Reduced urine volume and changed renal sphingolipid metabolism in P2ry14-deficient mice.

The UDP-glucose receptor P2RY14, a rhodopsin-like G protein-coupled receptor (GPCR), was previously described as receptor expressed in A-intercalated cells of the mouse kidney. Additionally, we found P2RY14 is abundantly expressed in mouse renal collecting duct principal cells of the papilla and epithelial cells lining the renal papilla. To better understand its physiological function in kidney, we took advantage of a P2ry14 reporter and gene-deficient (KO) mouse strain. Morphometric studies showed that the receptor function contributes to kidney morphology. KO mice had a broader cortex relative to the total kidney area than wild-type (WT) mice. In contrast, the area of the outer stripe of the outer medulla was larger in WT compared to KO mice. Transcriptome comparison of the papilla region of WT and KO mice revealed differences in the gene expression of extracellular matrix proteins (e.g., decorin, fibulin-1, fibulin-7) and proteins involved in sphingolipid metabolism (e.g., small subunit b of the serine palmitoyltransferase) and other related GPCRs (e.g., GPR171). Using mass spectrometry, changes in the sphingolipid composition (e.g., chain length) were detected in the renal papilla of KO mice. At the functional level, we found that KO mice had a reduced urine volume but an unchanged glomerular filtration rate under normal chow and salt diets. Our study revealed P2ry14 as a functionally important GPCR in collecting duct principal cells and cells lining the renal papilla and the possible involvement of P2ry14 in nephroprotection by regulation of decorin.

Open housing drives the expression of immune response genes in the nasal mucosa, but not the olfactory bulb.

Nasal mucosa and olfactory bulb are separated by the cribriform plate which is perforated by olfactory nerves. We have previously demonstrated that the cribriform plate is permissive for T cells and monocytes and that viruses can enter the bulb upon intranasal injection by axonal transportation. Therefore, we hypothesized that nasal mucosa and olfactory bulb are equipped to deal with constant infectious threats. To detect genes involved in this process, we compared gene expression in nasal mucosa and bulb of mice kept under specific pathogen free (SPF) conditions to gene expression of mice kept on non-SPF conditions using RNA deep sequencing. We found massive alterations in the expression of immune-related genes of the nasal mucosa, while the bulb did not respond immunologically. The absence of induction of immune-related genes in the olfactory bulb suggests effective defence mechanisms hindering entrance of environmental pathogens beyond the outer arachnoid layer. The genes detected in this study may include candidates conferring susceptibility to meningitis.

Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences.

BACKGROUND: Comparisons of maternally-inherited mitochondrial DNA (mtDNA) and paternally-inherited non-recombining Y chromosome (NRY) variation have provided important insights into the impact of sex-biased processes (such as migration, residence pattern, and so on) on human genetic variation. However, such comparisons have been limited by the different molecular methods typically used to assay mtDNA and NRY variation (for example, sequencing hypervariable segments of the control region for mtDNA vs. genotyping SNPs and/or STR loci for the NRY). Here, we report a simple capture array method to enrich Illumina sequencing libraries for approximately 500 kb of NRY sequence, which we use to generate NRY sequences from 623 males from 51 populations in the CEPH Human Genome Diversity Panel (HGDP). We also obtained complete mtDNA genome sequences from the same individuals, allowing us to compare maternal and paternal histories free of any ascertainment bias. RESULTS: We identified 2,228 SNPs in the NRY sequences and 2,163 SNPs in the mtDNA sequences. Our results confirm the controversial assertion that genetic differences between human populations on a global scale are bigger for the NRY than for mtDNA, although the differences are not as large as previously suggested. More importantly, we find substantial regional variation in patterns of mtDNA versus NRY variation. Model-based simulations indicate very small ancestral effective population sizes (<100) for the out-of-Africa migration as well as for many human populations. We also find that the ratio of female effective population size to male effective population size (Nf/Nm) has been greater than one throughout the history of modern humans, and has recently increased due to faster growth in Nf than Nm. CONCLUSIONS: The NRY and mtDNA sequences provide new insights into the paternal and maternal histories of human populations, and the methods we introduce here should be widely applicable for further such studies.

Investigating the prehistory of Tungusic peoples of Siberia and the Amur-Ussuri region with complete mtDNA genome sequences and Y-chromosomal markers.

Evenks and Evens, Tungusic-speaking reindeer herders and hunter-gatherers, are spread over a wide area of northern Asia, whereas their linguistic relatives the Udegey, sedentary fishermen and hunter-gatherers, are settled to the south of the lower Amur River. The prehistory and relationships of these Tungusic peoples are as yet poorly investigated, especially with respect to their interactions with neighbouring populations. In this study, we analyse over 500 complete mtDNA genome sequences from nine different Evenk and even subgroups as well as their geographic neighbours from Siberia and their linguistic relatives the Udegey from the Amur-Ussuri region in order to investigate the prehistory of the Tungusic populations. These data are supplemented with analyses of Y-chromosomal haplogroups and STR haplotypes in the Evenks, Evens, and neighbouring Siberian populations. We demonstrate that whereas the North Tungusic Evenks and Evens show evidence of shared ancestry both in the maternal and in the paternal line, this signal has been attenuated by genetic drift and differential gene flow with neighbouring populations, with isolation by distance further shaping the maternal genepool of the Evens. The Udegey, in contrast, appear quite divergent from their linguistic relatives in the maternal line, with a mtDNA haplogroup composition characteristic of populations of the Amur-Ussuri region. Nevertheless, they show affinities with the Evenks, indicating that they might be the result of admixture between local Amur-Ussuri populations and Tungusic populations from the north.

Genetic perspectives on the origin of clicks in Bantu languages from southwestern Zambia.

Some Bantu languages spoken in southwestern Zambia and neighboring regions of Botswana, Namibia, and Angola are characterized by the presence of click consonants, whereas their closest linguistic relatives lack such clicks. As clicks are a typical feature not of the Bantu language family, but of Khoisan languages, it is highly probable that the Bantu languages in question borrowed the clicks from Khoisan languages. In this paper, we combine complete mitochondrial genome sequences from a representative sample of populations from the Western Province of Zambia speaking Bantu languages with and without clicks, with fine-scaled analyses of Y-chromosomal single nucleotide polymorphisms and short tandem repeats to investigate the prehistoric contact that led to this borrowing of click consonants. Our results reveal complex population-specific histories, with female-biased admixture from Khoisan-speaking groups associated with the incorporation of click sounds in one Bantu-speaking population, while concomitant levels of potential Khoisan admixture did not result in sound change in another. Furthermore, the lack of sequence sharing between the Bantu-speaking groups from southwestern Zambia investigated here and extant Khoisan populations provides an indication that there must have been genetic substructure in the Khoisan-speaking indigenous groups of southern Africa that did not survive until the present or has been substantially reduced.

A draft sequence of the Neandertal genome.

Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.