratology experiments on rodent embryos, asking which stage of development is most easily killed or deformed.  It found the conserved middle stage most vulnerable and blamed the many interactions between tissues at that stage.

1. 40a.

   Page 195, section Abstract:  “A search of the teratological literature shows that disturbances at this stage lead to a much higher mortality than in other stages, in accordance with the prediction.” ↩

Uchida, Yui et al.  “Embryonic lethality is not sufficient to explain hourglass-like conservation of vertebrate embryos.”  EvoDevo 9:7.  2018.  Experiments that disturbed zebrafish, frog and chicken embryos with heat, drugs or ultraviolet-induced mutations at early, middle and late stages, and counted deaths.  A direct test of whether the conserved middle stage is conserved because it is the most fragile.  Mirror:  PMC

1. 41a.

   Section Abstract, Conclusion:  “In opposition to the “mid-embryonic lethality hypothesis,” our results consistently showed that the stage with the highest lethality was not around the conserved pharyngula period, but rather around the early period in all the vertebrate species tested. These results suggest that negative selection by embryonic lethality could not explain hourglass-like conservation of animal embryos.” ↩

2. 41b.

   Section Results, Tracking survival rates following UV irradiation:  “However, reduced survival rates in the UV-irradiated group were detected only around the gastrula and early segmentation periods (from 50%-epiboly to 5-somite stage); no embryonic death was observed in the pharyngula period (from Prim-5 to High-pec).” ↩

Hu, H. et al.  “Constrained vertebrate evolution by pleiotropic genes.”  Nature Ecology and Evolution 1(11):1722–1730.  2017.  A comparison of gene activity from early to late embryos in eight chordates.  It found the conserved middle stage fits vertebrates better than chordates as a whole, and that its genes are the ones most reused elsewhere in development.

1. 42a.

   Section Abstract:  “Furthermore, we found that vertebrates' conserved mid-embryonic developmental programmes are intensively recruited to other developmental processes, and the degree of the recruitment positively correlates with their evolutionary conservation and essentiality for normal development.” ↩

Bergman, Jerry.  “The rise and fall of Haeckel's biogenetic law.”  Creation Research Society Quarterly 37(2):110–122.  Sep 2000.  A creationist history of recapitulation theory that ends with a design explanation for why embryos look alike.

1. 43a.

   Page 120:  “The stages of embryological development of many animals show some similarities but the major reason for this is design constraints. Likewise adult organs show much similarity because only so many ways exist to design a heart or lung, and we would expect the earlier in development the fewer the design possibilities that exist.” ↩

Domazet-Lošo, Tomislav, and Diethard Tautz.  “A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns.”  Nature 468:815–818.  2010.  A study that dated zebrafish genes by how widely they are shared across the tree of life, then weighted each stage of development by the age of the genes it uses.  The dating method assumes the tree it is used to support.

1. 44a.

   Section Abstract:  “Using zebrafish ontogeny and adult development as a model, we find that the phylotypic stage does indeed express the oldest transcriptome set and that younger sets are expressed during early and late development”. ↩

Rechavi, Oded et al.  “Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans.”  Cell 147(6):1248–1256.  2011.  Experiments in roundworms showing that small RNAs made against a virus are passed to offspring that never met the virus, and protect them.  The silencing usually fades in a few generations, with a more stable mode in some lines.  Mirror:  PMC

1. 45a.

   Section Discussion:  “Our results therefore support the Lamarckian concept of the inheritance of an acquired trait.” ↩

2. 45b.

   Section Results:  “This indicates that in addition to the “fading” (~3 generations) mode of silencing that we described above, a second and more stable mode of inherited silencing can also take place.” ↩

Mitchell, Elizabeth.  “Epigenetic changes let mice inherit their fathers' fears.”  Answers in Genesis.  Jan 9, 2014.  A young-earth news commentary on the Dias and Ressler mouse study.  It reads heritable epigenetic marks as designed adaptability and denies they can add new genes.

1. 46a.

   Section God's Design for Keeping Animal Adaptations in the Family?:  “The more we learn about heritable epigenetic modifications, the more apparent is the wisdom of our Creator who may well have designed a way for animals to vary and provide adaptations to their offspring while keeping the genomic information itself intact.” ↩

2. 46b.

   Section Lamarck Revisited?:  “Epigenetic modifications only affect the expression of existing genes and do not add new genes to an organism. Therefore, epigenetics cannot be a mechanism for molecules-to-man evolution.” ↩

Johannes, Frank et al.  “Assessing the impact of transgenerational epigenetic variation on complex traits.”  PLoS Genetics 5(6):e1000530.  2009.  A panel of Arabidopsis lines that differ in DNA methylation but hardly at all in DNA sequence, followed for eight generations to see which marks persist and how much they affect flowering time and height.  Mirror:  PMC

1. 47a.

   Section Abstract:  “The epiRILs showed variation and high heritability for flowering time and plant height (∼30%), as well as stable inheritance of multiple parental DNA methylation variants (epialleles) over at least eight generations.”  Section Discussion:  “about one half of DNA hypomethylation variants induced by ddm1 systematically regain wt DNA methylation over two to five generations”. ↩

Schmitz, Robert J. et al.  “Transgenerational epigenetic instability is a source of novel methylation variants.”  Science 334(6054):369–373.  2011.  Genome-wide methylation maps of Arabidopsis lines grown by single-seed descent for 30 generations, from Joseph Ecker's laboratory at the Salk Institute.  It measured how often methylation changes with no outside trigger.  Mirror:  PMC

1. 48a.

   Section Results:  “We estimated a lower bound of the epimutation rate with the linear regression results, which revealed 4.46 × 10−4 methylation polymorphisms per CG site per generation”.  “This finding contrasts with the previously reported spontaneous genetic mutation rate of 7 × 10−9 base substitutions per site per generation for these same MA lines (18).” ↩ ↩

van der Graaf, Adriaan et al.  “Rate, spectrum, and evolutionary dynamics of spontaneous epimutations.”  Proceedings of the National Academy of Sciences 112(21):6676–6681.  2015.  A statistical model fitted to methylation in Arabidopsis lines grown for up to 30 generations, estimating separately how often methylation is gained and lost at each site.  Mirror:  PMC

1. 49a.

   Section Results:  “Model-based estimates for the forward and backward CG epimutation rates (CG-all) were 2.56⋅10−4 and 6.30⋅10−4, respectively”.  “methylation loss at CG dinucleotides is globally three times as likely as methylation gain”.  “largely the result of the transgenerational accumulation of selectively neutral epimutations”. ↩ ↩

Scale only, from the published rates.  A methylated CG site lost at 6.30 × 10⁻⁴ per generation⁴⁹ lasts on average 1 ÷ 0.00063 ≈ 1,600 generations before it is lost;  an unmethylated site gains methylation after about 1 ÷ 0.000256 ≈ 3,900 generations.  Arabidopsis grows about one generation a year.  Schmitz's per-site rate of 4.46 × 10⁻⁴ against the DNA rate of 7 × 10⁻⁹⁴⁸ is a ratio of about 64,000.  Becker and colleagues found larger blocks of methylation much more stable than single sites, so a block may last far longer than one site⁷⁸. ↩

Cubas, Pilar et al.  “An epigenetic mutation responsible for natural variation in floral symmetry.”  Nature 401(6749):157–161.  1999.  A study from the John Innes Centre of the peloric toadflax, a natural variant with radially symmetric flowers, which traced it to a silenced flower-shape gene with no change in its DNA sequence.

1. 51a.

   Page 157, section Abstract:  “originally described more than 250 years ago by Linnaeus”.  “This modification is heritable and co-segregates with the mutant phenotype. Occasionally the mutant reverts phenotypically during somatic development, correlating with demethylation of Lcyc and restoration of gene expression.” ↩

Klosin, Adam et al.  “Transgenerational transmission of environmental information in C. elegans.”  Science 356(6335):320–323.  2017.  Roundworm experiments in which a rise in temperature changed the activity of a repeated transgene, and the change was passed down for at least 14 generations.

1. 52a.

   Page 320, section Abstract:  “Here, we report the observation that a temperature-induced change in expression from a Caenorhabditis elegans heterochromatic gene array can endure for at least 14 generations. Inheritance is primarily in cis with the locus, occurs through both oocytes and sperm”. ↩

Devanapally, Sindhuja et al.  “Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing.”  Proceedings of the National Academy of Sciences 112(7):2133–2138.  2015.  Experiments in roundworms in which RNA made in nerve cells silenced a matching gene in the germline, after which the silencing was followed for up to 30 generations.  The target was a transgene, and the effect varied between lines.  Mirror:  PMC

1. 53a.

   Page 2133, section Abstract:  “Inherited silencing can persist for >25 generations in the absence of the ancestral source of neuronal dsRNA.” ↩

Anway, Matthew D. et al.  “Epigenetic transgenerational actions of endocrine disruptors and male fertility.”  Science 308(5727):1466–1469.  2005.  The rat study from Michael Skinner's laboratory that started the modern claim of mammalian transgenerational inheritance:  a fungicide given in pregnancy, male fertility scored to the fourth generation.

1. 54a.

   Page 1466, section Abstract:  “These effects were transferred through the male germ line to nearly all males of all subsequent generations examined (that is, F1 to F4).” ↩

Schneider, Steffen et al.  “Vinclozolin—no transgenerational inheritance of anti-androgenic effects after maternal exposure during organogenesis via the intraperitoneal route.”  Reproductive Toxicology 37:6–14.  2013.  A repeat of the Skinner exposure by toxicologists at the chemical company BASF, using the same injection route but outbred Wistar rats, with offspring followed to the fourth generation.

1. 55a.

   Section Abstract:  “transgenerational inheritance of Vinclozolin's anti-androgenic effects was not evident in outbred Wistar rats.” ↩

Dias, Brian G., and Kerry J. Ressler.  “Parental olfactory experience influences behavior and neural structure in subsequent generations.”  Nature Neuroscience 17(1):89–96.  2014.  Mouse experiments at Emory University in which males conditioned to fear one smell had offspring, and offspring's offspring, more startled by that smell, with matching changes in the nose's wiring.  Small groups, and the grandchild results rest on single tests.  Mirror:  PMC

1. 56a.

   Section Abstract:  “subsequently conceived F1 and F2 generations had an increased behavioral sensitivity to the F0-conditioned odor, but not to other odors”.  Section Figure 4 legend:  “F2-Prop-C57, n = 8; F2-Ace-C57, n = 12”. ↩

Horsthemke, Bernhard.  “A critical view on transgenerational epigenetic inheritance in humans.”  Nature Communications 9:2973.  2018.  A review by a German human geneticist of the claimed human and mouse cases, with a list of the controls a convincing study would need.  Mirror:  PMC

1. 57a.

   Section Transgenerational inheritance in the light of evolution:  “Almost all of the experimental mouse models and the few observations in humans concern deleterious traits (congenital malformations, anxiety, glucose intolerance, obesity, cardiovascular diseases, cancer and premature death); an exception appears to be hepatic wound healing”. ↩

Sanders III, Harry F.  “Can learned behaviors be inherited?”  Answers in Genesis.  Aug 17, 2019.  A young-earth commentary on studies of inherited learned behaviour, which treats epigenetics as a designed short-term aid to adaptation.

1. 58a.

   “Epigenetic changes we know of last only a few generations if the stressors are removed.”  “epigenetics serves as an adaptive aid to organisms, but not as a mechanism of evolutionary change”. ↩

Guliuzza, Randy J.  “Engineered adaptability:  continuous environmental tracking wrap-up.”  Acts & Facts 48(8):17–19.  2019.  A popular summary, in the Institute for Creation Research's magazine, of Guliuzza's model of built-in adaptation.

1. 59a.

   Section Paragraph beginning "Three unique mechanisms":  “Epigenetics allows a population to “flex” when handling sudden stresses. The early generations rapidly express suitable traits, but then a future generation typically returns to the “baseline” after the stress passes.” ↩

Houri-Ze'evi, Leah et al.  “A tunable mechanism determines the duration of the transgenerational small RNA inheritance in C. elegans.”  Cell 165(1):88–99.  2016.  Roundworm experiments from Oded Rechavi's laboratory showing that how long inherited small-RNA silencing lasts is set by the worm's own feedback loop.

1. 60a.

   Section Abstract:  “exposure to dsRNA activates a feedback loop whereby gene-specific RNAi responses dictate the transgenerational duration of RNAi responses mounted against unrelated genes”.  The abstract gives no number of generations. ↩

Collins, Francis S.  The Language of God: A Scientist Presents Evidence for Belief.  Free Press, New York.  2006.  A book by the geneticist who led the Human Genome Project, arguing for belief in God and for evolution.  Its first chapter makes the moral law, and selfless altruism in particular, its first sign of God.

1. 61a.

   Page 27:  “Agape, or selfless altruism, presents a major challenge for the evolutionist. It is quite frankly a scandal to reductionist reasoning. It cannot be accounted for by the drive of individual selfish genes to perpetuate themselves.” ↩

2. 61b.

   Page 28:  “Another argument is that there are indirect reciprocal benefits from altruism that have provided advantages to the practitioner over evolutionary time; but this explanation cannot account for human motivation to practice small acts of conscience that no one else knows about.”  “But this kind of "ant altruism" is readily explained in evolutionary terms by the fact that the genes motivating the sterile worker ants are exactly the same ones that will be passed on by their mother to the siblings they are helping to create.” ↩

Lyons, Eric.  “Altruistic animals:  compatible with evolution?”  Apologetics Press.  Jun 17, 2007.  A short Christian apologetics article arguing that animal altruism refutes evolution.  It discusses kin selection and game theory but not reciprocity.

1. 62a.

   “Altruism is real, and even in the light of kin selection theory, remains biologically inexplicable.” ↩

Hamilton, W. D.  “The genetical evolution of social behaviour. I.”  Journal of Theoretical Biology 7(1):1–16.  1964.  The founding mathematical model of kin selection, which defines inclusive fitness and derives when a gene for helping relatives at a cost to oneself can spread.

1. 63a.

   Page 16:  “This means that for a hereditary tendency to perform an action of this kind to evolve the benefit to a sib must average at least twice the loss to the individual, the benefit to a half-sib must be at least four times the loss, to a cousin eight times and so on.”  “we expect to find that no one is prepared to sacrifice his life for any single person but that everyone will sacrifice it when he can thereby save more than two brothers, or four half-brothers, or eight first cousins.” ↩

Trivers, Robert L.  “The evolution of reciprocal altruism.”  Quarterly Review of Biology 46(1):35–57.  1971.  The model of how help between unrelated animals can be selected when partners meet repeatedly and cheats are punished, with cleaner fish, bird alarm calls and human behaviour as cases.

1. 64a.

   Page 35, section Abstract:  “A model is presented to account for the natural selection of what is termed reciprocally altruistic behavior. The model shows how selection can operate against the cheater (non-reciprocator) in the system.” ↩

Axelrod, Robert, and William D. Hamilton.  “The evolution of cooperation.”  Science 211(4489):1390–1396.  1981.  A political scientist and Hamilton report computer tournaments of the repeated prisoner's dilemma, in which the simple strategy tit-for-tat won, and show how cooperation can start and persist among non-relatives.

1. 65a.

   Page 1390:  “To account for the manifest existence of cooperation and related group behavior, such as altruism and restraint in competition, evolutionary theory has recently acquired two kinds of extension. These extensions are, broadly, genetical kinship theory (3) and reciprocation theory (4, 5).” ↩

Bourke, Andrew F. G.  “Hamilton's rule and the causes of social evolution.”  Philosophical Transactions of the Royal Society B 369(1642):20130362.  2014.  A review that gathered the field studies measuring relatedness, benefit and cost together, to see whether Hamilton's rule holds in wild animals.  Twelve studies qualified.  Mirror:  PMC

1. 66a.

   Section 2(b):  “Overall, therefore, among 10 cases of demonstrated altruism, Hamilton's rule was quantitatively fulfilled in five cases and fulfilled in some contexts in a further three cases.”  “In the single remaining case, involving worker behaviour in a halictid bee (no. 4), Hamilton's rule was not fulfilled”. ↩

Gorrell, Jamieson C. et al.  “Adopting kin enhances inclusive fitness in asocial red squirrels.”  Nature Communications 1:22.  2010.  A 19-year field study of a wild Yukon red squirrel population, with genetic relatedness, that measured the cost and benefit of the rare adoptions of orphans.  A small sample:  five adoptions.

1. 67a.

   Page 1, section Abstract:  “Adoptions were always between kin, while orphans without nearby kin were never adopted.” ↩

Hughes, William O. H. et al.  “Ancestral monogamy shows kin selection is key to the evolution of eusociality.”  Science 320(5880):1213–1216.  2008.  A comparison of queens' mating numbers across 267 species of social bees, wasps and ants, mapped on their family tree, to test whether close kinship came before or after social life.

1. 68a.

   Page 1213, section Abstract:  “We found that mating with a single male, which maximizes relatedness, is ancestral for all eight independent eusocial lineages that we investigated.” ↩

Nowak, Martin A. et al.  “The evolution of eusociality.”  Nature 466(7310):1057–1062.  2010.  A mathematical biologist, a theorist and the ant biologist E. O. Wilson argue that inclusive fitness theory is unnecessary and limited, and offer a model in which social insects arise from defended nests and pre-adapted traits.  Mirror:  PMC

1. 69a.

   Section Foundational weakness of inclusive fitness theory:  “Inclusive fitness theory is a particular mathematical approach that has many limitations. It is not a general theory of evolution.”  “relatedness is better explained as the consequence rather than the cause of eusociality”. ↩

Abbot, Patrick et al.  “Inclusive fitness theory and eusociality.”  Nature 471(7339):E1–E4.  2011.  A reply to Nowak, Tarnita and Wilson signed by 137 evolutionary biologists, defending inclusive fitness theory's mathematics and its empirical record, with sex-ratio studies as the main example.  Mirror:  PMC

1. 70a.

   “However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature.”  “Inclusive fitness theory has explained up to 96% of the sex ratio variance in across-species studies and 66% in within-species studies”. ↩

Nowak, Martin A. et al.  “Nowak et al. reply.”  Nature 471(7339):E9–E10.  2011.  The authors' answer to the five comments on their 2010 paper.

1. 71a.

   Section First paragraph:  “offer the usual defence of inclusive fitness theory, but do not take into account our new results.” ↩

Dawkins, Richard.  “The descent of Edward Wilson.”  Prospect.  May 24, 2012.  A hostile review of E. O. Wilson's The Social Conquest of Earth, defending kin selection against Wilson's turn to group selection.

1. 72a.

   “Yes it did and does work, and no it hasn’t collapsed.”  Dawkins answering Wilson's claim that kin selection "never worked well anyway, and now it has collapsed." ↩

Center for Academic Research and Training in Anthropogeny (CARTA), University of California San Diego.  Does evolutionary theory need a rethink?  Oct 9, 2014.  A web reprint of the standfirsts of Nature's paired 2014 Comment pieces, Laland and colleagues for a rethink and Wray and colleagues against.  The full Nature texts are cited through their authors' longer papers below.

1. 73a.

   “Yes, urgently. Without an extended evolutionary framework, the theory neglects key processes, say Kevin Laland and colleagues.”  “NO, ALL IS WELL”. ↩ ↩

Futuyma, Douglas J.  “Evolutionary biology today and the call for an extended synthesis.”  Interface Focus 7(5):20160145.  2017.  The reply paper at the 2016 meeting, by the author of the leading evolution textbook and one of the seven authors of the 2014 "No, all is well" piece.  It answers the extended synthesis's assumptions one by one.  Mirror:  PMC

1. 74a.

   Section Abstract:  “Evolutionary theory has been extended almost continually since the evolutionary synthesis (ES), but except for the much greater importance afforded genetic drift, the principal tenets of the ES have been strongly supported.”  “Adaptations are attributable to the sorting of genetic variation by natural selection, which remains the only known cause of increase in fitness.”  Section 4:  “There is little or no evidence that saltations occur in evolution via mutations in gene regulation.”  Section 5:  “If advocates of an EES are to convince many biologists, they will need to provide empirical support.” ↩

Bateson, Patrick et al.  “New trends in evolutionary biology: biological, philosophical and social science perspectives.”  Interface Focus 7(5):20170051.  2017.  The organizers' introduction to the published papers of the 2016 meeting.  One organizer, Laland, also leads the extended-synthesis papers.  Mirror:  PMC

1. 75a.

   Section 1:  “held at Carlton House Terrace on 7–9 November 2016.”  “nearly 300”.  “In practice, there was a great deal of discussion about standard neo-Darwinian processes, but much of the discussion also centred around whether additional processes are also causally relevant and on the different manner in which these developments are handled in different fields.” ↩

Discovery Institute.  “"Haunted" by intelligent design, an organizer reports on the Royal Society meeting.”  Evolution News.  May 26, 2017.  An unsigned Discovery Institute reply to Kevin Laland's report on the 2016 meeting in Trends in Ecology and Evolution.  Its writers attended the meeting but did not speak.

1. 76a.

   “To the chagrin of creationists and some journalists hoping for a fight, no calls for revolution were heard.”  “There are serious, fundamental flaws in neo-Darwinism.”  The first quotation is Laland's, as quoted by Discovery Institute. ↩

Wieschaus, Eric, and Christiane Nüsslein-Volhard.  “The Heidelberg screen for pattern mutants of Drosophila: a personal account.”  Annual Review of Cell and Developmental Biology 32:1–46.  2016.  The two Nobel laureates' own history of their 1979–1980 screens, with a classification of the genes they found.

1. 77a.

   Section Abstract:  “The 600 mutants we characterized could be assigned to 120 genes and represent the majority of such genes in the genome.” ↩

Becker, Claude et al.  “Spontaneous epigenetic variation in the Arabidopsis thaliana methylome.”  Nature 480(7376):245–249.  2011.  Genome-wide methylation maps of ten Arabidopsis lines descended from one plant 30 generations earlier, from Detlef Weigel's laboratory in Tübingen, separating changes at single sites from changes in whole regions.

1. 78a.

   Page 245, section Abstract:  “close to 30,000 cytosines in each strain were differentially methylated. In contrast, larger regions of contiguous methylation were much more stable, and the frequency of changes was in the same low range as that of DNA mutations.” ↩