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C J Jolly

Publications and source records attributed to C J Jolly.

At least 19 recordsLinked to original sources

Comparative postcranial body shape and locomotion in Chlorocebus aethiops and Cercopithecus mitis.

Body weight and length, chest girth, and seven postcranial limb segment lengths are compared between two guenon species, Chlorocebus (Cercopithecus) aethiops (vervets) and Cercopithecus mitis (blue monkeys), exhibiting different habitual locomotor preferences. The subjects, all adults, were wild caught for a non-related research project (Turner et al. [1986] Genetic and morphological studies on two species of Kenyan monkeys, C. aethiops and C. mitis. In: Else JG, Lee PC, editors. Primate evolution, proceedings of the Xth International Congress of Primatology, Cambridge. London). The morphological results are interpreted within the context of previously published observations of primate locomotion and social organization. The sample is unique in that the body weight of each individual is known, allowing the effects of body-size scaling to be assessed in interspecific and intersexual comparisons. C. mitis has a significantly (P < 0.05) greater body weight and trunk length than C. aethiops. A shorter trunk may function to reduce spinal flexibility for ground-running in the latter. Proximal limb segments (arm and thigh) are significantly greater in C. mitis, reflecting known adaptations to committed arboreal quadrupedal locomotion. By contrast, relative distal limb segments (forearm, crus, and foot) are significantly longer in C. aethiops, concordant with a locomotor repertoire that includes substantial terrestrial quadrupedalism, in addition to arboreal agility, and also the requisite transition between ground and canopy. Although normally associated with arboreal monkeys, greater relative tail length occurs in the more terrestrial vervets. However, because vervets exploit both arboreal and terrestrial habitats, a longer tail may compensate for diminished balance during arboreal quadrupedalism resulting from the greater "brachial" and "crural" indices that enhance their ground quadrupedalism. Most interspecific differences in body proportions are explicable by differences in locomotor modalities. Some results, however, contradict commonly held "tenets" that relate body size and morphology exclusively to locomotion. Generally associated with terrestriality, sexual dimorphism (male/female) is greater in the more arboreal blue monkeys. A more intense, seasonal mating competition may account for this incongruity.

Animals↗

In vivo and in vitro studies of immunoglobulin gene somatic hypermutation.

Following antigen encounter, two distinct processes modify immunoglobulin genes. The variable region is diversified by somatic hypermutation while the constant region may be changed by class-switch recombination. Although both genetic events can occur concurrently within germinal centre B cells, there are examples of each occurring independently of the other. Here we compare the contributions of class-switch recombination and somatic hypermutation to the diversification of the serum immunoglobulin repertoire and review evidence that suggests that, despite clear differences, the two processes may share some aspects of their mechanism in common.

Animals↗

A proper study for mankind: Analogies from the Papionin monkeys and their implications for human evolution.

This paper's theme is that analogies drawn from the cercopithecine tribe Papionini, especially the African subtribe Papionina (baboons, mangabeys, and mandrills), can be a valuable source of insights about the evolution of the human tribe, Hominini, to complement homologies found in extant humans and/or African apes. Analogies, involving a "likeness of relations" of the form "A is to B, as X is to Y," can be usefully derived from nonhomologous (homoplastic) resemblances in morphology, behavior, ecology, or population structure. Pragmatically, the papionins are a fruitful source of analogies for hominins because they are phylogenetically close enough to share many basic attributes by homology, yet far enough that homoplastic modifications of these features are easily recognized as such. In "The Seedeaters," an analogy between Theropithecus among baboons and Australopithecus africanus among hominines was the source of a widely discussed (and often misrepresented) diet-based scenario of hominin origins that explained previously unassociated hominin apomorphies, interpreted basal hominins as nonhuman rather than prehuman primates, and accommodated a basal hominin adaptive radiation of at least two lines. Current usage recognizes an even more extensive evolutionary radiation among the basal hominins, originating no earlier than about 7 ma, with multiple lineages documented or inferred by 2.5 ma. Although multilineage clades (especially the Paranthropus clade) within this complex are widely recognized, and emerge from sophisticated, parsimony-based analyses, it is suspected that in many cases, developmental or functional homoplasies are overwhelming the phylogenetic signal in the data. The papionin analogy (specifically the splitting of the traditional, morphology-based genera Cercocebus and Papio mandated by molecular evidence) illustrates the power of these factors to produce erroneous cladograms. Moreover, the rapid deployment of basal hominins across varied African habitats was an ideal scenario for producing morphologically undetectable homoplasy. There seems to be no foolproof way to distinguish, a priori, homologous from homoplastic resemblances in morphology, but one pragmatic strategy is to severely censor the datset, retaining only resemblances or differences (often apparently trivial ones) that cannot be reasonably explained on the basis of functional resemblance or difference, respectively. This strategy may eliminate most morpological data, and leave many fossil taxa incertae sedis, but this is preferable to unwarranted phylogenetic confidence. Another source of phylogenetic uncertainty is the possibility of gene-flow by occasional hybridization between hominins belonging to ecologically and adaptively distinct species or even genera. Although the evidence is unsatisfactorily sparse, it suggests that among catarrhines generally, regardless of major chromosomal rearrangements, intersterility is roughly proportional to time since cladogenetic separation. On a papionin analogy, especially the crossability of Papio hamadryas with Macaca mulatta and Theropithecus gelada, crossing between extant hominine genera is unlikely to produce viable and fertile offspring, but any hominine species whose ancestries diverged less than 4 ma previously may well have been able to produce hybrid offspring that could, by backcrossing, introduce alien genes with the potential of spreading if advantageous. Selection against maladaptive traits would maintain adaptive complexes against occasional genetic infiltration, and the latter does not justify reducing the hybridizing forms to a conspecific or congeneric rank. Whether reticulation could explain apparent parallels in hominin dentition and brain size is uncertain, pending genetic investigation of these apparently complex traits. Widespread papionin taxa (such as Papio baboons and species-groups of the genus Macaca), like many such organisms, are distributed as a "patchwork" of nonoverlapping but often parapatric forms (allotaxa). Morphologically diagnosable, yet not reproductively isolated, most allotaxa would be designated species by the phylogenetic species concept, but subspecies by the biological species concept, and use of the term "allotaxa" avoids this inconsistency. A line of contact between allotaxa typically coincides with an ecotone, with neighboring allotaxa occupying similar econiches in slightly different habitats, and often exhibiting subtle, adaptive, morphological differences as well as their defining differences of pelage. "Hybrid zones," with a wide variety of internal genetic structures and dynamics, typically separate parapatric allotaxa. Current models attribute the formation and maintenance of allotaxa to rapid pulses of population expansion and contraction to and from refugia, driven by late Neogene climatic fluctuations. An overall similarity in depth of genetic diversity suggests that papionin taxa such as Papio baboons, rather than extant humans, may present the better analogy for human population structure of the "prereplacement" era. Neandertals and Afro-Arabian "premodern" populations may have been analogous to extant baboon (and macaque) allotaxa: "phylogenetic" species, but "biological" subspecies. "Replacement," in Europe, probably involved a rapidly sweeping hybrid zone, driven by differential population pressure from the "modern" side. Since the genetic outcome of hybridization at allotaxon boundaries is so variable, the problem of whether any Neandertal genes survived the sweep, and subsequent genetic upheavals, is a purely empirical one; if any genes passed "upstream" across the moving zone, they are likely to be those conferring local adaptive advantage, and markers linked to these. In general, extant papionin analogies suggest that the dynamics and interrelationships among hominin populations now known only from fossils are likely to have been more complex than we are likely to be able to discern from the evidence available, and also more complex than can be easily expressed in conventional taxonomic terminology.

Animals↗

Somatic hypermutation of immunoglobulin kappa transgenes: association of mutability with demethylation.

Following antigen encounter, immunoglobulin genes are diversified by somatic hypermutation. The mechanism by which this mutational process preferentially targets immunoglobulin genes is not known, but is likely linked to transcription. However, transcription is not sufficient to ensure mutability. Here, by polymerase chain reaction amplification of bisulfite-modified DNA, the pattern of demethylation within the Igkappa mutation domain is analysed and transgenes are used to identify an association between demethylation and mutability. In mice carrying an Igkappa transgene that is well transcribed but only poorly targeted for hypermutation, the mutated transgene copies have been demethylated within the mutation domain, whereas the methylated copies remain unmutated. Thus, the hypermutation mechanism only acts on immunoglobulin gene targets that are demethylated as well as transcribed, although transcription and demethylation do not themselves guarantee mutability.

Animals↗

Serum leptin levels in wild and captive populations of baboons (papio): implications for the ancestral role of leptin.

Leptin has emerged as the major lipostat, regulating adiposity by affecting feeding behavior and thermogenesis. Leptin levels in normal-weight Western humans and in captive rodents are 5-15 ng/ml. But evidence suggests that these levels are abnormally high and that leptin may have evolved as a more general metabolic signal, with its most robust effects at lower levels. If this is true, then wild, healthy animal populations should have lower levels of leptin than captive populations and Western Man. We examined leptin levels in wild, East African populations of baboons (Papio anubis, P. hamadryas, and anubis/hamadryas hybrids). Serum leptin levels averaged less than 1 ng/ml, and no differences occurred in leptin levels among the species. In wild baboons, serum leptin levels were highest in the youngest baboons, with a trend toward an inverse relation between dental age and serum leptin levels. In comparison, captive baboons had levels about three times higher than wild baboons, with a clear inverse relation between age and leptin levels. These results support the view that leptin evolved to be effective at low levels.

Aging↗

The contribution of somatic hypermutation to the diversity of serum immunoglobulin: dramatic increase with age.

Although somatic mutation contributes to the diversity of only a minor fraction of B cells in mouse spleen or blood, its contribution to the diversity of serum immunoglobulin is unknown. We have devised an immunoassay to monitor mutated antibodies in serum using a monoclonal antibody that recognizes a VK only when mutated at its major intrinsic hot spot. Mutation makes essentially no contribution to the diversity of endogenous serum IgM, IgG, or IgA in young mice. However, in response to environmental antigens, the titer of mutated immunoglobulin in T cell-proficient mice rises strikingly with age, such that the major proportion of serum immunoglobulin in adults is somatically mutated, with the mutation load in IgG being some 10-fold greater than in IgM.

Aging↗

An Alu insertion polymorphism in a baboon hybrid zone.

A novel polymerase chain reaction (PCR) primer pair was used to analyze the frequency of insertion of the first described, nonhuman, baboon-specific Alu repetitive element in populations from the Papio hamadryas anubis and the Papio hamadryas hamadryas subspecies, and from a number of anubis-hamadryas hybrids. The Alu insertion is found in intron 7 of the baboon lipoprotein lipase (LPL) gene. Each of the populations had different frequencies for the insertion, and the hybrids examined had a frequency intermediate to that of the parental populations. All hybrids and all P. h. anubis groups except the group of anubis sampled in 1973 exhibited higher-than-expected heterozygosity, while P. h. hamadryas and 1973 P. h. anubis showed lower-than-expected heterozygosity, supporting behavioral and other genetic observations of greater anubis outbreeding relative to hamadryas. This may include asymmetric introgression of the Alu insertion from hamadryas to the anubis population due to hybridization.

Alu Elements↗

Cerebrospinal fluid monoaminergic metabolites differ in wild anubis and hybrid (Anubis hamadryas) baboons: possible relationships to life history and behavior.

The article reports monoaminergic metabolite [homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)], values from the cerebrospinal fluid (CSF) of 27 wild baboons (Papio hamadryas) aged 40 to 140 months. Animals were either anubis, or anubis with hamadryas admixture; males of the latter subspecies generally have a reduced tendency to disperse from their natal groups. Overall, the values and interrelationships among the CSF monoamine metabolites resembled data reported from closely related, captive-housed animals. For example, age was significantly correlated with HVA concentrations (r = -60, p < .05), but not with the other metabolites. Notably, males characterized by hamadryas admixture had significantly higher concentrations of HVA, 5-HIAA, and MHPG (p < .05, respectively), a result possibly driven by differences in serotonergic activity. These data provide initial evidence that variation in central monoaminergic activity, as indicated by CSF monoamine metabolite concentrations, may reflect differences in behavior and life history that have taxonomic and, perhaps, evolutionary significance.

Age Factors↗

Multiple sequences from downstream of the J kappa cluster can combine to recruit somatic hypermutation to a heterologous, upstream mutation domain.

Recruitment of somatic hypermutation to the Ig kappa locus has previously been shown to depend on the enhancer elements, Ei/MAR and E3'. Here we show that these elements are not sufficient to confer mutability. However, hypermutation is effectively targeted to a chimeric beta-globin/Ig kappa transgene whose 5' end is composed of the human beta-globin gene (promoter and first two exons) and whose 3' end consists of selected sequences derived from downstream of the J kappa cluster (Ei/MAR, C kappa + flank and E3'). Thus, multiple downstream Ig kappa sequences (all derived from 3' of the J kappa cluster) can combine to recruit mutation to a heterologous mutation domain. The location of this hypermutation domain is defined by the position of the transcription start site and this applies even if the Ig kappa Ei/MAR is positioned upstream of the promoter. Hotspots within the mutation domain are, however, defined by local DNA sequence as evidenced by a new hotspot being created within the beta-globin domain by a mutation within the transgene. We propose that multiple, moveable Ig kappa sequences (that are normally located downstream of the transcription start site) cooperate to bring a hypermutation priming factor to the transcription initiation complex; a mutation domain is thereby created downstream of the promoter but the local sequence defines the detailed pattern of mutation within that domain.

Animals↗

Monitoring and interpreting the intrinsic features of somatic hypermutation.

We have used both normal and transgenic mice to analyse the recruitment and targeting of somatic hypermutation to the immunoglobulin loci. We compare methods for analysing hypermutation and discuss how large databases of mutations can be assembled by PCR amplification of the rearranged V-gene flanks from the germinal centre B cells of normal mice as well as by transgene-specific amplification from transgenic B cells. Such studies confirm that hypermutation is preferentially targeted to the immunoglobulin V gene with the bcl6 gene, for example, escaping this intense mutational targeting in germinal centre B cells. We review our data concerning the nature of the hypermutation domain and the targeting of hotspots within that domain. We consider how enhancer-mediated recruitment of hypermutation to the immunoglobulin loci operates in a clonally maintained fashion and illustrate how both the degree of expression and demethylation of the transgene broadly correlate with its mutability.

Animals↗

Rapid methods for the analysis of immunoglobulin gene hypermutation: application to transgenic and gene targeted mice.

Hypermutation of immunoglobulin genes is a key process in antibody diversification. Little is known about the mechanism, but the availability of rapid facile assays for monitoring immunoglobulin hypermutation would greatly aid the development of culture systems for hypermutating B cells as well as the screening for individuals deficient in the process. Here we describe two such assays. The first exploits the non-randomness of hypermutation. The existence of a mutational hotspot in the Ser31 codon of a transgenic immunoglobulin V gene allowed us to use PCR to detect transgene hypermutation and identify cell populations in which this mutation had occurred. For animals that do not carry immunoglobulin transgenes, we exploited the fact that hypermutation extends into the region flanking the 3'-side of the rearranged J segments. We show that PCR amplification of the 3'-flank of VDJH rearrangements that involve members of the abundantly-used VHJ558 family provides a large database of mutations where the germline counterpart is unequivocally known. This assay was particularly useful for analysing endogenous immunoglobulin gene hypermutation in several mouse strains. As a rapid assay for monitoring mutation in the JH flanking region, we show that one can exploit the fact that, following denaturation/renaturation, the PCR amplified JH flanking region DNA from germinal centre B cells yields mismatched heteroduplexes which can be quantified in a filter binding assay using the bacterial mismatch repair protein MutS -Wagner et al. (1995) Nucleic Acids Res. 23, 3944-3948-. Such assays enabled us, by example, to show that antibody hypermutation proceeds in the absence of the p53 tumour suppressor gene product.

Animals↗

Growth, development, and sexual dimorphism in vervet monkeys (Cercopithecus aethiops) at four sites in Kenya.

Body weight and ten body segment measurements were collected from 367 wild-trapped vervet monkeys (Cercopithecus aethiops) in central and southern Kenya. The animals represent between 70 and 95% of the animals in each of 30 troops at four geographical locations separated by 80 to 380 km. The capture sites differed in altitude, mean annual rainfall and temperature. Two questions are addressed: (1) what are the differences in male and female growth patterns, and (2) what is the relationship between size, climate, and availability of food? Each animal was assigned to an age class based on dental examination. Means for all variables do not diverge for males and females from birth to age class 4 (15-18 months). After this, male and female growth rates diverge. This sexual dimorphism in growth pattern may reflect timing of entry into the reproductive community. A nested analysis of variance (ANOVA) was employed to compare sites, groups within sites and individuals within groups. Statistically significant differences between sites in body weight and body segment measurements are found for adult females. Except for tail length, these differences do not follow Bergmann's or Allen's Rules correlating size differences and temperature, but rather may reflect proximity to cultivated areas or tourist lodges with greater access to human food.

Age Determination by Teeth↗

Specific transcription of the unrearranged TCR V beta 8.2 gene in lymphoid tissues occurs independently of V(D)J rearrangement.

A truncated T cell receptor (TCR) V beta 8.2 polypeptide expressed on the surface of a precursor lymphoid cell line and on a subset of mesenteric lymph node cells has previously been shown to be encoded by transcripts from unrearranged V beta 8 genes. Germline V beta 8 transcription has now been demonstrated in multiple lymphoid and non-lymphoid tissues in mice of varying ages and in cultured cell lines by reverse transcription-polymerase chain reaction (RT-PCR). Significant levels of V beta 8 germline transcription were found in thymus, spleen, liver and bone marrow and in all lymphoid cell lines studied. Germline V beta 8 transcription in the liver dropped as mice aged, and increased in the bone marrow. Germline V beta 8 transcription was also detectable in thymus, spleen, liver and bone marrow of RAG-1-/- mice. This indicated that it is not dependent upon the presence of mature lymphoid cells, nor necessarily related to V(D)J rearrangement events. Semi-quantitative polymerase chain reaction (PCR) and hybridization with oligonucleotides specific for V beta 8.1, 8.2 and 8.3 showed that the V beta 8.2 gene produced at least 90% of all the germline V beta 8 transcripts in all of the tissues examined. The significance of these results in lymphoid cell development and for models of the regulation of V(D)J rearrangement are discussed.

Alternative Splicing↗

GSP-1 genes are linked to the grain hardness locus (Ha) on wheat chromosome 5D.

An important determinant of wheat grain quality is the hardness of the grain. The trait is controlled by a major locus, Ha, on the short arm of chromosome 5D. Purified starch granules from soft-grained wheats have associated with them 15-kDa polypeptides called grain softness proteins (GSPs) or "friabilins." Genes that encode one family of closely related GSP polypeptides - GSP-1 genes - were mapped using chromosome substitution lines to the group 5 chromosomes. An F2 population segregating for hard and soft alleles at the Ha locus on a near-isogenic background was used in a single-seed study of the inheritance of grain softness and of GSP-1 alleles. Grain softness versus grain hardness was inherited in a 3:1 ratio. The presence versus absence of GSPs in single seed starch preparations was coinherited with grain softness versus hardness. This showed that grain softness is primarily determined by seed, and not by maternal, genotype. In addition, no recombination was detected in 44 F2 plants between GSP-1 restriction fragment length polymorphisms and Ha alleles. Differences between hard and soft wheat grains in membrane structure and lipid extractability have been described and, of the three characterized proteins that are part of the mixture of 15-kDa polypeptides called GSPs, at least two, and probably all three, are proteins that bind polar lipids. The data are interpreted to suggest that the Ha locus may encode one or more members of a large family of lipid-binding proteins.

Alleles↗

The targeting of somatic hypermutation.

Somatic hypermutation does not occur randomly within immunoglobulin V genes but, rather, is preferentially targeted to certain nucleotide positions (hot spots) and away from others (cold spots). Cold spots often coincide with residues essential for V gene folding. Hotspots, which appear to be strategically located to favour affinity maturation, are most frequently located in the CDRs (particularly CDR1) though conserved hotspots are also found at the base of FR3. Hotspots are in part created by local DNA sequence and the strong biases of codon usage in V genes indicate that the genes have evolved such that somatic hypermutation is targeted to those parts of the V where it is likely to prove most useful. These features of mutational hotspots and biased codon usage are also evident in V genes of lower animals suggesting that diversification by strategic targeting of non-templated mutation may have evolved early in antigen receptor evolution.

Animals↗

Germline transcription and expression of Tcrb-V8 genes in peripheral mouse lymphoid tissues.

Germline transcription of the Tcrb-V8.2 gene has been recently shown to occur in a lymphoid precursor cell line and to result in weak expression of an aberrant T-cell receptor (Tcr) beta chain on the cell surface. An investigation into the expression of a similar Tcr structure in normal lymphoid sites has involved antibody staining and sorting to identify a minor subset of Tcr-Vbeta+ Cbeta- cells in mesenteric lymph node and thymus. These cells have been analyzed by reverse transcriptase-polymerase chain reaction for the presence of transcripts encoded by bV8 genes in rearranged vs germline configuration in subsets of cells sorted on the basis of Tcrb-V8 and Tcrb-C gene expression. Germline transcripts were found in the Tcr-Vbeta- Cbeta- subset of cells in bone marrow, thymus, and mesenteric lymph node. They were also found to be present in the Tcr-Vbeta8(+) Cbeta+ subset of cells in thymus and mesenteric lymph node. Cells in the Tcr-Vbeta8(+) Cbeta- subset of mesenteric lymph node contained germline but no rearranged bV8 transcripts. The same thymus subset expressed high levels of both rearranged and germline bV8 transcripts. The presence of germline bV8 transcripts in Tcr-alphabeta- cells in bone marrow and mesenteric lymph node suggests that germline Tcrb-V8 gene transcription is unrelated to the differentiation of mature T cells. The possible function and significance of the expression of a truncated Tcr beta chain is discussed.

Animals↗