Contrasting patterns of Y chromosome variation in Ashkenazi Jewish and host non-Jewish European populations

The molecular basis of more than 25 genetic diseases has been described in Ashkenazi Jewish populations. Most of these diseases are characterized by one or two major founder mutations that are present in the Ashkenazi population at elevated frequencies. One explanation for this preponderance of recessive diseases is accentuated genetic drift resulting from a series of dispersals to and within Europe, endogamy, and/or recent rapid population growth. However, a clear picture of the manner in which neutral genetic variation has been affected by such a demographic history has not yet emerged. We have examined a set of 32 binary markers (single nucleotide polymorphisms; SNPs) and 10 microsatellites on the non-recombining portion of the Y chromosome (NRY) to investigate the ways in which patterns of variation differ between Ashkenazi Jewish and their non-Jewish host populations in Europe. This set of SNPs defines a total of 20 NRY haplogroups in these populations, at least four of which are likely to have been part of the ancestral Ashkenazi gene pool in the Near East, and at least three of which may have introgressed to some degree into Ashkenazi populations after their dispersal to Europe. It is striking that whereas Ashkenazi populations are genetically more diverse at both the SNP and STR level compared with their European non-Jewish counterparts, they have greatly reduced within-haplogroup STR variability, especially in those founder haplogroups that migrated from the Near East. This contrasting pattern of diversity in Ashkenazi populations is evidence for a reduction in male effective population size, possibly resulting from a series of founder events and high rates of endogamy within Europe. This reduced effective population size may explain the high incidence of founder disease mutations despite overall high levels of NRY diversity.Electronic Supplementary Material Supplementary material is available in the online version of this article at D.M. Behar and D. Garrigan contributed equally to this workElectronic database information: URLs for the data in this article are as follows:ARLEQUIN,     

Response

It has been known for over a decade that a majority of men who self report as members of the Jewish priesthood (Cohanim) carry a characteristic Y chromosome haplotype termed the Cohen Modal Haplotype (CMH). The CMH has since been used to trace putative Jewish ancestral origins of various populations. However, the limited number of binary and STR Y chromosome markers used previously did not provide the phylogenetic resolution needed to infer the number of independent paternal lineages that are encompassed within the Cohanim or their coalescence times. Accordingly, we have genotyped 75 binary markers and 12 Y-STRs in a sample of 215 Cohanim from diverse Jewish communities, 1,575 Jewish men from across the range of the Jewish Diaspora, and 2,099 non-Jewish men from the Near East, Europe, Central Asia, and India. While Cohanim from diverse backgrounds carry a total of 21 Y chromosome haplogroups, 5 haplogroups account for 79.5% of Cohanim Y chromosomes. The most frequent Cohanim lineage (46.1%) is marked by the recently reported P58 T->C mutation, which is prevalent in the Near East. Based on genotypes at 12 Y-STRs, we identify an extended CMH on the J-P58* background that predominates in both Ashkenazi and non-Ashkenazi Cohanim and is remarkably absent in non-Jews. The estimated divergence time of this lineage based on 17 STRs is 3,190 ± 1,090 years. Notably, the second most frequent Cohanim lineage (J-M410*, 14.4%) contains an extended modal haplotype that is also limited to Ashkenazi and non-Ashkenazi Cohanim and is estimated to be 4.2 ± 1.3 ky old. These results support the hypothesis of a common origin of the CMH in the Near East well before the dispersion of the Jewish people into separate communities, and indicate that the majority of contemporary Jewish priests descend from a limited number of paternal lineages.     

What do we know about biological nitrogen fixation in insects? Evidence and implications for the insect and the ecosystem

Many insects feed on a low‐nitrogen diet, and the origin of their nitrogen supply is poorly understood. It has been hypothesized that some insects rely on nitrogen‐fixing bacteria (diazotrophs) to supplement their diets. Nitrogen fixation by diazotrophs has been extensively studied and convincingly demonstrated in termites, while evidence for the occurrence and role of nitrogen fixation in the diet of other insects is less conclusive. Here, we summarize the methods to detect nitrogen fixation in insects and review the available evidence for its occurrence (focusing on insects other than termites). We distinguish between three aspects of nitrogen fixation investigations: (i) detecting the presence of potential diazotrophs; (ii) detecting the activity of the nitrogen‐fixing enzyme; and (iii) detecting the assimilation of fixed nitrogen into the insect tissues. We show that although evidence from investigations of the first aspect reveals ample opportunities for interactions with potential diazotrophs in a variety of insects, demonstrations of actual biological nitrogen fixation and the assimilation of fixed nitrogen are restricted to very few insect groups, including wood‐feeding beetles, fruit flies, leafcutter ants, and a wood wasp. We then discuss potential implications for the insect's fitness and for the ecosystem as a whole. We suggest that combining these multiple approaches is crucial for the study of nitrogen fixation in insects, and argue that further demonstrations are desperately needed in order to determine the relative importance of diazotrophs for insect diet and fitness, as well as to evaluate their overall impact on the ecosystem.     

Population expansion in the North African Late Pleistocene signalled by mitochondrial DNA haplogroup U6

Background

Altruistic anti-predatory behaviours pose an evolutionary problem because they are costly to the actor and beneficial to the recipients. Altruistic behaviours can evolve through indirect fitness benefits when directed toward kin. The altruistic nature of anti-predatory behaviours is often difficult to establish because the actor can obtain direct fitness benefits, or the behaviour could result from selfish coercion by others, especially in eusocial animals. Non-eusocial parthenogenetically reproducing aphids form colonies of clone-mates, which are ideal to test the altruistic nature of anti-predatory defence behaviours. Many aphids release cornicle secretions when attacked by natural enemies such as parasitoids. These secretions contain an alarm pheromone that alerts neighbours (clone-mates) of danger, thereby providing indirect fitness benefits to the actor. However, contact with cornicle secretions also hampers an attacker and could provide direct fitness to the actor.

Results

We tested the hypothesis that cornicle secretions are altruistic by assessing direct and indirect fitness consequences of smearing cornicle secretions onto an attacker, and by manipulating the number of clone-mates that could benefit from the behaviour. We observed parasitoids, Aphidius rhopalosiphi, foraging singly in patches of the cereal aphid Sitobion avenae of varied patch size (2, 6, and 12 aphids). Aphids that smeared parasitoids did not benefit from a reduced probability of parasitism, or increase the parasitoids' handling time. Smeared parasitoids, however, spent proportionately more time grooming and less time foraging, which resulted in a decreased host-encounter and oviposition rate within the host patch. In addition, individual smearing rate increased with the number of clone-mates in the colony.

Conclusions

Cornicle secretions of aphids were altruistic against parasitoids, as they provided no direct fitness benefits to secretion-releasing individuals, only indirect fitness benefits through neighbouring clone-mates. Moreover, the use of cornicle secretions was consistent with their altruistic nature, because the occurrence of this behaviour increased with the size of indirect fitness benefits, the number of clone-mates that can benefit. This study provides evidence for a case of kin-directed altruistic defence outside eusocial animals.     

Does epigenetic polymorphism contribute to phenotypic variances in <Emphasis Type="Italic">Jatropha curcas</Emphasis> L.?

Background  

There is a growing interest in Jatropha curcas L. (jatropha) as a biodiesel feedstock plant. Variations in its morphology and seed productivity have been well documented. However, there is the lack of systematic comparative evaluation of distinct collections under same climate and agronomic practices. With the several reports on low genetic diversity in jatropha collections, there is uncertainty on genetic contribution to jatropha morphology.     

EspA Acts as a Critical Mediator of ESX1-Dependent Virulence in Mycobacterium tuberculosis by Affecting Bacterial Cell Wall Integrity

Mycobacterium tuberculosis (Mtb) requires the ESX1 specialized protein secretion system for virulence, for triggering cytosolic immune surveillance pathways, and for priming an optimal CD8+ T cell response. This suggests that ESX1 might act primarily by destabilizing the phagosomal membrane that surrounds the bacterium. However, identifying the primary function of the ESX1 system has been difficult because deletion of any substrate inhibits the secretion of all known substrates, thereby abolishing all ESX1 activity. Here we demonstrate that the ESX1 substrate EspA forms a disulfide bonded homodimer after secretion. By disrupting EspA disulfide bond formation, we have dissociated virulence from other known ESX1-mediated activities. Inhibition of EspA disulfide bond formation does not inhibit ESX1 secretion, ESX1-dependent stimulation of the cytosolic pattern receptors in the infected macrophage or the ability of Mtb to prime an adaptive immune response to ESX1 substrates. However, blocking EspA disulfide bond formation severely attenuates the ability of Mtb to survive and cause disease in mice. Strikingly, we show that inhibition of EspA disulfide bond formation also significantly compromises the stability of the mycobacterial cell wall, as does deletion of the ESX1 locus or individual components of the ESX1 system. Thus, we demonstrate that EspA is a major determinant of ESX1-mediated virulence independent of its function in ESX1 secretion. We propose that ESX1 and EspA play central roles in the virulence of Mtb in vivo because they alter the integrity of the mycobacterial cell wall.     

Deciphering the ancient and complex evolutionary history of human arylamine N-acetyltransferase genes

The human N-acetyltransferase genes NAT1 and NAT2 encode two phase-II enzymes that metabolize various drugs and carcinogens. Functional variability at these genes has been associated with adverse drug reactions and cancer susceptibility. Mutations in NAT2 leading to the so-called slow-acetylation phenotype reach high frequencies worldwide, which questions the significance of altered acetylation in human adaptation. To investigate the role of population history and natural selection in shaping NATs variation, we characterized genetic diversity through the resequencing and genotyping of NAT1, NAT2, and the pseudogene NATP in a collection of 13 different populations with distinct ethnic backgrounds and demographic pasts. This combined study design allowed us to define a detailed map of linkage disequilibrium of the NATs region as well as to perform a number of sequence-based neutrality tests and the long-range haplotype (LRH) test. Our data revealed distinctive patterns of variability for the two genes: the reduced diversity observed at NAT1 is consistent with the action of purifying selection, whereas NAT2 functional variation contributes to high levels of diversity. In addition, the LRH test identified a particular NAT2 haplotype (NAT2*5B) under recent positive selection in western/central Eurasians. This haplotype harbors the mutation 341T-->C and encodes the "slowest-acetylator" NAT2 enzyme, suggesting a general selective advantage for the slow-acetylator phenotype. Interestingly, the NAT2*5B haplotype, which seems to have conferred a selective advantage during the past approximately 6,500 years, exhibits today the strongest association with susceptibility to bladder cancer and adverse drug reactions. On the whole, the patterns observed for NAT2 well illustrate how geographically and temporally fluctuating xenobiotic environments may have influenced not only our genome variability but also our present-day susceptibility to disease.     

Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts

We investigated the effect of hypoxia on rat osteoblast function in long-term primary cultures. Reduction of pO2 from 20% to 5% and 2% decreased formation of mineralized bone nodules 1.7-fold and 11-fold, respectively. When pO2 was reduced further to 0.2%, bone nodule formation was almost abolished. The inhibitory effect of hypoxia on bone formation was partly due to decreased osteoblast proliferation, as measured by 3H-thymidine incorporation. Hypoxia also sharply reduced osteoblast alkaline phosphatase (ALP) activity and expression of mRNAs for ALP and osteocalcin, suggesting inhibition of differentiation to the osteogenic phenotype. Hypoxia did not increase the apoptosis of osteoblasts but induced a reversible state of quiescence. Transmission electron microscopy revealed that collagen fibrils deposited by osteoblasts cultured in 2% O2 were less organized and much less abundant than in 20% O2 cultures. Furthermore, collagen produced by hypoxic osteoblasts contained a lower percentage of hydroxylysine residues and exhibited an increased sensitivity to pepsin degradation. These data demonstrate the absolute oxygen requirement of osteoblasts for successful bone formation and emphasize the importance of the vasculature in maintaining bone health. We recently showed that hypoxia also acts in a reciprocal manner as a powerful stimulator of osteoclast formation. Considered together, our results help to explain the bone loss that occurs at the sites of fracture, tumors, inflammation and infection, and in individuals with vascular disease or anemia.