Neo-Darwinian theory about evolution

chimp photo

You will see from the posts below that there is only a 1-2% difference in DNA sequence between human and chimpanzee and 80% of the proteins of human and chimpanzee are different. The burning question is what are the differences (if any) between the genes expressed in embryogenesis, because these are the genes most likely responsible for the radical phenotype differences between human and chimp. The next step for me is to go to the gene databases and compare the genes below in human and chimp. These genes are all different from the 10 genes listed in the post below this one.

1. Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis - We show that fibroblast growth factor 2 (FGF2) and FGF receptors are transiently expressed by cells of the pseudostratified ventricular epithelium (PVE) during early neurogenesis. A single microinjection of FGF2 into cerebral ventricles of rat embryos at E15.5 increased the volume and total number of neurons in the adult cerebral cortex by 18% and 87%, respectively. Microinjection of FGF2 by the end of neurogenesis, at E20.5, selectively increased the number of glia. Mice lacking the FGF2 gene had fewer cortical neurons and glia at maturity. BrdU studies in FGF2-microinjected and FGF2-null animals suggested that FGF2 increases the proportion of dividing cells in the PVE without affecting the cell-cycle length. Thus, FGF2 increases the number of rounds of division of cortical progenitors.

2. Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. - Neocortical neuroblast cell lines were used to clone G-protein-coupled receptor (GPCR) genes to study signaling mechanisms regulating cortical neurogenesis. One putative GPCR gene displayed an in situ expression pattern enriched in cortical neurogenic regions and was therefore named ventricular zone gene-1 (vzg-1). These analyses identify the vzg-1 gene product as a receptor for LPA, suggesting the operation of LPA signaling mechanisms in cortical neurogenesis. Vzg-1 therefore provides a link between extracellular LPA and the activation of LPA-mediated signaling pathways through a single receptor and will allow new investigations into LPA signaling both in neural and nonneural systems.

3. An RNA gene expressed during cortical development evolved rapidly in humans - The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these ‘human accelerated regions’, HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal–Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal–Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other human accelerated regions provide new candidates in the search for uniquely human biology.

4. Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development In Vivo - Within the vertebrate nervous system, the presence of many different lineages of neurons and glia complicates the molecular characterization of single neuronal populations. In order to elucidate molecular mechanisms underlying the specification and development of corticospinal motor neurons (CSMN)..  Loss-of-function experiments in null mutant mice for Ctip2 (also known as Bcl11b), one of the newly characterized genes, demonstrate that it plays a critical role in the development of CSMN axonal projections to the spinal cord in vivo, confirming that we identified central genetic determinants of the CSMN population.

5. Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis - Our understanding of the evolution, formation, and pathological disruption of human brain circuits is impeded by a lack of comprehensive data on the developing brain transcriptome. A whole-genome, exon-level expression analysis of 13 regions from left and right sides of the mid-fetal human brain revealed that 76% of genes are expressed, and 44% of these are differentially regulated. Of particular relevance to cognitive specializations, we have characterized the transcriptional landscapes of prefrontal cortex and perisylvian speech and language areas, which exhibit a population-level global expression symmetry. We show that differentially expressed genes are more frequently associated with human-specific evolution of putative cis-regulatory elements. These data provide a wealth of biological insights into the complex transcriptional and molecular underpinnings of human brain development and evolution.

6. Genomic imprinting and the differential roles of parental genomes in brain development - Certain genes are expressed either from the maternal or the paternal genome as a result of genomic imprinting, a process that confers functional differences on parental genomes during mammalian development. In this study we focus on the cumulative effects of imprinted genes on brain development by examining the fate of androgenetic (Ag: duplicated paternal genome) and parthenogenetic/gynogenetic (Pg/Gg: duplicated maternal genome) cells in chimeric embryos. Striking cell autonomous differences in the phenotypic properties of the uniparental cells were observed. Ag cells contributed substantially to the hypothalamic structures and not the cortex. By contrast, Pg/Gg cells contributed substantially to the cortex, striatum and hippocampus but not to the hypothalamic structures. Furthermore growth of the brain was enhanced by Pg/Gg and retarded by Ag cells. We propose that genomic imprinting may be responsible for a change in strategy controlling brain development in mammals. In particular, genomic imprinting may have facilitated a rapid non-linear expansion of the brain, especially the cortex, during development over evolutionary time.

7. Cell-cycle control and cortical development - The spatio-temporal timing of the last round of mitosis, followed by the migration of neuroblasts to the cortical plate leads to the formation of the six-layered cortex that is subdivided into functionally defined cortical areas. Whereas many of the cellular and molecular mechanisms have been established in rodents, there are a number of unique features that require further elucidation in primates. Recent findings both in rodents and in primates indicate that regulation of the cell cycle, specifically of the G1 phase has a crucial role in controlling area-specific rates of neuron production and the generation of cytoarchitectonic maps… Embryonic thalamocortical projections are likely to influence areal specification during early stages of corticogenesis by modulating proliferation.

8. Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex - Because noggin can induce Fgf8 expression, we examined noggin and BMP signaling in the Emx2 mutant. As the telencephalic vesicle closed, Nog expression was expanded and BMP activity reduced, potentially leading to FGF8 upregulation. Our findings point to a cross-regulation of BMP, FGF, and WNT signaling in the early telencephalon, integrated by EMX2, and required for normal cortical development. When endogenous BMP signaling is inhibited by noggin, robust Fgf8 expression appears ectopically in the cortical primordium.

9. Regional and Cellular Patterns of reelin mRNA Expression in the Forebrain of the Developing and Adult Mouse - The reelin gene encodes an extracellular protein that is crucial for neuronal migration in laminated brain regions. During embryogenesis,reelin was detected in the cerebral cortex in Cajal-Retzius cells but not in the GABAergic neurons of layer I. At prenatal stages, reelin was also expressed in the olfactory bulb, and striatum and in restricted nuclei in the ventral telencephalon, hypothalamus, thalamus, and pretectum. At postnatal stages, reelin transcripts gradually disappeared from Cajal-Retzius cells, at the same time as they appeared in subsets of GABAergic neurons distributed throughout neocortical and hippocampal layers. In other telencephalic and diencephalic regions,reelin expression decreased steadily during the postnatal period.

10. Independent Expression of the α and β c-erbA Genes in Developing Rat Brain - Thyroid hormone is important for normal brain development. Cellular responses to thyroid hormone are mediated by multiple nuclear receptors, classified into α- and β-subtypes. In the rat, expression of both the α and β genes results in several translation products.  The differential temporal and spatial distribution as well as coexpression at comparable levels in certain brain regions suggest different roles for the c-erbA proteins during brain development and in the mature animal.

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You will see from my first post below that there is only a 1-2% difference in DNA sequence between human and chimpanzee. This post will perhaps only be meaningful to experts. These are research papers that describe specific genes that are expressed in the midbrain during development. The title to the paper appears in bold type. The next step for me is to go to the gene databases and to find the DNA sequence differences (if any) between these genes in the human and chimpanzee.

1. Differential Display of Genes Expressed at the Midbrain – Hindbrain Junction Identifies sprouty2: An FGF8-Inducible Member of a Family of Intracellular FGF Antagonists - A clone upregulated in cDNA derived from rhombomere 1 tissue showed a 91% identity at the nucleotide level to the putative human receptor tyrosine kinase antagonist: sprouty2. In situ hybridization on whole chick embryos showed chick sprouty2 to be expressed initially within the isthmus and rhombomere 1, spatially and temporally coincident with Fgf8 expression. However, at later stages this domain was more extensive than that of Fgf8. Introduction of ligand-coated beads into either midbrain or hindbrain region revealed that sprouty2 could be rapidly induced by FGF8. These data suggest that sprouty2 participates in a negative feedback regulatory loop to modulate the patterning activity of FGF8 at the isthmus

2. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function - Targeted gene disruption in the mouse shows that the Sonic hedgehog(Shh) gene plays a critical role in patterning of vertebrate embryonic tissues, including the brain and spinal cord, the axial skeleton and the limbs.

3. Pax-5 is expressed at the midbrain-hindbrain boundary during mouse development - Pax-5 was expressed in the developing brain, predominantly at the midbrain-hindbrain boundary, and in the neural tube. While the neural tube expression pattern overlapped completely with Pax-2 and Pax-8, the expression pattern in the brain was only partially overlapping. Unlike Pax-2 and Pax-8, Pax-5 was not expressed in the developing excretory system, thyroid, eye or ear. Our data suggest that Pax-5 has a role in the development of the central nervous system.

4. The midbrain-hindbrain phenotype of Wnt-1 (minus) mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum - By examining embryonic expression of the mouse engrailed (En) genes, from 8.0 to 9.5 days postcoitum, we demonstrate that Wnt-1 primarily regulates midbrain development. The midbrain itself is required for normal development of the metencephalon. Wnt-1 and a related gene, Wnt-3a, are coexpressed from early somite stages in dorsal aspects of the myelencephalon and spinal cord. We suggest that functional redundancy between these two genes accounts for the lack of a caudal central nervous system phenotype.

5. Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner - The role of transcription factors in regulating the development of midbrain dopaminergic (mDA) neurons is intensively studied owing to the involvement of these neurons in diverse neurological disorders. Here we demonstrate novel roles for the forkhead/winged helix transcription factors Foxa1 and Foxa2 in the specification and differentiation of mDA neurons by analysing the phenotype of Foxa1 and Foxa2 single- and double-mutant mouse embryos. During specification, Foxa1 and Foxa2 regulate the extent of neurogenesis in mDA progenitors by positively regulating Ngn2 (Neurog2) expression. Subsequently, Foxa1 and Foxa2 regulate the expression of Nurr1 (Nr4a2) and engrailed 1 in immature neurons and the expression of aromatic l-amino acid decarboxylase and tyrosine hydroxylase in mature neurons during early and late differentiation of midbrain dopaminergic neurons. Interestingly, genetic evidence indicates that these functions require different gene dosages of Foxa1 and Foxa2.

6. A MicroRNA Feedback Circuit in Midbrain Dopamine Neurons - MicroRNAs (miRNAs) are evolutionarily conserved, 18- to 25-nucleotide, non–protein coding transcripts that posttranscriptionally regulate gene expression during development. miRNAs also occur in postmitotic cells, such as neurons in the mammalian central nervous system, but their function is less well characterized. We investigated the role of miRNAs in mammalian midbrain dopaminergic neurons (DNs). We identified a miRNA, miR-133b, that is specifically expressed in midbrain DNs.

7. Expression patterns of the homeo box-containing genes En-1 and En-2 and the proto-oncogene int-1 diverge during mouse development - We have compared the expression of the murine genes En-1,En-2, and in-1 during development by in situ hybridization. Expression of all three genes was first detected at 8.0 days in overlapping bands of the anterior neural folds. By 12.0 days the expression patterns diverged. En-1 and En-2 were expressed in a similar ring of cells in the central nervous system (CNS) at the midbrain/hindbrain junction.

8. Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain - Mutations in two genes affect the formation of the boundary between midbrain and hindbrain (MHB): no isthmus (noi) and acerebellar (ace). noi mutant embryos lack the MHB constriction, the cerebellum and optic tectum, as well as the pronephric duct. Analysis of noi mutant embryos with neuron-specific antibodies shows that the MHB region and the dorsal and ventral midbrain are absent or abnormal, but that the rostral hindbrain is unaffected with the exception of the cerebellum. Using markers that are expressed during its formation (eng, wnt1 and pax-b), we find that the MHB region is already misspecified in noi mutant embryos during late gastrulation.

9. The caudal limit of Otx2 gene expression as a marker of the midbrain/hindbrain boundary: a study using in situ hybridisation and chick/quail homotopic grafts - Chick/quail homotopic grafts of various portions of the midbrain/hindbrain domain have shown that the progeny of the cells located in the caudal mesencephalic vesicle at stage HH10 are found within the rhombomere 1 as early as stage HH14. Furthermore, our results indicate that the cells forming the HH20 constriction (coinciding with the caudal Otx2 limit) are the progeny of those located at the caudal Otx2 limit at stage HH10 (within the mesencephalic vesicle). As a result, the Otx2-positive portion of the HH10 mesencephalic vesicle gives rise to the HH20 mesencephalon, while the Otx2-negative portion gives rise to the HH20 rostral rhombomere 1.

10. Inactivation of the (β)-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development - ('bgr;)-Catenin is a central component of both the cadherin-catenin cell adhesion complex and the Wnt signaling pathway. We have investigated the role of (β)-catenin during brain morphogenesis, by specifically inactivating the (β)-catenin gene in the region of Wnt1 expression. To achieve this, mice with a conditional ('floxed') allele of (β)-catenin with required exons flanked by loxP recombination sequences were intercrossed with transgenic mice that expressed Cre recombinase under control of Wnt1 regulatory sequences. (β)-catenin gene deletion resulted in dramatic brain malformation and failure of craniofacial development. Absence of part of the midbrain and all of the cerebellum is reminiscent of the conventional Wnt1 knockout (Wnt1(−)(/)(−)), suggesting that Wnt1 acts through (β)-catenin in controlling midbrain-hindbrain development.


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A research paper in 2005 found that although there is only 1-2% difference in DNA sequence between humans and chimpanzees, 80% of the proteins of human and chimp are different. This was a very limited study. For starters they excluded from the study complex proteins that are synthesized from multiple genes, such as major histocompatibility complex (MHC) and immunoglobin, and mitochondrial proteins. Of the thousands of proteins in the body and brain of humans and chimp they ended up comparing just 127 proteins that have a one-on-one relation between DNA sequence and primary amino acid sequence in the protein. In other words the actual 3-D structures of the proteins were not compared which also would have a bearing on whether the proteins were different or the same. The report found that although only 25 out of the 127 proteins had identical amino acid sequences, most of the differences in the amino acid sequences were too small to explain the actual phenotype differences between human and chimp. In a lot of the proteins compared there were only a few differences in the amino acid polypeptide chains. The report suggests that phenotypic differences must be controlled by a small proportion of genes, either by regulatory genes or by major effect genes. Since 2005 the amount of data in the genetic databases would have increased exponentially and there is here an urgent need to do a follow up study in this area. This blog has been set up primarily to look into this issue in great depth. This issue holds the key to proving whether neo-Darwinism is right or wrong. We have to find these “regulatory genes or major effect genes” that are responsible for phenotype differences.

chimp photo



An article that was published in 1975, before the actual sequencing of the human and chimp genomes, entitled ‘Evolution at Two Levels in Humans and Chimpanzees’, had already made extensive enquiry into this vexed question that at the molecular level, that is to say our DNA and our proteins, the human and the chimp are even more similar than sibling species, and yet the phenotypes of the human and the chimp are so different. Sibling species are almost identical morphologically but are reproductively isolated, that is to say that cannot produce viable offspring (different sorts of fish or birds for example).

According to the article: ‘The molecular similarity between chimpanzees and humans is extraordinary because they differ far more than sibling species in anatomy and way of life. Although humans and chimpanzees are rather similar in the structure of the thorax and arms, they differ substantially not only in brain size but also in the anatomy of the pelvis, foot, and jaws, as well as in relative lengths of limbs and digits. Humans and chimpanzees also differ significantly in many other anatomical respects, to the extent that nearly every bone in the body of a chimpanzee is readily distinguishable in shape or size from its human counterpart. Associated with these anatomical differences there are, of course, major differences in posture (see cover picture), mode of locomotion, methods of procuring food, and means of communication. Because of these major differences in anatomy and way of life, biologists place the two species not just in separate genera but in separate families. So it appears that molecular and organismal methods of evaluating the chimpanzee- human difference yield quite different conclusions’.

The article concludes: ‘The contrasts between organismal and molecular evolution indicate that the two processes are to a large extent independent of one another. Is it possible, therefore, that species diversity results from molecular changes other than sequence differences in proteins? It has been suggested that major anatomical changes usually result from mutations affecting the expression of genes. According to this hypothesis, small differences in the time of activation or in the level of activity of a single gene could in principle influence considerably the systems controlling embryonic development. The organismal differences between chimpanzees and humans would then result chiefly from genetic changes in a few regulatory systems, while amino acid substitutions in general would rarely be a key factor in major adaptive shifts’.

What this means is that Neo-Darwinism (the post-Darwinian concept that species evolve by the natural selection of adaptive phenotypes caused by random mutation of genes) cannot explain how the human and chimp can be so similar in genotype and yet so dissimilar in phenotype. Are we expected to believe that over a period of six million years or so a small number of core regulatory genes created two separate and very different species with widely different phenotypes, and yet made minimal (and even negligible) mutational changes in the DNA and the proteins of these two species? Are we expected to believe that this process of species differentiation can possibly be random?

You will see in some of the articles on this website (Inner Self Located & Our Unconscious Soul) that the embryo cranium is bulging with midbrain and is firing spontaneously five weeks after conception. In my theories this is the soul or vital force. It’s my bet that the genes that are expressed in this early embryonic stage that cause the midbrain to fire, are the ‘regulatory’ genes responsible for the differentiation of the species.  

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