Estimation of the ancestral effective population sizes of African great apes under different selection regimes

Reliable estimates of ancestral effective population sizes are necessary to unveil the population-level phenomena that shaped the phylogeny and molecular evolution of the African great apes. Although several methods have previously been applied to infer ancestral effective population sizes, an analysis of the influence of the selective regime on the estimates of ancestral demography has not been thoroughly conducted. In this study, three independent data sets under different selective regimes were used were composed to tackle this issue. The results showed that selection had a significant impact on the estimates of ancestral effective population sizes of the African great apes. The inference of the ancestral demography of African great apes was affected by the selection regime. The effects, however, were not homogeneous along the ancestral populations of great apes. The effective population size of the ancestor of humans and chimpanzees was more impacted by the selection regime when compared to the same parameter in the ancestor of humans, chimpanzees and gorillas. Because the selection regime influenced the estimates of ancestral effective population size, it is reasonable to assume that a portion of the discrepancy found in previous studies that inferred the ancestral effective population size may be attributable to the differential action of selection on the genes sampled.     

Home-range characteristics and the influence of seasonality on female reproduction in white-handed gibbons (Hylobates lar) at Khao Yai National Park, Thailand

A three-year (2001-2003) study was carried out on the home range characteristics of seven wild white-handed gibbon (Hylobates lar) groups focusing on the spatio-temporal distribution of food resources at Khao Yai National Park in northeastern Thailand. These results were combined with 23 years (1980-2003) of reproductive performance data on seven females from the same focal groups. Reproductive performance was equal among females with regard to birth, weaning and maturation ratios, and independent of variation in food availability. Offspring mortality, however, was significantly positively correlated with home-range size. In addition, there was an increase in offspring mortality just after weaning, suggesting that the increase in the daily distance traveled by juveniles contributed to this mortality. Conceptions clustered during the first half of the year when food production was at its peak, which presumably allowed females to accumulate sufficient body reserves to resume ovarian cycling. Our results place Khao Yai gibbons closer to Cercopithecidae than great apes in terms of the temporal pattern of reproductive events, though gestation, lactation, inter-birth interval, and offspring maturation are considerably longer in gibbons, placing them closer to the other apes. Our findings underline the unique phylogenetic position of these small-bodied apes in terms of reproductive patterns in primates.     

From the ape's dilemma to the weanling's dilemma: early weaning and its evolutionary context

Although humans have a longer period of infant dependency than other hominoids, human infants, in natural fertility societies, are weaned far earlier than any of the great apes: chimps and orangutans wean, on average, at about 5 and 7.7 years, respectively, while humans wean, on average, at about 2.5 years. Assuming that living great apes demonstrate the ancestral weaning pattern, modern humans display a derived pattern that requires explanation, particularly since earlier weaning may result in significant hazards for a child. Clearly, if selection had favored the survival of the child, humans would wean later like other hominoids; selection, then, favored some trait other than the child's survival. It is argued here that our unique pattern of prolonged, early brain growth--the neurological basis for human intellectual ability--cannot be sustained much beyond one year by a human mother's milk alone, and thus early weaning, when accompanied by supplementation with more nutritious adult foods, is vital to the ontogeny of our larger brain, despite the associated dangers. Therefore, the child's intellectual development, rather than its survival, is the primary focus of selection. Consumption of more nutritious foods--derived from animal protein--increased by ca. 2.6 myr ago when a group of early hominins displayed two important behavioral shifts relative to ancestral forms: the recognition that a carcass represented a new and valuable food source-potentially larger than the usual hunted prey-and the use of stone tools to improve access to that food source. The shift in the hominin "prey image" to the carcass and the use of tools for butchery increased the amount of protein and calories available, irrespective of the local landscape. However, this shift brought hominins into competition with carnivores, increasing mortality among young adults and necessitating a number of social responses, such as alloparenting. The increased acquisition of meat ca. 2.6 Ma had significant effects on the later course of human evolution and may have initiated the origin of the genus Homo.     

Evolutionary transience of hypervariable minisatellites in man and the primates.

Using PCR, two minisatellite loci showing extreme repeat-unit copy-number variation in humans have been characterized in great apes and monkeys. In contrast to humans, minisatellite locus MS32 is monomorphic with only 3-4 diverged repeat units in great apes, Old World and New World monkeys, this organization presumably representing the relatively stable ancestral precursor state of the human hypervariable locus. Similarly, minisatellite MS1 shows extreme repeat-copy-number variability in man compared with low copy number and minimal variability in great apes. Analysis of variant repeat units shows that the 5' and 3' regions of MS1 are relatively stable in great apes and man, and that variability in man is confined to the central region of the minisatellite. In contrast to the great apes, MS1 is highly variable in Old World monkeys. These results, as well as computer simulations of minisatellite evolution based on known mutation rates, show that short minisatellites are stable within the genome, and that the degree of polymorphism at a given locus can change dramatically over a short period of evolutionary time. The ability of hypervariable minisatellites to detect highly informative loci by cross-species hybridization is therefore largely unpredictable.     

Natural selection on the olfactory receptor gene family in humans and chimpanzees

The olfactory receptor (OR) genes constitute the largest gene family in mammalian genomes. Humans have >1,000 OR genes, of which only ~40% have an intact coding region and are therefore putatively functional. In contrast, the fraction of intact OR genes in the genomes of the great apes is significantly greater (68%–72%), suggesting that selective pressures on the OR repertoire vary among these species. We have examined the evolutionary forces that shaped the OR gene family in humans and chimpanzees by resequencing 20 OR genes in 16 humans, 16 chimpanzees, and one orangutan. We compared the variation at the OR genes with that at intergenic regions. In both humans and chimpanzees, OR pseudogenes seem to evolve neutrally. In chimpanzees, patterns of variability are consistent with purifying selection acting on intact OR genes, whereas, in humans, there is suggestive evidence for positive selection acting on intact OR genes. These observations are likely due to differences in lifestyle, between humans and great apes, that have led to distinct sensory needs.     

Development of pancreatic enzymes in fetal and suckling rats with emphasis on lipase and colipase

Pancreatic amylase, chymotrypsinogen, lipase and colipase were assayed, at intervals, in rats from day 16 of fetal life until weaning. In the fetus, amylase and chymotrypsinogen accumulated regularly, in parallel, until birth. Lipase and colipase accumulation slowed down between day 20 and birth. The ratio of colipase to lipase was extremely high (9.5) and decreased until weaning towards adult values. Enzyme contents of the pancreas were depleted after birth and remained low until day 14. Intestinal concentrations were equally low, showing that pancreatic depletion was not due to hypersecretion. Protein synthesis was very active, intermediate between that of the fetus and of the adult. It is concluded that in the early suckling phase the proteins synthesized are mainly constitutive and not enzymatic. Starvation followed by refeeding showed that secretion sensitivity to nutritional stimulation only appears at 14 days. During the suckling period amylase concentrations decreased, evidencing a degree of nutritional sensitivity to the low level of carbohydrate in the diet. The productive capacity for lipase underwent a slow maturation which was not even complete at weaning, since concentrations had not yet reached adult level despite the high fat content of milk. This was in part compensated for by the high proportion of colipase but shows that lipase was not adaptative during this phase and that pancreatic lipase can hardly account for lipid digestion before weaning.     

Genetic basis of the trade-off between offspring number and quality in the bank vole

One of the main tenets of modern life-history theory is the negative relationship (trade-off) between the number and quality of offspring produced. Theory predicts a negative genetic correlation between these traits since both are closely related to fitness of individuals. However, the genetic basis of the trade-off has only been tested to a limited extent in natural populations. We examined whether size and quality of offspring are negatively related to litter size in the bank vole Clethrionomys glareolus. First, we found a significant negative phenotypic correlation between the number and size of offspring at birth in both laboratory and field populations of the bank vole. Second, a larger size at birth decreased the maturation age of female offspring in the laboratory, and increased the probability of breeding and the size of the first litter in the field. Furthermore, manipulation of offspring size at weaning indicated that structural effects of birth size in mammals have a more profound effect on the expression of life-history traits than weaning size. Finally, in addition to the phenotypic negative correlation between the number and size of offspring, we found evidence for a negative genetic correlation between these two traits, which confirms the genetic basis of the trade-off. This negative genetic covariation may have considerable effects on the rate and direction of evolution of the two related life-historical traits.     

The influence of the father on offspring development in the striped mouse

When males of a species follow different reproductive strategiesin different habitats, one might expect the strategy adoptedto maximize fitness payoffs under particular ecological conditions.Striped mice (Rhabdomys pumilio) males in the moist grasslandsof South Africa follow a roaming mating strategy, visiting severalreceptive females, and do not participate in parental care.In contrast, males in the arid succulent karoo are permanentmembers of social groups and help care for young. We predictedthat paternal care leads to fitness benefits in striped micefrom the succulent karoo but not from the grasslands. Experimentswere conducted simultaneously in both locations under captiveseminatural conditions to study offspring growth and survivalto weaning in two experimental groups: father absent and fatherpresent. In the succulent karoo, offspring development was fasterwhen the father was present, but the father's absence did notaffect offspring growth in the grasslands. The significantlylower night temperatures in the succulent karoo compared tothe grasslands negatively influenced offspring development duringthe first 3 days after birth, which in turn influenced offspringdevelopment until weaning. Exposure to low temperatures is energeticallycostly to free-living mice, as indicated by a greater loss ofbody weight during cold spring nights than warmer summer nights.We suggest that paternal care, particularly huddling of pups,improves offspring development in the succulent karoo, whereasthe presence or absence of the father does not appear to directlyinfluence offspring growth in the grasslands.     

Effects of maternal and grandmaternal flea infestation on offspring quality and quantity in a desert rodent: evidence for parasite-mediated transgenerational phenotypic plasticity

Parasites can cause a broad range of sublethal fitness effects across a wide variety of host taxa. However, a host’s efforts to compensate for possible parasite-induced fitness effects are less well-known. Parental effects may beneficially alter the offspring phenotype if parental environments sufficiently predict the offspring environment. Parasitism is a common stressor across generations; therefore, parental infestation could reliably predict the likelihood of infestation for offspring. However, little is known about relationships between parasitism and transgenerational phenotypic plasticity. Thus, we investigated how maternal and grandmaternal infestation with fleas (Xenopsylla ramesis) affected offspring quality and quantity in a desert rodent (Meriones crassus). We used a fully-crossed design with control and infested treatments to examine litter size, pup body mass at birth, and pup mass gain before weaning for combinations of maternal and grandmaternal infestation status. No effect of treatment on litter size or pup body mass at birth was found. However, maternal and grandmaternal infestation status significantly affected pre-weaning body mass gain, a proxy for the rate of maturation, in male pups. Pups gained significantly more weight before weaning if maternal and grandmaternal infestation statuses matched, regardless of the treatment. Thus, pups whose mothers and grandmothers experienced similar risks of parasitism, either both non-parasitized or both infested, would reach sexual maturity more quickly than those pups whose mothers’ infestation status did not match that of their grandmothers. These results support the contention that parents can receive external cues such as the risk of parasitism, that prompt them to alter offspring provisioning. Therefore, parasites could be a mediator of environmentally-induced maternal effects and could affect host reproductive fitness across multiple generations.     

Delayed motherhood decreases life expectancy of mouse offspring

This study analyzes the long-term effects of delayed motherhood on reproductive fitness and life expectancy of offspring in the mouse. Hybrid (C57BL/6JIco x CBA/JIco) first-generation (F1) females, either at the age of 10 or 51 wk, were individually housed with a randomly selected 12- to 14-wk-old hybrid male following a breeding pen system until females reached the end of their reproductive life. Reproductive fitness of second-generation (F2) females was tested from the age of 25 wk until the end of their reproductive life. In F2 males, the testing period ranged from the age of 52 wk until their natural death. Delayed motherhood of hybrid F1 female mice was associated with a decreased percentage of male F3 offspring at birth and lower life expectancy and body weight during adulthood of F2 offspring. There was, however, no evident negative effect of delayed motherhood on several reproductive fitness variables in either male or female F2 offspring. This included between-parturition interval, litter size at birth and at weaning, body weight at weaning and preweaning mortality of F3 pups, percentage of F3 litters with at least one pup cannibalized, and time at which female and male F2 offspring ceased their reproductive life. These data clearly show that delayed motherhood in the mouse is associated with negative long-term effects on offspring survival.     

Review: Maternal programming of development in the pig and the lactocrine hypothesis

Maternal effects on development are profound. Together, genetic and epigenetic maternal effects define the developmental trajectory of progeny and, ultimately, offspring phenotype. Maternally provisioned environmental conditions and signals affect conceptus, fetoplacental and postnatal development from the time of conception until weaning. In the pig, reproductive tract development is completed postnatally. Porcine uterine growth and uterine endometrial development occur in an ovary-independent manner between birth (postnatal day = PND 0) and PND 60. Milk-borne bioactive factors (MbFs), exemplified by relaxin, communicated from lactating dam to nursing offspring via a lactocrine mechanism, represent an important source of extraovarian uterotrophic support in the neonatal pig. Lactocrine deficiency from birth affects both the neonatal porcine uterine developmental program and trajectory of uterine development, with lasting consequences for endometrial function and uterine capacity in adult female pigs. The potential lactocrine signaling window extends from birth until the time of weaning. However, it is likely that the maternal lactocrine programming window – that period when MbFs communicated to nursing offspring have the greatest potential to affect critical organizational events in the neonate – encompasses a comparatively short period of time within 48 h of birth. Lactocrine deficiency from birth was associated with altered patterns of endometrial gene expression in neonatally lactocrine-deficient adult gilts during a critical period for conceptus–endometrial interaction on pregnancy day 13, and with reduced litter size, estimated at 1.4 pigs per litter, with no effect of parity. Data were interpreted to indicate that reproductive performance of female pigs that do not receive sufficient colostrum from birth is permanently impaired. Observations to date suggest that lactocrine-dependent maternal effects program postnatal development of the porcine uterus, endometrial functionality and uterine capacity. In this context, reproductive management strategies and husbandry guidelines should be refined to ensure that such practices promote environmental conditions that will optimize uterine capacity and fecundity. This will entail careful consideration of factors affecting lactation, the quality and abundance of colostrum/milk, and practices that will afford neonatal pigs with the opportunity to nurse and consume adequate amounts of colostrum.     

Impact of carnivory on human development and evolution revealed by a new unifying model of weaning in mammals

Our large brain, long life span and high fertility are key elements of human evolutionary success and are often thought to have evolved in interplay with tool use, carnivory and hunting. However, the specific impact of carnivory on human evolution, life history and development remains controversial. Here we show in quantitative terms that dietary profile is a key factor influencing time to weaning across a wide taxonomic range of mammals, including humans. In a model encompassing a total of 67 species and genera from 12 mammalian orders, adult brain mass and two dichotomous variables reflecting species differences regarding limb biomechanics and dietary profile, accounted for 75.5%, 10.3% and 3.4% of variance in time to weaning, respectively, together capturing 89.2% of total variance. Crucially, carnivory predicted the time point of early weaning in humans with remarkable precision, yielding a prediction error of less than 5% with a sample of forty-six human natural fertility societies as reference. Hence, carnivory appears to provide both a necessary and sufficient explanation as to why humans wean so much earlier than the great apes. While early weaning is regarded as essentially differentiating the genus Homo from the great apes, its timing seems to be determined by the same limited set of factors in humans as in mammals in general, despite some 90 million years of evolution. Our analysis emphasizes the high degree of similarity of relative time scales in mammalian development and life history across 67 genera from 12 mammalian orders and shows that the impact of carnivory on time to weaning in humans is quantifiable, and critical. Since early weaning yields shorter interbirth intervals and higher rates of reproduction, with profound effects on population dynamics, our findings highlight the emergence of carnivory as a process fundamentally determining human evolution.     

The cross-sectional geometry of the hand and foot bones of the hominoidea and its relationship to locomotor behavior

Cheiridia are valuable indicators of positional behavior, as they directly contact the substrate, but systematic comparison of the structural properties of both metacarpals and metatarsals has never been carried out. Differences in locomotor behavior among the great apes (knuckle-walking vs. quadrumanous climbing) can produce biomechanical differences that may be elucidated by the parallel study of cross-sectional characteristics of metacarpals and metatarsals. The aim of this work is to study the cross-sectional geometric properties of these bones and their correlation with locomotor behavior in large-bodied hominoids. The comparisons between bending moments of metacarpals and metatarsals of the same ray furnished interesting results. Metacarpals III and especially IV of the knuckle-walking African apes were relatively stronger than those of humans and orangutans, and metatarsal V of humans was relatively stronger than those of the great apes. Interestingly, the relative robusticity of the metacarpal IV of the quadrumanous orangutan was between that of the African apes and that of humans. The main conclusions of the study are: 1) cross-sectional dimensions of metacarpals and metatarsals are influenced by locomotor modes in great apes and humans; 2) interlimb comparisons of cross-sectional properties of metacarpals and metatarsals are good indicators of locomotor modes in great apes and humans; and 3) the results of this study are in accord with those of previous analyses of plantar pressure and morphofunctional traits of the same bones, and with behavioral studies. These results provide a data base from which it will be possible to compare the morphology of the fossils in order to gain insight into the locomotor repertoires of extinct taxa.     

A multigenerational effect of parental age on offspring size but not fitness in common duckweed (Lemna minor)

Classic theories on the evolution of senescence make the simplifying assumption that all offspring are of equal quality, so that demographic senescence only manifests through declining rates of survival or fecundity. However, there is now evidence that, in addition to declining rates of survival and fecundity, many organisms are subject to age‐related declines in the quality of offspring produced (i.e. parental age effects). Recent modelling approaches allow for the incorporation of parental age effects into classic demographic analyses, assuming that such effects are limited to a single generation. Does this ‘single‐generation’ assumption hold? To find out, we conducted a laboratory study with the aquatic plant Lemna minor, a species for which parental age effects have been demonstrated previously. We compared the size and fitness of 423 laboratory‐cultured plants (asexually derived ramets) representing various birth orders, and ancestral ‘birth‐order genealogies’. We found that offspring size and fitness both declined with increasing ‘immediate’ birth order (i.e. birth order with respect to the immediate parent), but only offspring size was affected by ancestral birth order. Thus, the assumption that parental age effects on offspring fitness are limited to a single generation does in fact hold for L. minor. This result will guide theorists aiming to refine and generalize modelling approaches that incorporate parental age effects into evolutionary theory on senescence.     

Pattern of maternal serum corticotropin-releasing hormone concentration during pregnancy in the common marmoset (Callithrix jacchus)

Corticotropin-releasing hormone (CRH), a potent neuropeptide, is produced by the placenta of anthropoid primates. No other mammals, including prosimian primates, are known to produce placental CRH. In humans, placental CRH appears to play an important role in the progression of pregnancy to parturition. Maternal circulating CRH begins to rise early in pregnancy and increases until parturition. Gorillas and chimpanzees share this pattern of increasing maternal CRH during pregnancy with humans. In humans, chimpanzees, and gorillas, maternal CRH and estradiol concentrations are correlated, consistent with the hypothesis that CRH is involved in the biosynthetic pathway for placental estrogen production. In contrast, in baboons, maternal circulating CRH rises precipitously early in pregnancy and then declines, though CRH is detectable until birth. This research was designed to investigate the pattern of maternal circulating CRH in the common marmoset during pregnancy. Blood samples were taken across gestation from nine subjects over 11 pregnancies, and the plasma was assayed for CRH. The pattern of maternal circulating CRH in the common marmoset was similar to that of the baboon, with a rapid rise starting at about 50 days postconception and a peak at approximately 70 days postconception. By 110 days postconception, CRH concentration had plateaued at a significantly lower value. The peak and mean values for CRH were associated with fetal number (e.g., females gestating triplets had higher values than females gestating twins). Urinary estradiol showed no association with plasma CRH concentration. Marmosets appear to differ from the great apes in this regard, and to share a pattern of maternal CRH during pregnancy with the baboon, indicating that the baboon and marmoset pattern may be ancestral. The function of the early rapid rise of CRH in baboons and marmosets, and the significance of this difference between monkeys and apes, are not known.     

Effect of the Japanese diet during pregnancy and lactation or post-weaning on the risk of metabolic syndrome in offspring

We examined the effects on offspring of ingestion of the 1975 Japanese diet during pregnancy and lactation and after weaning in mice. Pregnant dams were divided into groups that were fed the Japanese diet or a control diet and raised until offspring were weaned. The offspring after weaning were further divided into groups that were raised on the Japanese diet or the control diet. Ingestion of the Japanese diet after weaning suppressed accumulation of visceral fat in offspring, and reduced the amount of lipids in serum and liver. This effect was weakened if the Japanese diet was only ingested during pregnancy and lactation. Therefore, it was suggested that ingestion of the Japanese diet of mothers during pregnancy and lactation weakens the lipid accumulation inhibitory effect of the Japanese diet in children.     

Effects of feed restriction during pregnancy on maternal reproductive outcome,foetal hepatic IGF gene expression and offspring performance in the rabbit

Primiparous female rabbits have high nutritional requirements and, while it is recommended that they are subjected to an extensive reproductive rhythm, this could lead to overweight, affecting reproductive outcomes. We hypothesised that restricting food intake during the less energetic period of gestation could improve reproductive outcome without impairing offspring viability. This study compares two groups of primiparous rabbit does in an extensive reproductive programme, one in which feed was restricted from Day 0 to Day 21 of gestation (R021), and another in which does were fed ad libitum (control) throughout pregnancy. The mother and offspring variables compared were (1) mother reproductive outcomes at the time points pre-implantation (Day 3 postartificial insemination [AI]), preterm (Day 28 post-AI) and birth; and (2) the prenatal offspring characteristic IGF system gene expression in foetal liver, liver fibrosis and foetus sex ratio, and postnatal factor viability and growth at birth, and survival and growth until weaning. Feed restriction did not affect the conception rate, embryo survival, or the number of morulae and blastocysts recovered at Day 3 post-AI. Preterm placenta size and efficiency were similar in the two groups. However, both implantation rate (P < 0.001) and the number of foetuses (P = 0.05) were higher in the R021 mothers than controls, while there was no difference in foetal viability. Foetal size and weight, the weights of most organs, organ weight/BW ratios and sex ratio were unaffected by feed restriction; these variables were only affected by uterine position (P < 0.05). Conversely, in the R021 does, foetal liver IGBP1 and IGF2 gene expression were dysregulated despite no liver fibrosis and a normal liver structure. No effects of restricted feed intake were produced on maternal fertility, prolificacy, or offspring birth weight, but control females weaned more kits. Litter weight and mortality rate during the lactation period were also unaffected. In conclusion, pre-implantation events and foetal development were unaffected by feed restriction. While some genes of the foetal hepatic IGF system were dysregulated during pregnancy, liver morphology appeared normal, and the growth of foetuses and kits until weaning was unmodified. This strategy of feed restriction in extensive reproductive rhythms seems to have no significant adverse effects on dam reproductive outcome or offspring growth and viability until weaning.     

Is Mating Alone Enough to Inhibit Infanticide in Male Bank Voles?

Infanticide, the killing of conspecific young, is commonly recognized as an adaptive behavioural strategy enhancing the fitness of the perpetrator. Infanticide is supposed to be inhibited in several male rodent species after mating with a time lag to the time when perpetrators own offspring would be born. This is because males with no parental care do not recognize their own offspring. It has been suggested that copulation alone is enough to inhibit infanticidal behaviour in male rodents. Infanticidal behaviour occurs in more than 50% of male bank voles (Myodes glareolus), and offspring loss because of infanticide may have a great effect on breeding success and population recruitment. In a laboratory experiment, we studied whether infanticidal male bank voles after successful mating stop the killing of pups. Infanticidal males were paired with a female until successful copulation. After the young were born, the males’ infanticidal behaviour was studied from the time of expected birth of own pups until their post‐weaning age. We predicted that mated infanticidal males are inhibited from committing infanticide especially during the time period when pups are less than 10 d old. Against our prediction, 67% of the infanticidal males continued the killing of pups in the age of 3 d. Infanticidal behaviour remained stable, and half of the males were infanticidal still at the age of weaning of pups. Our results are contradictory to previous studies, as we observed no inhibition of infanticide during early life of pups nor increase in infanticide again when their own offspring would have reached the ‘safe’ age and size after weaning. We suggest that mating alone is not sufficient to inhibit infanticide. Thus, we suggest that other cues of the female with whom the male mated with or on her territory are needed for inhibition to occur.     

Inversion, duplication, and changes in gene context are associated with human chromosome 18 evolution

Human chromosome 18 differs from its homologues in the great apes by a pericentric inversion. We have identified a chimpanzee bacterial artificial chromosome that spans a region where a break is likely to have occurred in a human progenitor and have characterized the corresponding regions in both chimpanzees and humans. Interspecies sequence comparisons indicate that the ancestral break occurred between the genes ROCK1 and USP14. In humans, the inversion places ROCK1 near centromeric heterochromatin and USP14 adjacent to highly repetitive subtelomeric repeats. In addition, we provide evidence for a human segmental duplication that may have provided a mechanism for the inversion.