No abstract

No abstract

Galectins are proteins that regulate immune responses through the recognition of cell-surface glycans. We present evidence that 16 human galectin genes are expressed at the maternal-fetal interface and demonstrate that a cluster of 5 galectin genes on human chromosome 19 emerged during primate evolution as a result of duplication and rearrangement of genes and pseudogenes via a birth and death process primarily mediated by transposable long interspersed nuclear elements (LINEs). Genes in the cluster are found only in anthropoids, a group of primate species that differ from their strepsirrhine counterparts by having relatively large brains and long gestations. Three of the human cluster genes (LGALS13, -14, and -16) were found to be placenta-specific. Homology modeling revealed conserved three-dimensional structures of galectins in the human cluster; however, analyses of 24 newly derived and 69 publicly available sequences in 10 anthropoid species indicate functional diversification by evidence of positive selection and amino acid replacements in carbohydrate-recognition domains. Moreover, we demonstrate altered sugar-binding capacities of 6 recombinant galectins in the cluster. We show that human placenta-specific galectins are predominantly expressed by the syncytiotrophoblast, a primary site of metabolic exchange where, early during pregnancy, the fetus comes in contact with immune cells circulating in maternal blood. Because ex vivo functional assays demonstrate that placenta-specific galectins induce the apoptosis of T lymphocytes, we propose that these galectins reduce the danger of maternal immune attacks on the fetal semiallograft, presumably conferring additional immune tolerance mechanisms and in turn sustaining hemochorial placentation during the long gestation of anthropoid primates. adaptive evolution ͉ glycocode ͉ maternal-fetal immune tolerance ͉ PP13 ͉ preeclampsia

The placenta is essential for the success of therian mammalian reproduction. Intense selective pressure has shaped changes in placental anatomy and function during mammalian cladogenesis. Here we challenge the view that the hemochorial placenta is a derived feature in haplorhine primates. Using phylogenetic and statistical analyses of molecular and morphological data, we demonstrate that the ancestral eutherian mammalian placenta had the distinctive features of (i) hemochorial placental interface, (ii) a discoid shape, and (iii) a labyrinthine maternofetal interdigitation. These results reveal that the first eutherians had a deeply invasive placenta and imply that the major role of the placenta in sustaining pregnancy and promoting gestational development existed throughout the eutherian lineage that descended to humans from the last common ancestor of placental mammals. The ancestral state reconstructions demonstrate both clade-specific patterns of placentation and specific cases of convergent evolution within individual eutherian clades. Determining the mammalian pattern of change in placental morphology is important for understanding the evolutionary pressures faced by these lineages. The effects of selection pressures on the efficiency of placentation may stem from changes in nutritional demand, gestational length, number of embryos per pregnancy, uterine shape, and maternal body constitution. The influence of these factors on placental development needs further investigation. discoid shape ͉ Eutheria ͉ hemochorial ͉ maternofetal interdigitation ͉ villous type

No abstract

Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II͞III of dorsolateral prefrontal cortex (area 9L). However, the human glia-neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia-neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as ''theory of mind'' (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain.allometry ͉ human evolution ͉ prefrontal cortex ͉ brain energy metabolism ͉ language evolution H umans are distinguished from other primates by a dramatically enlarged neocortex and the elaboration of cognitive capacities that have culminated in the evolution of language, technological innovation, and complex social behavior. Expansion of the human brain entails high metabolic costs (1). Although the human brain comprises only Ϸ2% of body mass, it captures Ϸ20% of the body's total glucose utilization (2). At the same time, because the metabolic rate per gram of neural tissue generally decreases with larger brain size, the human brain is more energetically efficient than that in smaller-brained primate species (3). Despite this evidence for relatively lower mass-specific brain metabolism in humans, recent microarray studies have shown that genes involved in neuronal signaling and energy production are up-regulated in the human neocortex compared with chimpanzees and other great apes (4, 5). Furthermore, evidence for positive selection in the human lineage for genes that encode components of the mitochondrial electrontransport chain suggests that there has been evolutionary pressure for high rates of aerobic energy consumption in metabolically active cells, such as neurons (6). Taken collectively, these findings suggest that neuronal activity level and energy expenditure per neuron have become enhanced in human evolution, even as mass-specific rates of brain metabolism declined. This pattern is consistent with a model that predicts that, with increases in brain size, a progressively smaller fraction of the total neuron population may be concurrently active, lea...

The relationships among 153 EF-hand (calcium-modulated) proteins of known amino acid sequence were determined using the method of maximum parsimony. These proteins can be ordered into 12 distinct subfamilies--calmodulin, troponin C, essential light chain of myosin, regulatory light chain, sarcoplasmic calcium binding protein, calpain, aequorin, Stronglyocentrotus purpuratus ectodermal protein, calbindin 28 kd, parvalbumin, alpha-actinin, and S100/intestinal calcium-binding protein. Eight individual proteins--calcineurin B from Bos, troponin C from Astacus, calcium vector protein from Branchiostoma, caltractin from Chlamydomonas, cell-division-cycle 31 gene product from Saccharomyces, 10-kd calcium-binding protein from Tetrahymena, LPS1 eight-domain protein from Lytechinus, and calcium-binding protein from Streptomyces--are tentatively identified as unique; that is, each may be the sole representative of another subfamily. We present dendrograms showing the relationships among the subfamilies and uniques as well as dendrograms showing relationships within each subfamily. The EF-hand proteins have been characterized from a broad range of organismal sources, and they have an enormous range of function. This is reflected in the complexity of the dendrograms. At this time we urge caution in assigning a simple scheme of gene duplications to account for the evolution of the 600 EF-hand domains of known sequence.

Gene expression profiles from the anterior cingulate cortex (ACC) of human, chimpanzee, gorilla, and macaque samples provide clues about genetic regulatory changes in human and other catarrhine primate brains. The ACC, a cerebral neocortical region, has humanspecific histological features. Physiologically, an individual's ACC displays increased activity during that individual's performance of cognitive tasks. Of Ϸ45,000 probe sets on microarray chips representing transcripts of all or most human genes, Ϸ16,000 were commonly detected in human ACC samples and comparable numbers, 14,000 -15,000, in gorilla and chimpanzee ACC samples. Phylogenetic results obtained from gene expression profiles contradict the traditional expectation that the non-human African apes (i.e., chimpanzee and gorilla) should be more like each other than either should be like humans. Instead, the chimpanzee ACC profiles are more like the human than like the gorilla; these profiles demonstrate that chimpanzees are the sister group of humans. Moreover, for those unambiguous expression changes mapping to important biological processes and molecular functions that statistically are significantly represented in the data, the chimpanzee clade shows at least as much apparent regulatory evolution as does the human clade. Among important changes in the ancestry of both humans and chimpanzees, but to a greater extent in humans, are the up-regulated expression profiles of aerobic energy metabolism genes and neuronal functionrelated genes, suggesting that increased neuronal activity required increased supplies of energy. T raditionally, humans are presumed to have superior cognitive abilities and, thereby, to be very different from other animals. This presumed superiority lies in the supposed uniqueness of such human abilities as producing cultural artifacts and engaging in language and symbolic thought. Recent work, however, shows that chimpanzees, who are the sister group of humans (1-6), engage in culture (7), use tools (8-10), and display rudimentary forms of language (11-13). Moreover, with regard to DNA changes that alter proteins and are favored by natural selection, chimpanzees diverge about as much from the most recent common human-chimpanzee ancestor as do humans (1,14). Here, by estimating the relative abundance of transcribed messages of different expressed genes, we examine in humans and several other catarrhine primates gene expression profiles in an important cerebral region involved in cognition, the anterior cingulate cortex (ACC).The ACC is typically viewed as a bridge between paleocortex and neocortex but is actually part of the neocortex (15). Histologically, the ACC shows human-specific features. For example, clusters of spindle cell pyramidal neurons occur in the ACC of humans, lesser numbers in bonobo and common chimpanzees, lesser yet in gorillas, least in orangutans, and not at all in other primates and other mammals. Moreover, the spindle cells in humans are more than twice as large as in common and bonobo chimpanzees and three...