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The new world primates as animal models of glucocorticoid resistance.

Many New World primate species have greatly increased plasma cortisol concentrations, decreased plasma cortisol binding globulin capacity and affinity, marked resistance of the hypothalamic-pituitary-adrenal axis to suppression by dexamethasone, and no biological evidence of glucocorticoid excess. These primates also have high levels of circulating progesterone, estrogen, mineralocorticoid, androgen and vitamin D. The glucocorticoid target tissues that have been examined (circulating mononuclear lymphocytes and cultured skin fibroblasts) have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. Transformation of B-lymphocytes with the Epstein-Barr virus leads to glucocorticoid receptor induction that is less than that observed with cells from Old World primates. The receptor in these cells has a low affinity for dexamethasone. The low affinity leads to an increased loss of specific bound ligand during thermal activation. Meroreceptor generation is normal. The molecular weight of the receptor, determined by SDS-PAGE, is similar to that of Old World primates (approximately 92,000) and the activation pattern per se, examined in vitro by heating cytosol and performing phosphocellulose chromatography, appears similar to that of human controls. The ratios of nuclear to cytosolic hormone-receptor-complexes and of cytosolic activated to unactivated receptor complexes in intact cells are similar to Old World primates. Results from mixing studies do not support the hypothesis that a binding inhibitor(s) or a deficient cytosolic positive modifier(s) of binding underlies the findings in these primates. The New World primates, unlike men with the syndrome of primary cortisol resistance, have compensated for their condition with intra-adrenal and mineralocorticoid receptor adaptations. Thus, unlike Old World primates, cortisol in New World primates has only weak sodium-retaining potency because the aldosterone receptor has a low affinity for cortisol. The common element that would explain the apparent resistance to six steroid hormones in New World primates remains unknown.

Adrenal Glands

Toward a molecular paleontology of primate genomes. I. The HindIII and EcoRI dimer families of alphoid DNAs.

Families of related, but nonidentical repetitive DNA sequences, termed the alphoid DNAs, have been identified and characterized in representative species from seven major primate Families. The sequences appear as old as the primate Order itself: they are found in a prosimian (lemur), in a New World monkey, and in all Old World primates examined, including man. The alphoid DNAs are uniquely primate sequences and they may represent the most abundant repetitive DNAs in the primate genome. - A classification scheme for two major families of alphoid DNAs is proposed that is based upon restriction enzyme analysis and Southern blotting with radioactive probes prepared from component alpha DNA (Maio, 1971) and from the human EcoRI dimer sequences (Manuelidis, 1976). The family of alphoid DNAs that hybridizes readily with component alpha is termed the HindIII family of alphoid DNAs. This family shows an almost universal distribution among present-day primates. The family of DNA sequences that hybridizes readily with the human EcoRI dimer probe is termed the EcoRI dimer family of alphoid DNAs. This family may be restricted to the great apes and man. The two probes permitted the discrimination of different, but related alphoid families in present-day primates. Multiple alphoid sequence families are found within the genomes of individual primates and the major primate taxa can be characterized by the representations of the various alphoid DNAs within their genomes. - An Appendix is presented (Brown et al., 1981) indicating that competition hybridization effects may influence the autoradiographic banding patterns, and hence, the interpretations of Southern filter-transfer hybridizations when dealing with related repetitive sequences such as the alphoid DNAs that are present in abundance in eukaryotic genomes.

Animals

Baboon and cotton-top tamarin B2m cDNA sequences and the evolution of primate beta 2-microglobulin.

Nonhuman primates represent phylogenetic intermediates for studying the divergence of human and murine beta 2Ms. We report the nucleotide sequences of B2m cDNA clones from a baboon cell line, 26CB-1 (Papio hamadryas; primates: Cercopithecoidea), and a cotton-top tamarin cell line, 1605L (Saguinus oedipus; primates: Ceboidea). The baboon and tamarin B2m sequences indicate a very slow rate of B2m evolution in primates relative to that in murid rodents. Phenotypic evolution of beta 2M has also been very conservative in primates, with only 9-14 substitutions separating baboon or tamarin beta 2Ms from those of humans or orangutans. Analyses of silent and amino-acid-altering nucleotide substitutions provide evidence that negative selection has acted to limit variability in beta strands of primate beta 2Ms, while positive selection has promoted diversity in non-beta-strand regions of murine beta 2Ms. No evidence for the action of selection upon beta 2M residues that contact the class I heavy chain was found in primates or mice. The finding that different selective forces have operated upon primate and murine beta 2Ms suggests that beta 2M may have evolved to serve distinct functions in primates and mice.

Amino Acid Sequence

Toward a molecular paleontology of primate genomes. II. The KpnI families of alphoid DNAs.

KpnI restriction of anthropoid primate DNAs, from a New World monkey to man, releases a series of segments that are remarkable among all of the alphoid DNAs in the constancy of their relative amounts in the various primate genomes, in their long-range organization, and in their internal sequence structure. These segments are labeled the KpnI A, B, C and D segments. Cross-hybridization analysis by Southern filter-transfer hybridization indicates that the KpnI segments represent separate and distinct families of alphoid DNAs. These families are termed the KpnI A, B, C and D families of alphoid sequences, of which only the KpnI A and B families were studied in detail here. - Evidence is presented suggesting that the KpnI segments do not exist as long, tandemly repeated sequences in the primate genome: rather, they may occur interspersed among other, perhaps nonalphoid sequences. From the stained gel patterns and from Southern filter-transfer hybridization experiments, the KpnI families appear to be absent from the genomes of the two prosimians studied - the galago and the black lemur. The KpnI A and B families are found among all of the anthropoid primates, including the New World capuchin monkey. The KpnI C family was detected in the genomes of the Old World anthropoid primates whereas the KpnI D family was detected only among the great apes and man. - The results are in accord with the observation (Musich et al., 1980) that with the continued evolutionary development of the primate Order, there has been a parallel trend toward an increased number and variety of alphoid DNA sequences. The properties of the KpnI families suggest that these sequences, unique among the alphoid DNAs, have been conservatively maintained throughout primate phylogeny and that they are among the most ancient of all primate DNAs.

Animals

Evolution of DNA sequences has been retarded in Malagasy primates.

It is generally accepted that there are six major groups of living primates: (1) lemurs (including all the primates of Madagascar), (2) lorises (including galago and potto), (3) tarsiers, (4) New World monkeys, (5) Old World monkeys and (6) apes (including man). Tree shrews, once considered to be primates, are now generally recognized as not significantly more closely related to the six groups than other mammals. The first surviving primate lines to diverge from the common primate ancestor are believed to have given rise to one or more of the first three groups. However, the fossil record is insufficient to determine their relative branching order. Furthermore, neither morphological considerations nor studies of protein evolution produce unanimity as to whether tarsiers are more closely related to the prosimians (the lemurs plus lorises) or the simians (the monkeys and apes). In an attempt to resolve these discrepancies, we have measured the DNA sequence difference between several primates. We report here that the evolution of DNA of primates from Madagascar is significantly less than that of all other groups of living primates. This is not expected in the simplest form of the theory of neutral selection and may be important for our understanding of evolution at the molecular level.

Animals

Primate origins: plugging the gaps.

Recent discoveries of fossil primate specimens have produced several surprises and challenged prevailing views of early primate evolution. Plesiadapiformes, long regarded as 'archaic primates', may perhaps be linked to the peculiar colugos instead. Inferred relationships of the earliest known undoubted primates (adapids and omomyids) are in turmoil. Both groups have been proposed as sources for the simian primates. Although the origin of the simian primates is obscure, new fossil evidence could push it further back by at least 10 million years. Such uncertainties reflect the low sampling level of the primate fossil record, which can potentially also lead to underestimation of times of origin within the primate tree.

Animals

Plasma cortisol transport and primate evolution.

Primates have diverged into three major evolutionary groups: prosimians, Old World primates, and New World primates; the last group is distinguished by high circulating cortisol concentrations and resistance to the action of glucocorticoids. We have studied a large spectrum of primate species within these groups to characterize the phylogenetic relationships of cortisol-binding globulin (CBG) among them. The CBG in each species was found to be glycosylated, as judged from lectin interactions, and to exhibit an electrophoretic mobility similar to that of human CBG. Although the CBG affinity for cortisol differed among species, the effects of changes in temperature on the CBG affinity were similar. Strikingly, the CBG-binding capacity of plasma in the New World primates was 1/10th to 1/100th those in the Old World primates and prosimians, while the CBG-binding affinity for cortisol was lower. The reduced capacity and affinity of CBG result in a markedly higher fraction of unbound plasma cortisol in the New World primates than in the Old World primates or the prosimian species examined. This evolutionary pattern of CBG may be a compensatory mechanism for the target organ resistance to glucocorticoids that characterizes the New World monkeys.

Animals

Non-human primates used in studies of periodontal disease pathogenesis: a review of the literature.

The inability to examine initiation and progression of periodontal disease and to assess certain therapies in humans has led to a great interest in the use of animal models in periodontal research. Some of the most prominent animals used are non-human primates. This article reviews the characteristics of non-human primate models in periodontal health, in the transition from health to gingivitis to periodontitis, and in experimental gingivitis and periodontitis. Where possible, the results of these studies are compared with results from human studies. Only a few studies have compared in detail the anatomy, physiology, immunology, and tissue interactions in monkeys with those of humans. With the exceptions of differences and variations in size of the dentition, the number of each tooth type as well as larger canines, presence of diastemata between anterior teeth, and an edge-to-edge relationship of the incisors, the dental and periodontal anatomy of non-human primates seem quite similar to that of humans. Clinically healthy gingiva can be established and maintained in non-human primates, and gingivitis as well as periodontitis occur in these animals. It is possible to induce experimental periodontitis by placement of peri-dental silk ligatures or orthodontic elastics as well as by surgical removal of alveolar bone. Although the most appropriate model for studies of periodontal disease pathogenesis in non-human primates appears to involve the application of silk ligatures, some difficulties may occur in establishing periodontal break-down by using this model. Many clinical, histological, microbiological, and immunological characteristics of spontaneous and experimental marginal inflammation in most non-human primates are similar to those in humans. The most significant differences between small non-human primates and humans are the very limited number of lymphocytes and plasma cells in the inflammatory infiltrate of squirrel monkeys (Saimiri sciureus) and marmosets. Therefore, the use of squirrel monkeys and marmosets may not be appropriate in many studies of periodontal disease pathogenesis. The most significant microbial differences between macaque species and humans are a lower proportion of Actinomyces species, the presence of a catalase-producing Prevotella melaninogenica strain, and the high carrier rate for Actinobacillus actinomycetemcomitans in subgingival plaque of macaque species. The significance of these differences is presently unknown. It is concluded that the use of many non-human primate species due to the apparent close anatomic and biologic similarities to humans is appropriate in experimental studies of periodontal disease, provided the use of laboratory animals is requisite and lower species are not applicable.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Comparative sequence analysis of cytokine genes from human and nonhuman primates.

Two major issues severely limit the studies of human recombinant cytokines/growth factors in nonhuman primates. First, assays and reagents specific for the detection and quantitation of human cytokines do not all function when utilized to detect/quantitate the nonhuman primate cytokines. Second, although most of the human cytokines appear to induce similar, if not identical, biologic function when used with cells from nonhuman primates in vitro or in vivo, they invariably induce Ab responses in vivo, precluding their repeated and/or continued use in vivo. Our laboratory has thus initiated studies to clone, sequence, and prepare recombinant cytokines from nonhuman primates and to define assays and reagents for their detection and quantitation at the nucleic acid and protein level. The data that were derived from such studies show that the nonhuman primate cytokines IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 alpha, IL-12 beta, IL-15, IFN-alpha, IFN-gamma, and TNF-alpha share 93 to 99% homology at the nucleic acid and protein level with the human equivalents. The most prominent differences between human and nonhuman primate cytokine sequences were noted for IL-1 alpha/beta, IL-2, IL-8, IFN-alpha, IFN-gamma, and IL-12 beta. The aligned sequences of cytokines for human and several nonhuman primate species are provided herein, and a phylogenetic analysis of the published sequences of select cytokines from other species, along with those of the nonhuman primates, are described. In addition, comparative analysis of the relative bioactivity of our immunoaffinity-purified recombinant rhesus macaque IL-4, IL-15, and IFN-gamma with commercially available human recombinant cytokines is described herein.

Amino Acid Sequence

The neuroanatomical organization of pathways between the dorsal lateral geniculate nucleus and visual cortex in Old World and New World primates.

Pathways between the dorsal lateral geniculate nucleus (dLGN) and visual cortex in Old World (Macaca, Papio, Erythrocebus, Cercopithecus) and New World (Saimiri, Cebus) primates were studied after injections of horseradish peroxidase and H3 or S35 amino acids into the dLGN or visual cortex. Trans-synaptic autoradiography was also used to study these pathways after an injection of H3 proline-fucose into one eye. The subsequent autoradiographs of visual cortex showed that Old World primates have separate eye inputs (ocular dominance columns) in the striate cortex, whereas New World monkeys have overlapping or non-separated eye inputs. In both primate groups the geniculocortical input to layer IVA formed a pattern which resembled a honeycomb in tangential sections, unlike the solidly labeled layer IVC. Also common to the two primate groups was a projection from dLGN to layer VI. There was no dLGN projection to any prestriate area in any of the primates. However, after an injection limited to the prestriate cortex of Macaca, light autoradiographic labeling was seen in the interlaminar zones and the magnocellular and S laminae, demonstrating a prestriate-dLGN pathway. Our results indicate that the primate visual system differs significantly from the cat in having no dLGN projection to area 18. There are also signficant differences between primates in the level at which the possibility of binocularity (of an excitatory nature) first occurs in the striate cortex because in the species studied thus far with neuroanatomical methods, Old World primates have ocular dominance columns in layer IV but most New World monkeys lack them.

Animals

The topography of primate retina: a study of the human, bushbaby, and new- and old-world monkeys.

The distribution of ganglion cells has been studied in the retinas of four primates: the prosimian bushbaby, the New-World squirrel monkey, the Old-World crab-eating cynamolgous monkey, and the human. The sizes of ganglion cell somas were also measured at a number of retinal locations and compared with similar measurements in the cat retina to test for the presence in primates of retinal specializations such as the visual streak, and for gradients in retinal structure, such as that between temporal and nasal retina. In all four primates, ganglion cell somas in peripheral retina ranged considerably in diameter (6-16 micrometer in the bushbaby, 8-22 micrometer in the squirrel monkey, 8-23 micrometer in the cynamolgous monkey, 8-26 micrometer in the human). It seems likely that the strong physiological correlates of soma size which have been described among cat retinal ganglion cells and among the relay cells of the macaque lateral geniculate nucleus are generally present in primates. In all four primates, evidence was also obtained of a visual streak specialization; the isodensity lines in ganglion cell density maps were horizontally elongated, and small-bodied ganglion cells were relatively more common in the region of the proposed streak than in other areas of peripheral retina. However, the visual streak seems less well developed than in the cat; among the four primate species examined it was best developed in the bushbaby, at least as assessed by the shape of the isodensity lines. All four primates showed a clear foveal specialization, but this feature seemed least developed in the bushbaby. At the fovea, ganglion cells are smaller in soma size than in peripheral retina; they also seemed more uniform in size, although some distinctly larger cells persist in the human and bushbaby. Soma size measurements also provided evidence of a difference between nasal and temporal areas of peripheral retina comparable to that reported for the cat and other species. Thus the primate retinas examined show features, such as the foveal specialization, which seem unique to them among mammals. They also show features, such as nasal-temporal differences in ganglion cell size, and (though weakly developed) a visual streak, which they have in common with other mammals with widely different phylogenetic histories.

Animals

Comparison of canine and non-human primate animal models for periodontal regenerative therapy: results following a single administration of PDGF/IGF-I.

Two commonly used animal models for evaluating putative periodontal regenerative therapies are the beagle dog model with natural periodontal disease and the non-human primate with ligature-induced attachment loss. The host response, microbiology, and skeletal rates of remodeling of these two models are summarized. In addition, the results of experiments comparing the healing response to periodontal surgery with and without concurrent use of the combination of platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) in these models are presented. At 1 month, PDGF/IGF-I administration resulted in a 64.1% and 51.4% increase in new attachment formation in the non-human primate and canine, respectively, while controls (surgery plus placebo) demonstrated 34.1% and 8.6% increases in new attachment formation in the non-human primate and canine models, respectively. Further, application of PDGF/IGF-I stimulated 21.6% and 65% osseous defect fill in the non-human primate and canine, respectively, while controls demonstrated 8.5% and 14.5% osseous defect fill in the non-human primate and canine, respectively. The osseous response in the canine appears greater than that of the non-human primate, and the new attachment formation was more substantial in the non-human primate than the canine. However, in general these data demonstrate a high degree of consistency in the effects of PDGF/IGF-I in promoting periodontal regeneration. Positive results in these two models--the dog with natural periodontal disease and the non-human primate with ligature-induced attachment loss--justify human clinical trial testing of a putative regenerative therapy.

Alveolar Bone Loss

Selective myocardial cell necrosis in nonhuman primates.

A retrospective study was performed to describe the histologic stages of selective myocardial cell necrosis (SMCN) in nonhuman primates, and to compare the incidence of SMCN in two groups of nonhuman primates. Myocardial tissues taken at the time of autopsy from 50 primates at an experimental center were compared with similar tissues from 50 primates housed in a breeding colony. SMCN was confirmed in 20% of the experimental primates and 30% of the breeding primates, proportions that were not significantly different. The incidence and histologic characteristics of SMCN in nonhuman primates were similar to those described in humans, and resembled the lesion produced in experimental primates by administration of catecholamines of by hypokalemia.

Animals

Evolution of the primate cytochrome c oxidase subunit II gene.

We examined the nucleotide and amino acid sequence variation of the cytochrome c oxidase subunit II (COII) gene from 25 primates (4 hominoids, 8 Old World monkeys, 2 New World monkeys, 2 tarsiers, 7 lemuriforms, 2 lorisiforms). Marginal support was found for three phylogenetic conclusions: (1) sister-group relationship between tarsiers and a monkey/ape clade, (2) placement of the aye-aye (Daubentonia) sister to all other strepsirhine primates, and (3) rejection of a sister-group relationship of dwarf lemurs (i.e., Cheirogaleus) with lorisiform primates. Stronger support was found for a sister-group relationship between the ring-tail lemur (Lemur catta) and the gentle lemurs (Hapalemur). In congruence with previous studies on COII, we found that the monkeys and apes have undergone a nearly two-fold increase in the rate of amino acid replacement relative to other primates. Although functionally important amino acids are generally conserved among all primates, the acceleration in amino acid replacements in higher primates is associated with increased variation in the amino terminal end of the protein. Additionally, the replacement of two carboxyl-bearing residues (glutamate and aspartate) at positions 114 and 115 may provide a partial explanation for the poor enzyme kinetics in cross-reactions between the cytochromes c and cytochrome c oxidases of higher primates and other mammals.

Amino Acid Sequence

Coraco-clavicular joint: normal variant in humans. A radiographic demonstration in the human and non-human primate.

The coraco-clavicular joint is a true synovial joint that may become painful in some patients after trauma. Among the descriptions of this entity is the assertion that the coraco-clavicular joint is routinely seen in gorillas and gibbons. We undertook to assess the incidence of this variant among gorillas, gibbons, and other non-human primates. All available radiographs of large primates performed at the International Wildlife Conservation Park/Bronx Zoo (IWCP) over the past 10 years were reviewed by a musculoskeletal radiologist (human radiology). All radiographs were taken during the normal clinical care of the non-human primate population of the IWCP and are a part of each animal's clinical record. Eighty-one non-human primate radiographs were suitable for study as they contained the region of interest. The 81 radiographic examinations included 14 different species of non-human primates. The coraco-clavicular joint was seen in 4 out of 9 silver-leaf langur, 2 out of 8 lowland gorilla, and in 1 out of 6 white-handed gibbon. In all non-human primate cases where the coraco-clavicular joint occurred, it was bilateral. In 1 out of 8 mandrill, there were very wide distal clavicular ends that articulated both with the coracoid and with the acromion. The coraco-clavicular joint differs from an ossified coraco-clavicular ligament. The radiographic appearance is characteristic and is found in both humans and some non-human primate species. It may rarely become painful following trauma. When symptomatic in humans, resection of this anomalous articulation is curative.

Acromioclavicular Joint

Effects of environmental conditions on the psychological well-being of primates: a review of the literature.

Amendments made to the Animal Welfare Act in 1985 require primate researchers to provide "a physical environment adequate to promote the psychological well-being of primates". Regulations have not yet been promulgated, in part because "the psychological well-being" of primates is extremely difficult to define. Ideally, those regulations would be based upon observable changes in behavior rather than assumed psychological changes. Regardless, new primate care regulations pertaining to social environment, cage size, exercise and other forms of environmental enrichment are anticipated. A review of the literature suggests that there is little scientific data to support changing existing regulations. For instance, although it is clear that total social isolation in very young primates can be behaviorally devastating in terms of normal social behaviors, there are few, if any, demonstrable adverse effects of individual housing in adult primates. On the other hand, group housing, particularly with groups changing frequently in composition, increases aggression, trauma and disease transmission. In addition, existing research suggests there are important species differences in terms of social preferences. It is impossible to justify an increase in cage size based upon the available literature. An additional practical consideration is that any change in cage size requirements will necessitate replacement of current primate housing on a national level, an enormously expensive proposition. Regarding environmental enrichment, research suggests that providing a naturalistic environment is not as critical as arranging dynamic events that are contingent upon behavior. However, new research is necessary to specify the types of environmental enrichment that are valuable and appropriate before useless, even damaging, and expensive changes are mandated.

Animal Welfare

Brain weight and life-span in primate species.

In haplorhine primates (tarsiers, monkeys, apes, and humans), there is a significant correlation between brain weight and maximum life-span when the effect of body size is removed. There is also a significant correlation in haplorhine primates between brain weight and female age at first reproduction. For strepsirhine primates (lorises and lemurs), there are no significant correlations between brain weight and either life-span or female reproductive age when the effect of body size is removed. This lack of correlation in strepsirhine primates may be related to the fact that these primates are nocturnal and/or natives of the island of Madagascar, both of which conditions may reduce competition for resources and predation pressure. These findings suggest that in haplorhine primates the genetic systems controlling brain growth are linked to the systems governing the life cycle so that species with longer cycles have larger brains. When the effect of body weight is removed, leaf-eating haplorhines have significantly smaller brains and shorter lives than haplorhines with other diets. Harem-living haplorhines also have significantly smaller brains and shorter life-spans than troop-living haplorhines when the effect of body weight is removed. We also sought to test the rate-of-living hypothesis by determining whether primates with basal metabolic rates that are higher than would be expected for their body size have shorter maximum life-spans than would be expected for their body size. Metabolic rate is not correlated with life-span or female age at first reproduction when the effect of body size is removed.

Adrenal Glands

Evolutionary radiation of visual and olfactory brain systems in primates, bats and insectivores.

How brains have evolved in response to particular selection pressures is illuminated by ecological correlates of differences in brain structure among contemporary species. The focus of most comparative studies has been on the overall size of brains relative to body size, hence ignoring the ways in which selection operates on specific neural systems. Here we investigate evolutionary radiations in the size of visual and olfactory brain structures within three orders of mammals: primates, bats and insectivores. The comparative relationships within these three orders show both similarities and differences. After removal of the allometric effect of overall brain size, the sizes of different structures within each sensory modality are positively correlated in all three orders. Correlations between visual and olfactory structures, however, are negative in primates, negative but non-significant in insectivores, and positive in bats. In both primates and insectivores, nocturnal lineages tend to have larger olfactory structures than do diurnal or partly diurnal lineages, and among the primates diurnal lineages have larger striate visual cortexes. Hence the apparent trade-off between vision and olfaction in primates seems to be related to the divergence of nocturnal and diurnal forms. However, negative correlations between visual and olfactory structures were also found when nocturnal strepsirhines and diurnal haplorhines were analysed separately, suggesting that ecological variables in addition to activity timing may be significant. Indeed, there were also associations with diet: frugivory was associated with enlargements of the geniculostriate visual system in diurnal primates, enlargements of olfactory structures in nocturnal primates, and possibly enlargements of both in bats. Further ecological associations were found within insectivores: aquatic lineages had smaller olfactory structures than in their non-aquatic counterparts, and fossorial lineages had smaller optic nerves than in non-fossorial forms. We conclude that activity timing, diet and habitat have each played a role in the evolutionary radiation of mammalian sensory systems, but with varying effects in the different taxa. Some of the associations between ecology and sensory systems suggest alternative explanations for correlates of overall brain size, which have in the past commonly been interpreted in terms of selection on intelligence.

Adaptation, Biological