Serotonin transporter gene-linked polymorphic region: Allele distributions in relationship to body weight and in anorexia nervosa

Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals.     

The human SDF1 gene polymorphism is located on a mutational hot spot that was identified by the hominoid genome study.

Nucleotide sequences of a part of the stromal cell-derived factor-1 (SDF-1) gene 3' untranslated region were studied among hominoids (chimpanzees, gorillas, orangutans and gibbons). An identical sequence to the human SDF1-3'G allele was found in chimpanzees and gibbons, whereas that to the 3'A allele was found in gorillas. Based on the sequence data and the hominoid phylogenetic relation, it was suggested that an adenine nucleotide at nucleotide position (np) 801 in humans and gorillas was independently introduced into each lineage after the specific divergence and an ancestral hominoid sequence of this site (np 799-802) was deduced as CCGG. The present data showing a mutational hot spot on this site suggest the possible presence of multiple origins of the worldwide distribution of the SDF1-3'A allele in humans.     

Comparative analysis of estrogen receptor gene polymorphisms in apes

Polymorphic microsatellite repeats in the promoter region of estrogen receptor α gene (ESRα and the intron 6 region of estrogen receptor β gene (ESRβ) have been reported in human populations. To examine the evolutional state of both repeats, we surveyed the corresponding regions in DNA sequences from the following great apes and gibbons: 56 chimpanzees, 3 bonobos, 16 gorillas, 20 orangutans and 60 gibbons (four species: 17 of Hylobates agilis, 11 of H. lar, 15 of H. muelleri, and 17 of H. syndactylus). In the corresponding region of the TA repeat of human ESRα, chimpanzees and bonobos had two motifs in the repeat tract, (TA)_7–9 and (CA)_4–6. Gorillas had the (TA)_9–10 repeat tracts and orangutans had monomorphic (TA)₇ repeats. Although all great apes maintained the TA expansion, all gibbon sequences contained (TA)₂, implying that the CA dinucleotide expansion arose in the ancestor of chimpanzees and bonobos. The nucleotide sequences of ESRβ showed a very complex repeat pattern in apes. The human sequences had a non-variable preceding sequence at (CA) _n , (GA)₂(TA)₈(CA)₄(TA). In apes that region included {(TA) _n (CA) _n } _n . Gibbon sequences included (TATG) _n and (TATC) _n and no regular construction was observed. A deletion event in the reverse primer site seems to have occurred in the orangutan lineage. In addition, a great diversity of allele length was detected in each gibbon species.     

Molecular evolution of the psi eta-globin gene locus: gibbon phylogeny and the hominoid slowdown

An 8.4-kb genomic region spanning both the psi eta-globin gene locus and flanking DNA was sequenced from the common gibbon (Hylobates lar). In addition, sequencing of the entire orthologous region from galago (Galago crassicaudatus) was completed. The gibbon and galago sequences, along with published orthologous sequences from 10 other species, were aligned. These noncoding nucleotide sequences represented four human alleles, four apes (chimpanzee, gorilla, organgutan, and gibbon), an Old World monkey (rhesus monkey), two New World monkeys (spider and owl monkeys), tarsier, two strepsirhines (galago and lemur), and goat. Divergence and maximum parsimony analyses of the psi eta genomic region first groups humans and chimpanzees and then, at progressively more ancient branch points, successively joins gorillas, orangutans, gibbons, Old World monkeys, New World monkeys, tarsiers, and strepsirhines (the lemuriform-lorisiform branch of primates). This cladistic pattern supports the taxonomic grouping of all extant hominoids into family Hominidae, the division of Hominidae into subfamilies Hylobatinae (gibbons) and Homininae, the division of Homininae into tribes Pongini (orangutans) and Hominini, and the division of Hominini into subtribes Gorillina (gorillas) and Hominina (chimpanzees and humans). The additional gibbon and galago sequence data provide further support for the occurrence of a graded evolutionary-rate slowdown in the descent of simian primates, with the slowing rate being more pronounced in the great-ape and human lineages than in the gibbon or monkey lineages. A comparison of global versus local molecular clocks reveals that local clock predictions, when focused on a specific number of species within a narrow time frame, provide a more accurate estimate of divergence dates than do those of global clocks.     

Evolution of alpha 2-fucosyltransferase genes in primates: relation between an intronic Alu-Y element and red cell expression of ABH antigens

Coding sequences of the paralogous FUT1 (H), FUT2 (Se), and Sec1 alpha 2-fucosyltransferase genes were obtained from different primate species. Analysis of the primate FUT1-like and FUT2-like sequences revealed the absence of the known human inactivating mutations giving rise to the h null alleles of FUT1 and the se null alleles of FUT2. Therefore, most primate FUT1-like and FUT2-like genes potentially code for functional enzymes. The Sec1-like gene encodes for a potentially functional alpha 2-fucosyltransferase enzyme in nonprimate mammals, New World monkeys, and Old World monkeys, but it has been inactivated by a nonsense mutation at codon 325 in the ancestor of humans and African apes (gorillas, chimpanzees). Human and gorilla Sec1's have, in addition, two deletions and one insertion, respectively, 5' of the nonsense mutation leading to proteins shorter than chimpanzee Sec1. Phylogenetic analysis of the available H, Se, and Sec1 mammalian protein sequences demonstrates the existence of three clusters which correspond to the three genes. This suggests that the differentiation of the three genes is rather old and predates the great mammalian radiation. The phylogenetic analysis also suggests that Sec1 has a higher evolutionary rate than FUT2 and FUT1. Finally, we show that an Alu-Y element was inserted in intron 1 of the FUT1 ancestor of humans and apes (chimpanzees, gorillas, orangutans, and gibbons); this Alu-Y element has not been found in monkeys or nonprimate mammals, which lack ABH antigens on red cells. A potential mechanism leading to the red cell expression of the H enzyme in primates, related to the insertion of this Alu-Y sequence, is proposed.     

Species association of hepatitis B virus (HBV) in non-human apes; evidence for recombination between gorilla and chimpanzee variants

Hepatitis B virus (HBV) infections are widely distributed in humans, infecting approximately one third of the world's population. HBV variants have also been detected and genetically characterised from Old World apes; Gorilla gorilla (gorilla), Pan troglodytes (chimpanzee), Pongo pygmaeus (orang-utan), Nomascus nastusus and Hylobates pileatus (gibbons) and from the New World monkey, Lagothrix lagotricha (woolly monkey). To investigate species-specificity and potential for cross species transmission of HBV between sympatric species of apes (such as gorillas and chimpanzees in Central Africa) or between humans and chimpanzees or gorillas, variants of HBV infecting captive wild-born non-human primates were genetically characterised. 9 of 62 chimpanzees (11.3%) and two from 11 gorillas (18%) were HBV-infected (15% combined frequency), while other Old world monkey species were negative. Complete genome sequences were obtained from six of the infected chimpanzee and both gorillas; those from P. t .ellioti grouped with previously characterised variants from this subspecies. However, variants recovered from P. t. troglodytes HBV variants also grouped within this clade, indicative of transmission between sub-species, forming a paraphyletic clade. The two gorilla viruses were phylogenetically distinct from chimpanzee and human variants although one showed evidence for a recombination event with a P.t.e.-derived HBV variant in the partial X and core gene region. Both of these observations provide evidence for circulation of HBV between different species and sub-species of non-human primates, a conclusion that differs from the hypothesis if of strict host specificity of HBV genotypes.     

Serotonin Transporter Gene-Linked Polymorphism Affects Detection of Facial Expressions

Previous studies have demonstrated that the serotonin transporter gene-linked polymorphic region (5-HTTLPR) affects the recognition of facial expressions and attention to them. However, the relationship between 5-HTTLPR and the perceptual detection of others'' facial expressions, the process which takes place prior to emotional labeling (i.e., recognition), is not clear. To examine whether the perceptual detection of emotional facial expressions is influenced by the allelic variation (short/long) of 5-HTTLPR, happy and sad facial expressions were presented at weak and mid intensities (25% and 50%). Ninety-eight participants, genotyped for 5-HTTLPR, judged whether emotion in images of faces was present. Participants with short alleles showed higher sensitivity (d′) to happy than to sad expressions, while participants with long allele(s) showed no such positivity advantage. This effect of 5-HTTLPR was found at different facial expression intensities among males and females. The results suggest that at the perceptual stage, a short allele enhances the processing of positive facial expressions rather than that of negative facial expressions.     

Strategies for the Use of Fallback Foods in Apes

Researchers have suggested that fallback foods (FBFs) shape primate food processing adaptations, whereas preferred foods drive harvesting adaptations, and that the dietary importance of FBFs is central in determining the expression of a variety of traits. We examine these hypotheses in extant apes. First, we compare the nature and dietary importance of FBFs used by each taxon. FBF importance appears greatest in gorillas, followed by chimpanzees and siamangs, and least in orangutans and gibbons (bonobos are difficult to place). Next, we compare 20 traits among taxa to assess whether the relative expression of traits expected for consumption of FBFs matches their observed dietary importance. Trait manifestation generally conforms to predictions based on dietary importance of FBFs. However, some departures from predictions exist, particularly for orang-utans, which express relatively more food harvesting and processing traits predicted for consuming large amounts of FBFs than expected based on observed dietary importance. This is probably due to the chemical, mechanical, and phenological properties of the apes’ main FBFs, in particular high importance of figs for chimpanzees and hylobatids, compared to use of bark and leaves—plus figs in at least some Sumatran populations—by orang-utans. This may have permitted more specialized harvesting adaptations in chimpanzees and hylobatids, and required enhanced processing adaptations in orang-utans. Possible intercontinental differences in the availability and quality of preferred and FBFs may also be important. Our analysis supports previous hypotheses suggesting a critical influence of the dietary importance and quality of FBFs on ape ecology and, consequently, evolution.     

Distances éntre l'homme et les singes anthropoïdes basées sur la mobilité électrophorétique des protéines et enzymes

Electrophoretic mobilities of ten homologous serum proteins and enzymes in Man and anthropoid apes led to estimations of the genetic distances between five species (Homo, Pan, Gorilla, Pongo and Symphalangus). The separation of the Symphalangus (Siamang) lineage from that leading to the great apes and Man is obvious. Less evident is the cluster containing only humans and chimpanzees, and also the fact that orang-utans are placed closer to Man than gorillas.     

Allelic variation of the dopamine receptor D4 gene polymorphic region in gibbons

We examined the tandem repeat sequence of the dopamine receptor D4 (DRD4) gene in 73 individuals derived from 8 species of gibbons (genusHylobates) in an attempt to assess the variability of this gene in gibbon species.H. syndactylus (subgenusSymphalangus) andH. concolor (subgenusNomascus), which were inferred to have diverged at an early time within the family Hylobatidae, shared only long repeat (7–8) alleles. On the other hand, DRD4 was highly polymorphic in gibbons of the subgenusHylobates, with 4-, 5-, 6-, 7-, and 8-repeat alleles being recognized. In this subgenus, 4- and 5-repeat alleles were found in the species distributed mainly in the southern islands such as Sumatra, Java, and Borneo but not in the species inhabiting the Asian continent. Sequence analysis indicated that the repeat structure of the gibbon DRD4 gene was quite complex but most of the 48-bp units could be classified into several groups across the species based on sequence similarities. However, the sequence of the 7-repeat allele ofH. muelleri was unique, since the repeat units had low similarities to other units of gibbons.     

Hepatic expression of cytochrome P450 enzymes in non‐human primate species

Cytochromes P450 (P450) largely remain to be characterized in great apes. Comparative immunochemical detection of drug metabolizing forms of P450s 1A, 2A, 2B, 2C, 2D, 2E, 2J, 3A, 4A, and 4F in liver microsomes from chimpanzees, gorillas, orangutans, gibbons, cynomolgus and rhesus macaques, and common marmosets were carried out.     

No association between the serotonin transporter-linked promoter region polymorphism and either schizophrenia or density of the serotonin transporter in human hippocampus.

BACKGROUND: Allelic association case-control analysis of a deletion/insertion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has suggested associations with unipolar disorder, bipolar disorder, depression, and Alzheimer's disease. Moreover, the heterozygous long form of the 5-HTTLPR has been associated with increased levels of mRNA for the serotonin transporter (5-HTT) and increased serotonin uptake in lymphoblastic cell lines. This study attempts to determine whether there is an association between 5-HTTLPR genotype and schizophrenia or the binding of [3H]paroxetine to the human hippocampal 5-HTT. MATERIALS AND METHODS: DNA from the cerebellum from 58 schizophrenic and 62 control subjects was used to genotype the 5-HTTLPR. In addition, the relationship between 5-HTTLPR genotype and the affinity and density of [3H]paroxetine binding to the hippocampal 5-HTT was assessed. RESULTS: There were no associations between 5-HTTLPR allotype or genotype and/or the parameters of [3H]paroxetine binding to the hippocampal 5-HTT. CONCLUSIONS: Our data suggest that 5-HTTLPR genotype neither confers an increased susceptibility for schizophrenia nor dictates the expression of the 5-HTT in the human hippocampus.     

Quantitative and functional studies on the hands of the anthropoidea. I. The Hominoidea

The hands of the Hominoidea evidence four adaptive modes which distinguish the lesse apes (Hylobatidae), the orangutan (Pongo), the African apes (Pan), and man (Homo) from one another. The hands of the apes consist of compromises between manipulatory and locomotor functions because selection has operated for precision of grip as well as for special locomotor mechanisms. The human hand is almost totally devoted to manipulation. The hands of gibbons, orangutans and the African apes differ in many features that may be correlated with locomotion. The gibbons and siamang are specially adapted for ricochetal arm-swinging. The great apes possess morphological adaptations for arboreal foraging and climbing distinct from those of the hylobatids. In addition, the African apes have become secondarily adapted for terrestrial quadrupedal locomotion. Many features that distinguish the hands of chimpanzees and gorillas may be associated with the development of efficient knuckele-walking propulsive and support mechanisms.     

Apes and Tricksters: The Evolution and Diversification of Humans’ Closest Relatives

The evolutionary history of humans comprises an important but small branch on the larger tree of ape evolution. Today’s hominoids—gibbons, orangutans, gorillas, chimpanzees, and humans—are a meager representation of the ape diversity that characterized the Old World from 23–5 million years ago. In this paper, I briefly review this evolutionary history focusing on features important for understanding modern ape and human origins. As the full complexity of ape evolution is beyond this review, I characterize major geographic, temporal, and phylogenetic groups using a few flagship taxa. Improving our knowledge of hominoid evolution both complicates and clarifies studies of human origins. On one hand, features thought to be unique to the human lineage find parallels in some fossil ape species, reducing their usefulness for identifying fossil humans. On the other hand, the Miocene record of fossil apes provides an important source for generating hypotheses about the ancestral human condition; this is particularly true given the dearth of fossils representing our closest living relatives: chimpanzees and gorillas.     

Food Preferences Among Captive Western Gorillas (Gorilla gorilla gorilla) and Chimpanzees (Pan troglodytes)

I used a zoological park setting to address food preferences among gorillas (Gorilla gorilla gorill) and chimpanzees (Pan troglodytes). Gorillas and chimpanzees are different sizes, and consequently, have been traditionally viewed as ecologically distinct. Sympatric western gorillas and chimpanzees have proved difficult to study in the wild. Limited field data have provided conflicting information about whether gorillas are fundamentally different from chimpanzees in diet and behavior. Fruit eating shapes the behavior of most apes, but it is unclear whether the large-bodied gorillas are an exception to this rule, specifically whether they are less selective and more opportunistic fruit eaters than chimpanzees are. My research provides experimental observational data to complement field data and to better characterize the diets and food preferences of the African apes. During laboratory research at the San Francisco Zoological Gardens, I examined individual and specific differences in food preferences of captive gorillas and chimpanzees via experimental paired-choice food trials with foods that varied in nutritional content. During the study, I offered 2500 paired-food choices to 6 individual gorillas and 2000 additional pairs to them as a group. I also proffered 600 food pairs to 4 individual chimpanzees. Despite expectations of the implications of body size differences for diet, gorillas and chimpanzees exhibited similar food preferences. Both species preferred foods high in non-starch sugars and sugar-to-fiber ratios, and low in total dietary fiber. Neither species avoided foods containing tannins. These data support other suggestions of African apes sharing a frugivorous adaptation.     

Evolution of a VNTR located within the promoter region of the thiopurine methyltransferase gene: inferences from population and sequence data

The promoter region of the human thiopurine methyltransferase (TPMT) gene contains a variable number of tandem repeats (VNTR) with three kind of motifs (A, B, and C) differing by the length of the unit core and nucleotide sequence. We have studied the structural variation within the VNTR alleles in two human populations and in samples from gorillas and chimpanzees. In humans, no intermingling of motifs was detected within the VNTR, and the sequences of the three core motifs remained remarkably unchanged, differences between alleles corresponding essentially to variations in the number of A and B repeats. The variation pattern in humans is consistent with an interpretation in which two contiguous genetic units (repeats A and B) behave evolutionarily according to the stepwise mutation model, as inferred from the population distribution profiles and from the molecular phylogenetic relationships among the VNTR alleles. However, the observation of a strong negative correlation between the numbers of A and B repeats also suggests that the regularity and/or independence of the mutational process has been disrupted to some extent by interactions between the A and B stretches. Selective pressure (the VNTR plays some role, although minor, in the TPMT function) or biased mutation are possible explanations. In gorillas and chimpanzees, several A-, B-, or C-like motifs were detected, but their arrangement within the VNTR alleles did not followed the regular pattern registered in humans and, particularly for the B-like motifs, a considerable sequence hypervariability was registered. Furthermore, the structural differences among non-human alleles were sufficiently numerous to render more plausible the assumption of the infinite allele model.     

Palato-facial comparison ofDryopithecus (Proconsul) with extant catarrhines

Multivariate shape analysis of 15 palato-facial measurements of the RusingaD. africanus and MorotoD. major specimens in comparison with apes and monkeys fails to support the hypothesis of special relationship between the dryopithecine species and extant African pongids. TheD. africanus shares with gibbons and cercopithecoids the primitive catarrhine metrical pattern, while chimpanzees and gorillas show a different, derived pattern. TheD. major shows partial convergence on the shape pattern typifying gorillas.     

Hand preferences in captive gorillas,orang-utans and gibbons

Hand preference was assessed in 12 gorillas (Gorilla gorilla gorilla), 13 orang-utans (Pongo pygmaeus abelii), and 9 gibbons (Hylobates lar) by using a floor retrieval task and a mesh retrieval task. Hand preference was also assessed in 8 gorillas and 8 orang-utans by using a task involving the unfastening of a hasp. A bipedal requirement during testing (mesh retrieval task) facilitated detection of hand preferences. A significant left-hand preference was found for the gibbons with 6 of 6 gibbons preferring their left hand on the mesh retrieval task. Similarly, a significant right-hand preference was found for the gorillas with 10 of 12 gorillas preferring their right hand on the mesh retrieval task. The data for the orang-utan suggest a bimodal distribution on all tasks. Since the gibbon and gorilla in the wild engage in bipedal locomotion more frequently than the orangutan, one possible interpretation for these results correlates the degree of bipedal behavior of a species in its natural environment with its readiness to exhibit a unilateral population-level hand preference.