Neuromolecular computing: a new approach to human brain evolution

Evolutionary approaches in human cognitive neurobiology traditionally emphasize macroscopic structures. It may soon be possible to supplement these studies with models of human information-processing of the molecular level. Thin-film, simulation, fluorescence microscopy, and high-resolution X-ray crystallographic studies provide evidence for transiently organized neural membrane molecular systems with possible computational properties. This review article examines evidence for hydrophobic-mismatch molecular interactions within phospholipid microdomains of a neural membrane bilayer. It is proposed that these interactions are a massively parallel algorithm which can rapidly compute near-optimal solutions to complex cognitive and physiological problems. Coupling of microdomain activity to permenant ion movements at ligand-gated and voltage-gated channels permits the conversion of molecular computations into neuron frequency codes. Evidence for microdomain transport of proteins to specific locations within the bilayer suggests that neuromolecular computation may be under some genetic control and thus modifiable by natural selection. A possible experimental approach for examining evolutionary changes in neuromolecular computation is briefly discussed. Received: 2 October 1998 / Accepted in revised form: 19 March 1999     

Survival of the fattest: body stores on migration and survival in red knots Calidris canutus islandica

Severe summer weather in Greenland and Arctic Canada in 1972 and 1974 caused very poor breeding success and elevated adult mortality in red knots Calidris canutus islandica. We show that those individual knots that are known to have survived these summers were in better than average nutritional condition shortly before departure from their late spring staging area in west Iceland. The condition index of previously banded or subsequently recovered birds captured in Iceland was positively related to the number of summers they were known to have survived. Body stores carried from the last spring staging area to the breeding grounds appear to offer Arctic-breeding shorebirds significant selective advantages: they are used for physical transformation from migration to breeding condition, and in years when weather is difficult may enable survival after arrival on the breeding grounds.     

Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion

Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.     

Designing babies: morally permissible ways to modify the human genome

My focus in this paper is the question of the moral acceptability of attempts to modify the human genome. Much of the debate in this area has revolved around the distinction between supposedly therapeutic modification on the one hand, and eugenic modification on the other. In the first part of the paper I reject some recent arguments against genetic engineering. In the second part I seek to distinguish between permissible and impermissible forms of intervention in such a way that does not appeal to the therapeutic/eugenic distinction. If I am right much of what we would intuitively call eugenic intervention will be morally acceptable. Central to my argument is an asymmetry in the way genetic engineers can influence a person's capacities on the one hand and life-goals on the other. Forms of genetic intervention that have a high probability of producing a mismatch of life-goals and capacities will be ruled out.     

Genetic basis of human brain evolution: accelerating along the primate speedway

Using novel variations of traditional methods, report in the December 29(th) issue of Cell that diverse genes involved in neural biology (particularly those critical in development) show higher rates of protein evolution in primates than in rodents-particularly in the lineage leading to humans.     

Sibling rivalry among paralogs promotes evolution of the human brain

Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution.     

Stone tools, language and the brain in human evolution

Long-standing speculations and more recent hypotheses propose a variety of possible evolutionary connections between language, gesture and tool use. These arguments have received important new support from neuroscientific research on praxis, observational action understanding and vocal language demonstrating substantial functional/anatomical overlap between these behaviours. However, valid reasons for scepticism remain as well as substantial differences in detail between alternative evolutionary hypotheses. Here, we review the current status of alternative 'gestural' and 'technological' hypotheses of language origins, drawing on current evidence of the neural bases of speech and tool use generally, and on recent studies of the neural correlates of Palaeolithic technology specifically.     

Physico-chemical determinants of physiOlogical evolution: from protocell to the human

One of the key physiological problems of evolution is elucidation of the role of environmental inorganic factors in origin of life. A statement is substantiated that a highly significant event in evolution of life was the appearance of protocells with the K cytoplasm in K water reservoirs with their subsequent adaptation to the environment in which Na dominated. This step was accompanied by replacement of the cell envelope with the cell plasma membrane. Precursors of animals' elaborated mechanism of maintenance of the K-cytoplasm with Na-counterkation in the environment. In plants, Na remains a trace element, in animals the Na and K contents are approximately equal, but they are present in different fluid phases. In animals presence of Na+ in the external medium, K+ inside cells has become an initial pre-requisition for electrogenesis and appearance of asymmetrical cells. Electrogenesis of these cells has become a physiological pre-requisition for cell differentiation, the appearance of the nerve cell. Asymmetrical cell has provided development of absorption, digestion, excretion, respiration. Formation of the inner medium has become a prerequisite for establishment of homeostasis. Serum osmolality, sodium concentration, pH, Ca2+ are the most rigidly maintained constants in the blood serum of humans.     

Isolation of a large aggregating proteoglycan from human brain.

A large proteoglycan (365 kDa), identified with monoclonal antibodies raised against chondroitin sulfate, was isolated from human brain. The isolation required anion-exchange chromatography followed by gel filtration through a Sephacryl S-500 column. The proteoglycan bound specifically to [3H]hyaluronate (HA). The binding was not reduced by high salt concentrations (up to 4 M) and was inhibited at low pH (< 4.0). The binding was inhibited by the octamer and decamer (but not the hexamer) oligosaccharides of HA. Limited proteolysis of the proteoglycan gave rise to a relatively stable polypeptide (80 kDa). The amino-terminal sequence of the 80-kDa polypeptide was identical to the cDNA-derived amino-terminal sequence of versican, a large human fibroblast proteoglycan. A monoclonal antibody raised against bovine proteoglycans and recognizing the versican core protein reacted by immunoblotting with the proteoglycan isolated from human brain. The antibody was used to localize the proteoglycan in acetone-fixed cryostat sections of bovine spinal cord. The localization of the proteoglycan in the central nervous system was identical to that previously reported for glial hyaluronate-binding protein (GHAP), a 60-kDa glycoprotein of the brain extracellular matrix (ECM). However, a major difference was observed with respect to the sensitivity of the two antigens to hyaluronidase. As previously reported, GHAP was released from the tissue by hyaluronidase digestion, whereas the proteoglycan persisted under these conditions. We conclude that the protein-hyaluronate aggregates in brain ECM contain both GHAP and versican, that GHAP is only retained in the ECM by its interaction with hyaluronate, and that the proteoglycan is anchored in some other manner and probably connects cell surfaces with the ECM since it was not released by hyaluronidase digestion.