Search

Segmental duplications or low-copy repeats (LCRs) constitute approximately 5% of the sequenced portion of the human genome and are associated with many human congenital anomaly disorders. The low-copy repeats on chromosome 22q11.2 (LCR22s) mediate chromosomal rearrangements resulting in deletions, duplications and translocations. The evolutionary mechanisms leading to LCR22 formation is unknown. Four genes, USP18, BCR, GGTLA and GGT, map adjacent to the LCR22s and pseudogene copies are located within them. It has been hypothesized that gene duplication occurred during primate evolution, followed by recombination events, forming pseudogene copies. We investigated whether gene duplication could be detected in non-human hominoid species. FISH mapping was performed using probes to the four functional gene loci. There was evidence for a single copy in humans but additional copies in hominoid species. We then compared LCR22 copy number using LCR22 FISH probes. Lineage specific LCR22 variation was detected in the hominoid species supporting the hypothesis. To independently validate initial findings, real time PCR, and screening of gorilla BAC library filters were performed. This was compared to array comparative genome hybridization data available. The most striking finding was a dramatic amplification of LCR22s in the gorilla. The LCR22s localized to the telomeric or subtelomeric bands of gorilla chromosomes. The most parsimonious explanation is that the LCR22s became amplified by inter-chromosomal recombination between telomeric bands. In summary, our results are consistent with a lineage specific coupling between gene and LCR22 duplication events. The LCR22s thus serve as an important model for evolution of genome variation.

How populations diverge and give rise to distinct species remains a fundamental question in evolutionary biology, with important implications for a wide range of fields, from conservation genetics to human evolution. A promising approach is to estimate parameters of simple speciation models using polymorphism data from multiple loci. Existing methods, however, make a number of assumptions that severely limit their applicability, notably, no gene flow after the populations split and no intralocus recombination. To overcome these limitations, we developed a new Markov chain Monte Carlo method to estimate parameters of an isolation-migration model. The approach uses summaries of polymorphism data at multiple loci surveyed in a pair of diverging populations or closely related species and, importantly, allows for intralocus recombination. To illustrate its potential, we applied it to extensive polymorphism data from populations and species of apes, whose demographic histories are largely unknown. The isolation-migration model appears to provide a reasonable fit to the data. It suggests that the two chimpanzee species became reproductively isolated in allopatry approximately 850 Kya, while Western and Central chimpanzee populations split approximately 440 Kya but continued to exchange migrants. Similarly, Eastern and Western gorillas and Sumatran and Bornean orangutans appear to have experienced gene flow since their splits approximately 90 and over 250 Kya, respectively.

We devised a bioinformatics method for systematic identification of putative human-specific exon-deletion mutations that occurred after the divergence of human and chimpanzee and experimentally verified 2 of the predicted mutations in MOXD2 and S100A15A genes. MOXD2 gene encodes a monooxygenase that is highly conserved in mammals and is mostly expressed in the olfactory epithelium in mouse. The presence of a deletion of the last 2 exons and a polymorphic nonsense mutation in exon 6 suggests that MOXD2 gene is inactive in humans. S100A15A is a member of the S100 family of calcium-binding proteins, the mouse ortholog of which is expressed during epidermal maturation. Human S100A15A gene is likely to be inactive because the start codon-bearing exon is deleted in human. We propose that modification or inactivation of MOXD2 and S100A15A genes have contributed to the loss of certain smell sense in humans and to the development of human skin.

Dynamic gene repositioning has emerged as an additional level of epigenetic gene regulation. An early example was the report of a transient, spatial convergence (< or =2 microm) of oppositely imprinted regions ("kissing"), including the Angelman syndrome/Prader-Willi syndrome (AS/PWS) locus and the Beckwith-Wiedemann syndrome locus in human lymphocytes during late S phase. It was argued that kissing is required for maintaining opposite imprints in cycling cells. Employing 3D-FISH with a BAC contig covering the AS/PWS region, light optical, serial sectioning, and quantitative 3D-image analysis, we observed that both loci always retained a compact structure and did not form giant loops. Three-dimensional distances measured among various, homologous AS/PWS segments in 393 human lymphocytes, 132 human fibroblasts, and 129 lymphoblastoid cells from Gorilla gorilla revealed a wide range of distances at any stage of interphase and in G(0). At late S phase, 4% of nuclei showed distances < or =2 microm, 49% showed distances >6 microm, and 18% even showed distances >8 microm. A similar distance variability was found for Homo sapiens (HSA) 15 centromeres in a PWS patient with a deletion of the maternal AS/PWS locus and for the Beckwith-Wiedemann syndrome loci in human lymphocytes. A transient kiss during late S phase between loci widely separated at other stages of the cell cycle seems incompatible with known global constraints of chromatin movements in cycling cells. Further experiments suggest that the previously observed convergence of AS/PWS loci during late S phase was most likely a side effect of the convergence of nucleolus organizer region-bearing acrocentric human chromosomes, including HSA 15.

Female philopatry and male dispersal are the norm for most mammals, and females that remain in their natal region often derive foraging or social benefits from proximity to female kin. However, other factors, such as constraints on group size or a shortage of potential mates, may promote female dispersal even when female kin associations would be beneficial. In these cases, female kin associations might develop, not through female philopatry, but through female emigration to the same group. To date, little attention has been focused on the potential for kin-biased behaviour between females in female-dispersing species. Here we investigate the genetic relationships among adults in eight wild groups of unhabituated western gorillas (Gorilla gorilla) at the Mondika Research Center using microsatellite genotyping of DNA collected from hair and faeces. We found that almost half (40%) of adult females had an adult female relative in the same group and average within-group relatedness among females was significantly higher than that expected under a model of random dispersal. This provides the first genetic evidence that females can maintain social associations with female relatives in spite of routine natal and secondary dispersal. In addition, we show that females appear to avoid related silverback males when making dispersal decisions, suggesting that a strategy of non-random female dispersal may also function to avoid inbreeding.

Background: Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry., Methodology/principal Findings: Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages., Conclusions/significance: Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF.

Panels of BAC clones used in FISH experiments allow a detailed definition of chromosomal marker arrangement and orientation during evolution. This approach has disclosed the centromere repositioning phenomenon, consisting in the activation of a novel, fully functional centromere in an ectopic location, concomitant with the inactivation of the old centromere. In this study, appropriate panels of BAC clones were used to track the chromosome 11 evolutionary history in primates and nonprimate boreoeutherian mammals. Chromosome 11 synteny was found to be highly conserved in both primate and boreoeutherian mammalian ancestors. Amazingly, we detected four centromere repositioning events in primates (in Old World monkeys, in gibbons, in orangutans, and in the Homo-Pan-Gorilla (H-P-G) clade ancestor), and one in Equidae. Both H-P-G and Lar gibbon novel centromeres were flanked by large duplicons with high sequence similarity. Outgroup species analysis revealed that this duplicon was absent in phylogenetically more distant primates. The chromosome 11 ancestral centromere was probably located near the HSA11q telomere. The domain of this inactivated centromere, in humans, is almost devoid of segmental duplications. An inversion occurred in chromosome 11 in the common ancestor of H-P-G. A large duplicon, again absent in outgroup species, was found located adjacent to the inversion breakpoints. In Hominoidea, almost all the five largest duplicons of this chromosome appeared involved in significant evolutionary architectural changes.

We explored two hypotheses related to potential differences between sexes in dispersal behaviour in western lowland gorillas (Gorilla gorilla gorilla). Direct observations suggest that immature females have more opportunities to move between breeding groups than immature males. The distribution of kin dyadic relationships within and between groups does not, however, support this hypothesis. At larger geographical scales, dispersal is likely to be easier for males than females because of the solitary phase most blackbacks experience before founding their own breeding group. However, previous work indicates that males settle preferentially close to male kin. By specifically tracing female and male lineages with mitochondrial and Y-chromosomal genetic markers, we found that male gorillas in the 6000 km2 area we surveyed form a single population whereas females are restricted to the individual sites we sampled and do not freely move around this area. These differences are more correctly described as differences in dispersal distances, rather than differences in dispersal rates between sexes (both sexes emigrate from their natal group in this species). Differences in resource competition and dispersal costs between female and male gorillas are compatible with the observed pattern, but more work is needed to understand if these ultimate causes are responsible for sex-biased dispersal distances in western lowland gorillas.

Nuclear integrations of mitochondrial DNA (Numts) are widespread in many taxa and if left undetected can confound phylogeny interpretation and bias estimates of mitochondrial DNA (mtDNA) diversity. This is particularly true in gorillas, where recent studies suggest multiple integrations of the first hypervariable (HV1) domain of the mitochondrial control region. Problems can also arise through the inadvertent incorporation of artifacts produced by in vitro recombination between sequence types during polymerase chain reaction amplification. This issue has attracted little attention yet could potentially exacerbate errors in databases already contaminated by Numts. Using a set of existing diagnostic tools, this study set out to systematically inventory Numts and PCR recombinants in a gorilla HV1 sequence database and address the degree to which existing public databases are contaminated. Phylogenetic analysis revealed three distinct gorilla HV1 Numt groups (I, II, and III) that could be readily differentiated from mtDNA sequences by Numt-specific diagnostic sites and sequence-based motifs. Several instances of genuine recombination were also identified by a suite of detection methods. The location of putative breakpoints was identified by eye and by likelihood analysis. Findings from this study reveal widespread nuclear contamination of gorilla HV1 GenBank databases and underline the importance of recognizing not only Numts but also PCR recombinant artifacts as potential sources of data contamination. Guidelines for the routine identification of Numts and in vitro recombinants are presented and should prove useful in the detection of similar artifacts in other species mtDNA databases.

The long interspersed element-1 (LINE-1 or L1) is a highly successful retrotransposon in mammals. L1 elements have continued to actively propagate subsequent to the human-chimpanzee divergence, approximately 6 million years ago, resulting in species-specific inserts. Here, we report a detailed characterization of chimpanzee-specific L1 subfamily diversity and a comparison with their human-specific counterparts. Our results indicate that L1 elements have experienced different evolutionary fates in humans and chimpanzees within the past approximately 6 million years. Although the species-specific L1 copy numbers are on the same order in both species (1200-2000 copies), the number of retrotransposition-competent elements appears to be much higher in the human genome than in the chimpanzee genome. Also, while human L1 subfamilies belong to the same lineage, we identified two lineages of recently integrated L1 subfamilies in the chimpanzee genome. The two lineages seem to have coexisted for several million years, but only one shows evidence of expansion within the past three million years. These differential evolutionary paths may be the result of random variation, or the product of competition between L1 subfamily lineages. Our results suggest that the coexistence of several L1 subfamily lineages within a species may be resolved in a very short evolutionary period of time, perhaps in just a few million years. Therefore, the chimpanzee genome constitutes an excellent model in which to analyze the evolutionary dynamics of L1 retrotransposons.

Background: In order to obtain insights into the functionality of the human 4q35.2 domain harbouring the facioscapulohumeral muscular dystrophy (FSHD) locus, we investigated in African apes genomic and chromatin organisations, and the nuclear topology of orthologous regions., Results: A basic block consisting of short D4Z4 arrays (10-15 repeats), 4q35.2 specific sequences, and approximately 35 kb of interspersed repeats from different LINE subfamilies was repeated at least twice in the gorilla 4qter. This genomic organisation has undergone evolutionary remodelling, leading to the single representation of both the D4Z4 array and LINE block in chimpanzee, and the loss of the LINE block in humans. The genomic remodelling has had an impact on 4qter chromatin organisation, but not its interphase nuclear topology. In comparison with humans, African apes show very low or undetectable levels of FRG1 and FRG2 histone 4 acetylation and gene transcription, although histone deacetylase inhibition restores gene transcription to levels comparable with those of human cells, thus indicating that the 4qter region is capable of acquiring a more open chromatin structure. Conversely, as in humans, the 4qter region in African apes has a very peripheral nuclear localisation., Conclusion: The 4q subtelomere has undergone substantial genomic changes during evolution that have had an impact on chromatin condensation and the region's transcriptional regulation. Consequently, the 4qter genes in African apes and humans seem to be subjected to a different strategy of regulation in which LINE and D4Z4 sequences may play a pivotal role. However, the effect of peripheral nuclear anchoring of 4qter on these regulation mechanisms is still unclear. The observed differences in the regulation of 4qter gene expression between African apes and humans suggest that the human 4q35.2 locus has acquired a novel functional relevance.

Recent studies have suggested that gene gain and loss may contribute significantly to the divergence between humans and chimpanzees. Initial comparisons of the human and chimpanzee Y-chromosomes indicate that chimpanzees have a disproportionate loss of Y-chromosome genes, which may have implications for the adaptive evolution of sex-specific as well as reproductive traits, especially because one of the genes lost in chimpanzees is critically involved in spermatogenesis in humans. Here we have characterized Y-chromosome sequences in gorilla, bonobo, and several chimpanzee subspecies for 7 chimpanzee gene-disruptive mutations. Our analyses show that 6 of these gene-disruptive mutations predate chimpanzee-bonobo divergence at approximately 1.8 MYA, which indicates significant Y-chromosome change in the chimpanzee lineage relatively early in the evolutionary divergence of humans and chimpanzees.

It is well-accepted that studies of chromosomal changes which have occurred during the evolution of the great apes and the human provide clues towards the phylogeny of these species. Applying recently developed molecular cytogenetic approaches, this study on the chromosomes of the orangutan and the gorilla revealed the presence of cryptic, until now, unrecognized cytogenetic rearrangements mainly within the evolutionary dynamic subcentromeric and subtelomeric regions. On four orangutan chromosomes new rearrangements were detected such as a pericentric inversion in Pongo pygmaeus abeli (PPYa) #1, complex rearrangements on #2 of Pongo pygmaeus pygmaeus (PPYp) and PPYa and a subtelomeric deletion on PPYa&p #19. Additionally, the first centromere repositioning in the great apes was detected on PPYa&p #8. Moreover, the breakpoints of four pericentric inversions within the two orangutan subspecies and three pericentric inversions on Gorilla beringei beringei (GBEb) chromosomes #3, #11 and #13 were refined. The new molecular cytogenetic findings are discussed and compared with the available literature.

The genealogical relationship of human, chimpanzee, and gorilla varies along the genome. We develop a hidden Markov model (HMM) that incorporates this variation and relate the model parameters to population genetics quantities such as speciation times and ancestral population sizes. Our HMM is an analytically tractable approximation to the coalescent process with recombination, and in simulations we see no apparent bias in the HMM estimates. We apply the HMM to four autosomal contiguous human-chimp-gorilla-orangutan alignments comprising a total of 1.9 million base pairs. We find a very recent speciation time of human-chimp (4.1 +/- 0.4 million years), and fairly large ancestral effective population sizes (65,000 +/- 30,000 for the human-chimp ancestor and 45,000 +/- 10,000 for the human-chimp-gorilla ancestor). Furthermore, around 50% of the human genome coalesces with chimpanzee after speciation with gorilla. We also consider 250,000 base pairs of X-chromosome alignments and find an effective population size much smaller than 75% of the autosomal effective population sizes. Finally, we find that the rate of transitions between different genealogies correlates well with the region-wide present-day human recombination rate, but does not correlate with the fine-scale recombination rates and recombination hot spots, suggesting that the latter are evolutionarily transient., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Recently developed methods of individual-based analysis of genetic data allow an unprecedented opportunity to understand the relationships among fragmented populations. By defining population structure and identifying migrant individuals, such analyses can provide a framework to aid in evaluating the threats posed by inbreeding and reduced genetic variability as a consequence of limited gene flow among fragments. Here we investigate population structure in the critically endangered Cross River gorilla (Gorilla gorilla diehli) by applying a suite of individual-based analyses to data obtained from between one-quarter and one-third of the estimated total population through the use of noninvasively collected DNA samples. The population structure inferred using data from 11 autosomal microsatellite loci was broadly consistent with geography and habitat fragmentation, but showed no simple isolation-by-distance effects. In contrast to previous field surveys, which suggested that all gorilla localities were isolated from one another, we infer low levels of gene flow and identify migrants between habitat fragments as well as individuals of admixed ancestry, suggesting persistent recent reproductive contact between many of the localities. These results are encouraging for the conservation of the Cross River gorilla population. Conservation efforts should strive to maintain connectivity between subpopulations that are still in migratory contact and attempt to restore connectivity where it has been lost.

Relatively little is known about the evolutionary and demographic histories of gorillas, one of our closest living relatives. In this study, we used samples from both western (Gorilla gorilla) and eastern (Gorilla beringei) gorillas to infer the timing of the split between these geographically disjunct populations and to elaborate the demographic history of gorillas. Here we present DNA sequences from 16 noncoding autosomal loci from 15 western gorillas and 3 eastern gorillas, including 2 noninvasively sampled free-ranging individuals. We find that the genetic diversity of gorillas is similar to that of chimpanzees but almost twice as high as that of bonobos and humans. A significantly positive Fu & Li's D was observed for western gorillas, suggesting a complex demographic history with a constant, long-term population size and ancestral population structure. Among different population-split scenarios, our data suggest a complex history of western and eastern gorillas including an initial population split at around 0.9-1.6 MYA and subsequent, primarily male-mediated gene flow until approximately 80,000-200,000 years ago. Furthermore, simulations revealed that more gene flow took place from eastern to western gorilla populations than vice versa.

In order to investigate the replication timing properties of PCDH11X and PCDH11Y, a pair of protocadherin genes located in the hominid-specific non-pseudoautosomal homologous region Xq21.3/Yp11.2, we conducted a FISH-based comparative study in different human and non-human primate (Gorilla gorilla) cell types. The replication profiles of three genes from different regions of chromosome X (ZFX, XIST and ATRX) were used as terms of reference. Particular emphasis was given to the evaluation of allelic replication asynchrony in relation to the inactivation status of each gene. The human cell types analysed include neuronal cells and ICF syndrome cells, considered to be a model system for the study of X inactivation. PCDH11 appeared to be generally characterized by replication asynchrony in both male and female cells, and no significant differences were observed between human and gorilla, in which this gene lacks X-Y homologous status. However, in differentiated human neuroblastoma and cerebral cortical cells PCDH11X replication profile showed a significant shift towards allelic synchrony. Our data are relevant to the complex relationship between X-inactivation, as a chromosome-wide phenomenon, and asynchrony of replication and expression status of single genes on chromosome X.

Follicle-stimulating hormone (FSH) is essential for human reproduction. The unique functions of this hormone are provided by the FSH receptor-binding beta-subunit encoded by the FSHB gene. Resequencing and genotyping of FSHB in three European, two Asian and one African population, as well as in the great apes (chimpanzee, gorilla, orangutan), revealed low diversity and significant excess of polymorphisms with intermediate frequency alleles. Statistical tests for FSHB showed deviations from neutrality in all populations suggesting a possible effect of balancing selection. Two core haplotypes were identified (carried by 76-96.6% of each population's sample), the sequences of which are clearly separated from each other. As fertility most directly affects an organism's fitness, the carriers of these haplotypes have apparently had more success in human history to contribute to the next generation. There is a preliminary observation suggesting that the second most frequent FSHB haplotype may be associated with rapid conception success in females. Interestingly, the same haplotype is related to an ancestral FSHB variant shared with the ancestor of the great apes. The determination of the functional consequence of the two core FSHB variants may have implications for understanding and regulating human fertility, as well as in assisting infertility treatments.

We propose that select retropseudogenes of the high mobility group nonhistone chromosomal protein genes have recently integrated into mammalian genomes on the basis of the high sequence identity of the copies to the cDNA sequences derived from the original genes. These include the Hmg1 gene family in mice and the Hmgn2 family in humans. We investigated orthologous loci of several strains and species of Mus for presence or absence of apparently young Hmg1 retropseudogenes. Three of four analysed elements were specific to Mus musculus, two of which were not fixed, indicative of recent evolutionary origins. Additionally, we datamined a presumptive subfamily (Hmgz) of mouse Hmg1, but only identified one true element in the GenBank database, which is not consistent with a separate subfamily status. Two of four analysed Hmgn2 retropseudogenes were specific for the human genome, whereas a third was identified in human, chimpanzee and gorilla genomes, and a fourth additionally found in orangutan but absent in African green monkey. Flanking target-site duplications were consistent with LINE integration sites supporting LINE machinery for their mechanism of amplification. The human Hmgn2 retropseudogenes were full length, whereas the mouse Hmg1 elements were either full length or 3'-truncated at specific positions, most plausibly the result of use of alternative polyadenylation sites. The nature of their recent amplification success in relation to other retropseudogenes is unclear, although availability of a large number of transcripts during gametogenesis may be a reason. It is apparent that retropseudogenes continue to shape mammalian genomes, and may provide insight into the process of retrotransposition, as well as offer potential use as phylogenetic markers.

Noncoding regions are usually less subject to natural selection than coding regions and so may be more useful for studying human evolution. The recent surveys of worldwide DNA variation in four 10-kb noncoding regions revealed many interesting but also some incongruent patterns. Here we studied another 10-kb noncoding region, which is in 6p22. Sixty-six single-nucleotide polymorphisms were found among the 122 worldwide human sequences, resulting in 46 genotypes, from which 48 haplotypes were inferred. The distribution patterns of DNA variation, genotypes, and haplotypes suggest rapid population expansion in relatively recent times. The levels of polymorphism within human populations and divergence between humans and chimpanzees at this locus were generally similar to those for the other four noncoding regions. Fu and Li's tests rejected the neutrality assumption in the total sample and in the African sample but Tajima's test did not reject neutrality. A detailed examination of the contributions of various types of mutations to the parameters used in the neutrality tests clarified the discrepancy between these test results. The age estimates suggest a relatively young history in this region. Combining three autosomal noncoding regions, we estimated the long-term effective population size of humans to be 11,000 +/- 2800 using Tajima's estimator and 17,600 +/- 4700 using Watterson's estimator and the age of the most recent common ancestor to be 860,000 +/- 258,000 years ago.

Mammalian oxidative phosphorylation (OXPHOS) complexes I, III, IV and V are assembled from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) encoded subunits, with complex I encompassing 39 nDNA and seven mtDNA subunits. Yet the sequence variation of the mtDNA genes is more than ten fold greater than that of the nDNA encoded genes of the OXPHOS complexes and the mtDNA proteins have been found to be influenced by positive (adaptive) selection. To maintain a functional complex I, nDNA and mtDNA subunits must interact, implying that certain nDNA complex I genes may also have been influenced by positive selection. To determine if positive selection has influenced nDNA complex I genes, we analyzed the DNA sequences of all of the nDNA and mtDNA encoded complex I subunits from orangutan, gorilla, chimpanzee, human and all available vertebrate sequences. This revealed that three nDNA complex I genes (NDUFC2, NDUFA1, and NDUFA4) had significantly increased amino acid substitution rates by both PAML and Z-test, suggesting that they have been subjected to adaptive selection during primate radiation. Since all three of these subunits reside in the membrane domain of complex I along with the mtDNA subunits, we compared amino acid changes in these three nDNA genes with those of the mtDNA genes across species. Changes in the nDNA NDUFC2 cysteine 39 were found to correlate with those in the mtDNA ND5 cysteine 330. Therefore, adaptive selection has influenced some nDNA complex I genes and nDNA and mtDNA complex I genes may have co-evolved.

Background: Killer Immunoglobulin-like Receptors (KIR) are essential immuno-surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. Since few KIR remain orthologous between species, with only one of them, KIR2DL4, shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear., Results: Using comparative analyses, we have identified the ancestral KIR lineage (provisionally named KIR3DL0) in primates. We show KIR3DL0 to be highly conserved with the identification of orthologues in human (Homo sapiens), common chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), rhesus monkey (Macaca mulatta) and common marmoset (Callithrix jacchus). We predict KIR3DL0 to encode a functional molecule in all primates by demonstrating expression in human, chimpanzee and rhesus monkey. Using the rhesus monkey as a model, we further show the expression profile to be typical of KIR by quantitative measurement of KIR3DL0 from an enriched population of natural killer cells., Conclusion: One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. Based on genomic, cDNA, expression and phylogenetic data, we report a novel lineage of immunoglobulin receptors belonging to the KIR family, which is highly conserved throughout 50 million years of primate evolution.

In the present study we focus on the nucleotide and the inferred amino acid variation occurring in humans and other primate species for mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase, a gene recently supposed to contribute to cognitive performance in humans. We determined 2527 bp of coding, intronic, and flanking sequences from chimpanzee, bonobo, gorilla, orangutan, gibbon, and macaque. We also resequenced the entire coding sequence on 39 independent chromosomes from Italian families. Four variable coding sites were genotyped in additional populations from Europe, Africa, and Asia. A test for constancy of the nonsynonymous vs. synonymous rates of nucleotide changes revealed that primates are characterized by largely variable d(N)/d(S) ratios. On a background of strong conservation, probably controlled by selective constraints, the lineage leading to humans showed a ratio increased to 0.42. Human polymorphic levels fall in the range reported for other genes, with a pattern of frequency and haplotype structure strongly suggestive of nonneutrality. The comparison with the primate sequences allowed inferring the ancestral state at all variable positions, suggesting that the c.538(C) allele and the associated functional variant is indeed a derived state that is proceeding to fixation. The unexpected pattern of human polymorphism compared to interspecific findings outlines the possibility of a recent positive selection on some variants relevant to new cognitive capabilities unique to humans.

Bootstrap Analysis is a common tool in cladistics, and consequently many authors tend to believe that it could be close to a test of monophyly. In fact, it is only a procedure to calculate the redundancy of a certain character pattern among taxa. To demonstrate this, we set up a study with questionable data: Four skulls of great apes and humans were digitally photographed, and the pixels' brightness values were simply transformed to a one-zero-matrix, which was then used to calculate a Wagner tree with PHYLIP. As a rule, the higher the resolution of the photos is, the higher are the bootstrap values of supported taxa (and the lower are the bootstrap values of non-supported data). Redundancy of intertaxic information might indeed be an indicator of phylogenetic relationship, but can also be due to other reasons, like functional-adaptive needs in morphology, or semantic needs in a DNA-code. As a result, we tend to believe that high bootstrap values are actually less important than low ones. It is safer, based on a low bootstrap value, to claim that a certain taxon is not well supported by certain data. Therefore, we recommend discussions of low bootstrap values in future publications.

It was reported over 65 years ago that chimpanzees, like humans, vary in taste sensitivity to the bitter compound phenylthiocarbamide (PTC). This was suggested to be the result of a shared balanced polymorphism, defining the first, and now classic, example of the effects of balancing selection in great apes. In humans, variable PTC sensitivity is largely controlled by the segregation of two common alleles at the TAS2R38 locus, which encode receptor variants with different ligand affinities. Here we show that PTC taste sensitivity in chimpanzees is also controlled by two common alleles of TAS2R38; however, neither of these alleles is shared with humans. Instead, a mutation of the initiation codon results in the use of an alternative downstream start codon and production of a truncated receptor variant that fails to respond to PTC in vitro. Association testing of PTC sensitivity in a cohort of captive chimpanzees confirmed that chimpanzee TAS2R38 genotype accurately predicts taster status in vivo. Therefore, although Fisher et al.'s observations were accurate, their explanation was wrong. Humans and chimpanzees share variable taste sensitivity to bitter compounds mediated by PTC receptor variants, but the molecular basis of this variation has arisen twice, independently, in the two species.

cAMP-responsive element modulator (CREM) is a key transcription factor in the differentiation of round spermatids into mature spermatozoa. During spermiogenesis, CREM is regulated in part by activator of CREM in the testis (ACT), which activates CREM in a phosphorylation-independent fashion. We hypothesized that the ACT gene, which is expressed exclusively in the testis, could be involved in male factor infertility in patients with idiopathic-impaired spermatogenesis. To test this hypothesis, we sequenced the coding regions and flanking intronic regions of the ACT gene in 96 azoo- or oligospermic patients and 69 fertile controls. A total of 12 single-nucleotide polymorphisms (SNPs) was identified, and four of them leading to amino acid substitutions. An association study was performed based on calculated haplotype frequencies, and statistically significant differences were found between the patient and control populations for some haplotypes. To help establish the evolutionary relationships between the haplotypes, the coding regions of both the chimpanzee and the gorilla ACT gene were sequenced and evaluated. To test whether the different haplotypes conferred a functional change to the ACT protein, a yeast two-hybrid assay was designed to test the interaction between the two most divergent ACT haplotypes and their known binding partners, CREM and KIF17b. We identified one ACT haplotype that had a 45% reduction in its interaction with CREM. Our results suggest that different haplotypes within the ACT gene may contribute to male factor subfertility.

The one-male reproductive strategy implies that maturing males are temporarily excluded from reproduction. In gorillas, these excluded males live either solitarily or in nonbreeding groups (NBGs) that are devoid of adult females. The dynamics of NBGs are not well known. In this study, which was conducted on a gorilla population (Gorilla gorilla gorilla) of 377 individuals that visited the Lokoué clearing in the Republic of Congo, we detail how the NBGs formed, and analyze their dynamics according to age-sex classes, the relatedness of members, and the origin and destination of transferring individuals. We discuss the potential benefits gained by individuals living in these groups. The NBGs included mainly immature males, most of which appeared to have migrated voluntarily from their natal groups. Some individuals (including juvenile females) came from disbanded breeding groups (BGs). Migrants preferentially joined NBGs that included a silverback male. Their dispersal patterns were not determined by their degree of relatedness, but they tended to associate with related silverbacks. In this way, the migrants could enhance their protection against predators and gain experience with different environmental conditions. By tolerating and protecting offspring, aging silverbacks could enhance their inclusive fitness. Finally, young and healthy silverbacks could increase their likelihood of forming a future BG when unrelated females joined them.

Copy number differences (CNDs), and the concomitant differences in gene number, have contributed significantly to the genomic divergence between humans and other primates. To assess its relative importance, the genomes of human, common chimpanzee, bonobo, gorilla, orangutan and macaque were compared by comparative genomic hybridization using a high-resolution human BAC array (aCGH). In an attempt to avoid potential interference from frequent intra-species polymorphism, pooled DNA samples were used from each species. A total of 322 sites of large-scale inter-species CND were identified. Most CNDs were lineage-specific but frequencies differed considerably between the lineages; the highest CND frequency among hominoids was observed in gorilla. The conserved nature of the orangutan genome has already been noted by karyotypic studies and our findings suggest that this degree of conservation may extend to the sub-microscopic level. Of the 322 CND sites identified, 14 human lineage-specific gains were observed. Most of these human-specific copy number gains span regions previously identified as segmental duplications (SDs) and our study demonstrates that SDs are major sites of CND between the genomes of humans and other primates. Four of the human-specific CNDs detected by aCGH map close to the breakpoints of human-specific karyotypic changes [e.g., the human-specific inversion of chromosome 1 and the polymorphic inversion inv(2)(p11.2q13)], suggesting that human-specific duplications may have predisposed to chromosomal rearrangement. The association of human-specific copy number gains with chromosomal breakpoints emphasizes their potential importance in mediating karyotypic evolution as well as in promoting human genomic diversity.

Duplication of chromosomal segments and associated genes is thought to be a primary mechanism for generating evolutionary novelty. By comparative genome hybridization using a full-coverage (tiling) human BAC array with 79-kb resolution, we have identified 63 chromosomal segments, ranging in size from 0.65 to 1.3 Mb, that have inferred copy number increases in human relative to chimpanzee. These segments span 192 Ensembl genes, including 82 gene duplicates (41 reciprocal best BLAST matches). Synonymous and nonsynonymous substitution rates across these pairs provide evidence for general conservation of the amino acid sequence, consistent with the maintenance of function of both copies, and one case of putative positive selection for an uncharacterized gene. Surprisingly, the core histone genes H2A, H2B, H3, and H4 have been duplicated in the human lineage since our split with chimpanzee. The observation of increased copy number of a human cluster of core histone genes suggests that altered dosage, even of highly constrained genes, may be an important evolutionary mechanism.

Protocadherin X (PCDHX) and Protocadherin Y (PCDHY) are cell-surface adhesion molecules expressed predominantly in brain. The human PCDH11X/Y gene pair is located in the non-pseudoautosomal X-Y homologous region (Xq21.3/Yp11.2). The possible existence of PCDH11 gene dosage differences between human and non-human primates is of evolutionary significance with respect to species differences and escape from X inactivation, and has been repeatedly debated. Previous investigations on the X/Y homologous status of PCDH11 and adjacent sequences in non-human primates have highlighted the complexity of the molecular pattern and evolutionary history of this genomic region. This paper provides for the first time direct evidence for the absence of the PCDH11 genefrom the Y chromosome of chimpanzee (Pan troglodytes) as well as gorilla (Gorilla gorilla). By confirmingthe suspected lack of X-Y homologous status for PCDH11 in non-human primates, our results reinforce the hypothesis of a hominid-specific role for this gene in brain development., (Copyright (c) 2006 S. Karger AG, Basel.)

Fluorescence in situ hybridization (FISH) of human bacterial artificial chromosome (BAC) clones to orangutan metaphase spreads localized a breakpoint between human chromosome 3p25.1 and orangutan chromosome 2 to a <30-kb interval. The inversion occurred in a relatively gene-rich region with seven genes within 500 kb. The underlying breakpoint is closely juxtaposed to validated genes, however no functional gene has been disrupted by the evolutionary rearrangement. An approximately 21-kb DNA segment at the 3p25.1 breakpoint region has been duplicated intrachromosomally and interchromosomally to multiple regions in the orangutan and human genomes, providing additional evidence for the role of segmental duplications in hominoid chromosome evolution., (2006 S. Karger AG, Basel.)

Analyses of chromosomal rearrangements that have occurred during the evolution of the hominoids can reveal much about the mutational mechanisms underlying primate chromosome evolution. We characterized the breakpoints of the pericentric inversion of chimpanzee chromosome 18 (PTR XVI), which is homologous to human chromosome 16 (HSA 16). A conserved 23-kb inverted repeat composed of satellites, LINE and Alu elements was identified near the breakpoints and could have mediated the inversion by bringing the chromosomal arms into close proximity with each other, thereby facilitating intrachromosomal recombination. The exact positions of the breakpoints may then have been determined by local DNA sequence homologies between the inversion breakpoints, including a 22-base pair direct repeat. The similarly located pericentric inversion of gorilla (GGO) chromosome XVI, was studied by FISH and PCR analysis. The p- and q-arm breakpoints of the inversions in PTR XVI and GGO XVI were found to occur at slightly different locations, consistent with their independent origin. Further, FISH studies of the homologous chromosomal regions in macaque and orangutan revealed that the region represented by HSA BAC RP11-696P19, which spans the inversion breakpoint on HSA 16q11-12, was derived from the ancestral primate chromosome homologous to HSA 1. After the divergence of orangutan from the other great apes approximately 12 million years ago (Mya), a duplication of the corresponding region occurred followed by its interchromosomal transposition to the ancestral chromosome 16q. Thus, the most parsimonious interpretation is that the gorilla and chimpanzee homologs exhibit similar but nonidentical derived pericentric inversions, whereas HSA 16 represents the ancestral form among hominoids.

Allelic variation in codons that specify amino acids that line the peptide-binding pockets of HLA's Class II antigen-presenting proteins is superimposed on strikingly few deeply diverged haplotypes. These haplotypes appear to have been evolving almost independently for tens of millions of years. By complete resequencing of 20 haplotypes across the approximately 100-kbp region that spans the HLA-DQA1, -DQB1, and -DRB1 genes, we provide a detailed view of the way in which the genome structure at this locus has been shaped by the interplay of selection, gene-gene interaction, and recombination.

Methods for the identification of the sex and species of individuals from samples non-invasively taken from humans and gorillas were established. Amplification of a segment of amelogenin (AMG), which is an X-Y homologous gene, using two pairs of primers from human AMG, revealed both X- and Y-specific bands. The possibility of sex identification was examined by typing the AMG gene using hair and fecal samples from captive western lowland gorillas (Gorilla gorilla gorilla) in Japan and hair samples from wild eastern lowland gorillas (Gorilla beringei graueri) in the Kahuzi-Biega National Park, Democratic Republic of Congo, which were sexed by direct observation. Species-specific bands of AMG in gorillas and humans were identified by restriction fragment length polymorphisms analysis. These tests could be used for sexing unidentified individuals of wild western and eastern lowland gorillas, and screening contamination of human DNA from non-invasively acquired samples.

Retroviral infections of the germline have the potential to episodically alter gene function and genome structure during the course of evolution. Horizontal transmissions between species have been proposed, but little evidence exists for such events in the human/great ape lineage of evolution. Based on analysis of finished BAC chimpanzee genome sequence, we characterize a retroviral element (Pan troglodytes endogenous retrovirus 1 [PTERV1]) that has become integrated in the germline of African great ape and Old World monkey species but is absent from humans and Asian ape genomes. We unambiguously map 287 retroviral integration sites and determine that approximately 95.8% of the insertions occur at non-orthologous regions between closely related species. Phylogenetic analysis of the endogenous retrovirus reveals that the gorilla and chimpanzee elements share a monophyletic origin with a subset of the Old World monkey retroviral elements, but that the average sequence divergence exceeds neutral expectation for a strictly nuclear inherited DNA molecule. Within the chimpanzee, there is a significant integration bias against genes, with only 14 of these insertions mapping within intronic regions. Six out of ten of these genes, for which there are expression data, show significant differences in transcript expression between human and chimpanzee. Our data are consistent with a retroviral infection that bombarded the genomes of chimpanzees and gorillas independently and concurrently, 3-4 million years ago. We speculate on the potential impact of such recent events on the evolution of humans and great apes.

We report here protein sequences of fossil hominids, from two Neanderthals dating to approximately 75,000 years old from Shanidar Cave in Iraq. These sequences, the oldest reported fossil primate protein sequences, are of bone osteocalcin, which was extracted and sequenced by using MALDI-TOF/TOF mass spectrometry. Through a combination of direct sequencing and peptide mass mapping, we determined that Neanderthals have an osteocalcin amino acid sequence that is identical to that of modern humans. We also report complete osteocalcin sequences for chimpanzee (Pan troglodytes) and gorilla (Gorilla gorilla gorilla) and a partial sequence for orangutan (Pongo pygmaeus), all of which are previously unreported. We found that the osteocalcin sequences of Neanderthals, modern human, chimpanzee, and orangutan are unusual among mammals in that the ninth amino acid is proline (Pro-9), whereas most species have hydroxyproline (Hyp-9). Posttranslational hydroxylation of Pro-9 in osteocalcin by prolyl-4-hydroxylase requires adequate concentrations of vitamin C (l-ascorbic acid), molecular O(2), Fe(2+), and 2-oxoglutarate, and also depends on enzyme recognition of the target proline substrate consensus sequence Leu-Gly-Ala-Pro-9-Ala-Pro-Tyr occurring in most mammals. In five species with Pro-9-Val-10, hydroxylation is blocked, whereas in gorilla there is a mixture of Pro-9 and Hyp-9. We suggest that the absence of hydroxylation of Pro-9 in Pan, Pongo, and Homo may reflect response to a selective pressure related to a decline in vitamin C in the diet during omnivorous dietary adaptation, either independently or through the common ancestor of these species.

We present a detailed molecular evolutionary analysis of 1.2 Mb from the pericentromeric region of human 15q11. Sequence analysis indicates the region has been subject to extensive interchromosomal and intrachromosomal duplications during primate evolution. Comparative FISH analyses among non-human primates show remarkable quantitative and qualitative differences in the organization and duplication history of this region - including lineage-specific deletions and duplication expansions. Phylogenetic and comparative analyses reveal that the region is composed of at least 24 distinct segmental duplications or duplicons that have populated the pericentromeric regions of the human genome over the last 40 million years of human evolution. The value of combining both cytogenetic and experimental data in understanding the complex forces which have shaped these regions is discussed., (Copyright (c) 2005 S. Karger AG, Basel.)

In this paper an ancestral karyotype for primates, defining for the first time the ancestral chromosome morphology and the banding patterns, is proposed, and the ancestral syntenic chromosomal segments are identified in the human karyotype. The chromosomal bands that are boundaries of ancestral segments are identified. We have analyzed from data published in the literature 35 different primate species from 19 genera, using the order Scandentia, as well as other published mammalian species as out-groups, and propose an ancestral chromosome number of 2n = 54 for primates, which includes the following chromosomal forms: 1(a+c(1)), 1(b+c(2)), 2a, 2b, 3/21, 4, 5, 6, 7a, 7b, 8, 9, 10a, 10b, 11, 12a/22a, 12b/22b, 13, 14/15, 16a, 16b, 17, 18, 19a, 19b, 20 and X and Y. From this analysis, we have been able to point out the human chromosome bands more "prone" to breakage during the evolutionary pathways and/or pathology processes. We have observed that 89.09% of the human chromosome bands, which are boundaries for ancestral chromosome segments, contain common fragile sites and/or intrachromosomal telomeric-like sequences. A more in depth analysis of twelve different human chromosomes has allowed us to determine that 62.16% of the chromosomal bands implicated in inversions and 100% involved in fusions/fissions correspond to fragile sites, intrachromosomal telomeric-like sequences and/or bands significantly affected by X irradiation. In addition, 73% of the bands affected in pathological processes are co-localized in bands where fragile sites, intrachromosomal telomeric-like sequences, bands significantly affected by X irradiation and/or evolutionary chromosomal bands have been described. Our data also support the hypothesis that chromosomal breakages detected in pathological processes are not randomly distributed along the chromosomes, but rather concentrate in those important evolutionary chromosome bands which correspond to fragile sites and/or intrachromosomal telomeric-like sequences., (Copyright (c) 2005 S. Karger AG, Basel.)

The gene encoding claudin-1 (CLDN1) has been mapped to human chromosome 3 (HSA3; 3q28-->q29) using a radiation hybrid panel. Employing fluorescence in situ hybridization (FISH) we here show that a human P1-derived artificial chromosome (PAC) containing CLDN1 detects the orthologous sites in chromosomes of the great apes, chimpanzee, gorilla, and orangutan. Furthermore, the chromosomal position of CLDN1 was determined in mouse chromosomes by FISH. The position of fluorescent signals is confined to a single chromosomal site in both great apes and mouse and in each case maps to the chromosomal region that has conserved synteny with HSA3 (PTR2q28, GGO2q28, PPY2q38 and MMU16B1). Using a gene-specific probe our results are consistent with reports of the striking similarity of great ape and human genomes as illustrated previously by chromosome painting., (Copyright (c) 2005 S. Karger AG, Basel.)

Neurotrypsin is one of the extra-cellular serine proteases that are predominantly expressed in the brain and involved in neuronal development and function. Mutations in humans are associated with autosomal recessive non-syndromic mental retardation (MR). We studied the molecular evolution of neurotrypsin by sequencing the coding region of neurotrypsin in 11 representative non-human primate species covering great apes, lesser apes, Old World monkeys and New World monkeys. Our results demonstrated a strong functional constraint of neurotrypsin that was caused by strong purifying selection during primate evolution, an implication of an essential functional role of neurotrypsin in primate cognition. Further analysis indicated that the purifying selection was in fact acting on the SRCR domains of neurotrypsin, which mediate the binding activity of neurotrypsin to cell surface or extra-cellular proteins. In addition, by comparing primates with three other mammalian orders, we demonstrated that the absence of the first copy of the SRCR domain (exon 2 and 3) in mouse and rat was due to the deletion of this segment in the murine lineage., (Copyright 2005 S. Karger AG, Basel.)

Clones of a PAC contig encompassing the human AZFa region in Yq11.21 were comparatively FISH mapped to great ape Y chromosomes. While the orthologous AZFa locus in the chimpanzee, the bonobo and the gorilla maps to the long arm of their Y chromosomes in Yq12.1-->q12.2, Yq13.1-->q13.2 and Yq11.2, respectively, it is found on the short arm of the orang-utan subspecies of Borneo and Sumatra, in Yp12.3 and Yp13.2, respectively. Regarding the order of PAC clones and genes within the AZFa region, no differences could be detected between apes and man, indicating a strong evolutionary stability of this non-recombining region., (Copyright (c) 2005 S. Karger AG, Basel.)

The generation of panels of somatic cell hybrids specific for chimpanzee, gorilla, orangutan, and olive baboon is reported. The chromosome content of each hybrid clone was characterized using reverse painting on human normal metaphases and by the use of appropriate sequence tag sites (STSs), one for each chromosome arm. These resources can be advantageously exploited in the characterization of chromosome architecture of different primate species, with special reference to the discrimination of inter- and intra-chromosomal arrangement of segmental duplications., (Copyright (c) 2005 S. Karger AG, Basel.)

Chromosome rearrangement has been considered to be important in the evolutionary process. Here, we demonstrate the evolutionary relationship of the rearranged human chromosome 12 and the corresponding chromosome XII in apes (chimpanzee, bonobo, gorilla, orangutan, and gibbon) by examining PCR products derived from the breakpoints of inversions and by conducting shotgun sequencing of a gorilla fosmid clone containing the breakpoint and a "duplicated segment" (duplicon). We confirmed that a pair of 23-kb duplicons flank the breakpoints of inversions on the long and short arms of chimpanzee chromosome XII. Although only the 23-kb duplicon on the long arm of chimpanzee chromosome XII and its telomeric flanking sequence are found to be conserved among the hominoids (human, great apes, and gibbons), the duplicon on the short arm of chimpanzee chromosome XII is suggested to be the result of a duplication from that on the long arm. Furthermore, the shotgun sequencing of a gorilla fosmid indicated that the breakpoint on the long arm of the gorilla is located at a different position 1.9 kb from that of chimpanzee. The region is flanked by a sequence homologous to that of human chromosome 6q22. Our findings and sequence analysis suggest a close relationship between segmental duplication and chromosome rearrangement (or breakpoint of inversion) in Hominoidea. The role of the chromosome rearrangement in speciation is also discussed based on our new results., (Copyright (c) 2005 S. Karger AG, Basel.)

The strictly allopatric model of speciation makes definable predictions on the pattern of divergence, one of which is the uniformity in the divergence time across genomic regions. Using 345 coding and 143 intergenic sequences from the African great apes, we were able to reject the null hypothesis that the divergence time in the coding sequences (CDSs) and intergenic sequences (IGSs) is the same between human and chimpanzee. The conclusion is further supported by the analysis of whole-genome sequences between these species. The difference suggests a prolonged period of genetic exchange during the formation of these two species. Because the analysis should be generally applicable, collecting DNA sequence data from many genomic regions between closely related species should help to settle the debate over the prevalence of the allopatric mode of speciation.

Comparative FISH mapping of PAC clones covering almost 3 Mb of the human AZFa region in Yq11.21 to metaphases of human and great apes unravels breakpoints that were involved in species-specific Y chromosome evolution. An astonishing clustering of evolutionary breakpoints was detected in the very proximal region on the long arm of the human Y chromosome in Yq11.21. These breakpoints were involved in deletions, one specific for the human and another for the orang-utan Y chromosome, in a duplicative translocation/transposition specific for bonobo and chimpanzee Y chromosomes and in a pericentric inversion specific for the gorilla Y chromosome. In addition, our comparative results allow the deduction of a model for the human Y chromosome evolution., (Copyright (c) 2005 S. Karger AG, Basel.)

During this study, we analysed the pericentric inversion that distinguishes human chromosome 12 (HSA12) from the homologous chimpanzee chromosome (PTR10). Two large chimpanzee-specific duplications of 86 and 23 kb were observed in the breakpoint regions, which most probably occurred associated with the inversion. The inversion break in PTR10p caused the disruption of the SLCO1B3 gene in exon 11. However, the 86-kb duplication includes the functional SLCO1B3 locus, which is thus retained in the chimpanzee, although inverted to PTR10q. The second duplication spans 23 kb and does not contain expressed sequences. Eleven genes map to a region of about 1 Mb around the breakpoints. Six of these eleven genes are not among the differentially expressed genes as determined previously by comparing the human and chimpanzee transcriptome of fibroblast cell lines, blood leukocytes, liver and brain samples. These findings imply that the inversion did not cause major expression differences of these genes. Comparative FISH analysis with BACs spanning the inversion breakpoints in PTR on metaphase chromosomes of gorilla (GGO) confirmed that the pericentric inversion of the chromosome 12 homologs in GGO and PTR have distinct breakpoints and that humans retain the ancestral arrangement. These findings coincide with the trend observed in hominoid karyotype evolution that humans have a karyotype close to an ancestral one, while African great apes present with more derived chromosome arrangements., (Copyright (c) 2005 S. Karger AG, Basel.)

Two juvenile, male, captive-born lowland gorillas (Gorilla gorilla gorilla) with the same father but different mothers developed bilateral cataracts. The cataracts were surgically removed within 6 yr and 3 mo, respectively, of diagnosis, and foldable intraocular lenses were implanted. Although vision was not restored in one eye with a mature, 6-yr-old cataract in gorilla A, surgical intervention on the other eye was performed before a complete cataract developed, and vision was fully restored. Gorilla B was treated at the age of 17 mo, and normal visual development proceeded in both eyes. This animal developed bilateral after-cataract and therefore needed a second intervention in both eyes using Nd:YAG laser treatment. The genetic component of juvenile cataracts should be considered in breeding management programs.

In comparison to their close relatives the chimpanzees and humans, very little is known concerning the amount and structure of genetic variation in gorillas. Two species of gorillas are recognized and while the western gorillas number in the tens of thousands, only several hundred representatives of the mountain gorilla subspecies of eastern gorillas survive. To analyse the possible effects of these different population sizes, this study compares the variation observed at microsatellite and major histocompatibility complex (MHC) loci in samples of wild western and mountain gorillas, collected using a sampling scheme that targeted multiple social groups within defined geographical areas. Noninvasive samples proved a viable source of DNA for sequence analysis of the second exon of the DRB loci of the MHC. Observed levels of variation at the MHC locus were similar between the two gorilla species and were comparable to those in other primates. Comparison of results from analysis of variation at multiple microsatellite loci found only a slight reduction in heterozygosity for the mountain gorillas despite the relatively smaller population size.