- TelNet - a database for human and yeast genes involved in telomere maintenance. [Journal Article]
- BGBMC Genet 2018 May 18; 19(1):32
- CONCLUSIONS: TelNet supports the annotation of genes identified from bioinformatics analysis pipelines to reveal possible connections with TM networks. We anticipate that TelNet will be a helpful resource for researchers that study telomeres.
- Genome-wide detection of selection signatures in Chinese indigenous Laiwu pigs revealed candidate genes regulating fat deposition in muscle. [Journal Article]
- BGBMC Genet 2018 May 18; 19(1):31
- CONCLUSIONS: Our results identified a number of regions showing signatures of selection, as well as a list of functionally candidate genes with potential effect on phenotypic traits, especially fat deposition in muscle. Our findings provide insights into the mechanisms of artificial selection of fat deposition and further facilitate follow-up functional studies.
- Establishment of Locally Adapted Mutations Under Divergent Selection. [Journal Article]
- GGenetics 2018 May 17
- We study the establishment probabilities of locally adapted mutations using a multi-type branching process framework. We find a surprisingly simple and intuitive analytical approximation for the esta...
We study the establishment probabilities of locally adapted mutations using a multi-type branching process framework. We find a surprisingly simple and intuitive analytical approximation for the establishment probabilities in a symmetric two-deme model under the assumption of weak (positive) selection. This is the first analytical closed-form approximation for arbitrary migration rate to appear in the literature. We find that the establishment probability lies between the weak and the strong migration limits if we condition the origin of the mutation to the deme where it is advantageous. This is not the case when we condition the mutation to first occur in a deme where it is disadvantageous. In this case we find that an intermediate migration rate maximizes the probability of establishment. We extend our results to the cases of multiple demes, two demes with asymmetric rates of gene flow, and asymmetric carrying capacities. The latter case allows us to illustrate how density regulation can affect establishment probabilities. Finally we use our results to investigate the role of gene flow on the rate of local adaptation and identify cases in which intermediate amounts of gene flow facilitate the rate of local adaptation as compared to two populations without gene flow.
- Serrate-Notch Signaling Regulates the Size of the Progenitor Cell Pool in Drosophila Imaginal Rings. [Journal Article]
- GGenetics 2018 May 17
- Drosophila imaginal rings are larval tissues composed of progenitor cells that are essential for the formation of adult foreguts, hindguts and salivary glands. Specified from subsets of ectoderm in t...
Drosophila imaginal rings are larval tissues composed of progenitor cells that are essential for the formation of adult foreguts, hindguts and salivary glands. Specified from subsets of ectoderm in the embryo, imaginal ring cells are kept quiescent until mid-second larval instar, and undergo rapid proliferation during the third instar to attain adequate numbers of cells that will replace apoptotic larval tissues for adult organ formation. Here we show that Notch signaling is activated in all three imaginal rings from middle embryonic stage to early pupal stage and that Notch signaling positively controls cell proliferation in all three imaginal rings during the third larval instar. Our mutant clonal analysis, knockdown and gain-of-function studies indicate that canonical Notch pathway components are involved in regulating the proliferation of these progenitor cells. Both trans-activation and cis-inhibition between the ligand and receptor control Notch activation in the imaginal ring. Serrate (Ser) is the ligand provided from neighboring imaginal ring cells that trans-activates Notch signaling, whereas both Ser and Delta (Dl) could cis-inhibit Notch activity when the ligand and the receptor are in the same cell. In addition, we show that Notch signaling expressed in middle embryonic and first larval stages is required for the initial size of imaginal rings. Taken together, these findings indicate that imaginal rings are excellent in vivo models to decipher how progenitor cell number and proliferation are developmentally regulated and that Notch signaling in these imaginal tissues is the primary growth-promoting signal that controls the size of the progenitor cell pool.
- Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations. [Journal Article]
- GGenetics 2018 May 16
- Ampliconic genes are multicopy, in majority found on sex-chromosomes and enriched for testis-expressed genes. While ampliconic genes have been associated with the emergence of hybrid incompatibilitie...
Ampliconic genes are multicopy, in majority found on sex-chromosomes and enriched for testis-expressed genes. While ampliconic genes have been associated with the emergence of hybrid incompatibilities, we know little about their copy number distribution and their turnover in human populations. Here we explore the evolution of human X- and Y-linked ampliconic genes by investigating copy number variation (CNV) and coding variation between populations using the Simons Genome Diversity Project. We develop a method to assess CNVs using the read-depth on modified X and Y chromosome targets containing only one repetition of each ampliconic gene. Our results reveal extensive standing variation in copy number both within and between human populations for several ampliconic genes. For the Y chromosome, we can infer multiple independent amplifications and losses of these gene copies even within closely related Y haplogroups, that diversified less than 50,000 years ago. Moreover, X and Y-linked ampliconic genes seem to have a faster amplification dynamic than autosomal multicopy genes. Looking at expression data from another study, we also find that XY-linked ampliconic genes with extensive copy number variation are significantly more expressed than genes with no copy number variation during meiotic sex-chromosome inactivation (for both X and Y) and post-meiotic sex chromosome repression (for the Y only). While we cannot rule out that the X-Y ampliconic genes are evolving neutrally, this study gives insights on the distribution of copy number within human populations, and demonstrates an extremely fast turnover in copy number of these regions.
- Hermes Transposon Mutagenesis Shows [URE3] Prion Pathology Prevented by a Ubiquitin-Targeting Protein: Evidence for Carbon/Nitrogen Assimilation Cross-Talk and a Second Function for Ure2p in Saccharomyces cerevisiae. [Journal Article]
- GGenetics 2018 May 16
- [URE3] is an amyloid-based prion of Ure2p, a regulator of nitrogen catabolism. While most variants of the [URE3] prion are toxic, mild variants that only slightly slow growth are more widely studied....
[URE3] is an amyloid-based prion of Ure2p, a regulator of nitrogen catabolism. While most variants of the [URE3] prion are toxic, mild variants that only slightly slow growth are more widely studied. The existence of several anti-prion systems suggests that some components may be protecting cells from potential detrimental effects of mild [URE3] variants. Our extensive Hermes transposon mutagenesis showed that disruption of YLR352W dramatically slows growth of [URE3-1] strains. Ylr352wp is an F-box protein, directing selection of substrates for ubiquitination by a cullin-containing E-3 ligase. For efficient ubiquitylation, cullin-dependent E3 ubiquitin ligases must be NEDDylated, modified by a ubiquitin-related peptide called NEDD8 (Rub1p in yeast). Indeed, we find that disruption of NEDDylation-related genes, RUB1, ULA1, UBA3 and UBC12 is also counterselected in our screen. We find that like ylr352wΔ [URE3] strains, ylr352wΔ ure2Δ strains do not grow on non-fermentable carbon sources. Overexpression of Hap4p, a transcription factor stimulating expression of mitochondrial proteins, or mutation of GLN1, encoding glutamine synthetase, allow growth of ylr352wΔ [URE3] strains on glycerol media. Supplying proline as a nitrogen source shuts off the nitrogen catabolite repression (NCR) function of Ure2p, but does not slow growth of ylr352wΔ strains, suggesting a distinct function of Ure2p in carbon catabolism. Also, gln1 mutations impair NCR, but actually relieve the growth defect of ylr352wΔ [URE3] and ylr352wΔ ure2Δ strains, again showing that loss of NCR is not producing the growth defect and suggesting Ure2p has another function. YLR352W largely protects cells from the deleterious effects of otherwise mild [URE3] variants, or of a ure2 mutation (the latter a rarer event), and we name it LUG1 (lets [URE3]/ure2 grow).
- Inferring the Probability of the Derived versus the Ancestral Allelic State at a Polymorphic Site. [Journal Article]
- GGenetics 2018 May 16
- It is known that the allele ancestral to the variation at a polymorphic site cannot be assigned with certainty, and that the most frequently used method to assign the ancestral state - maximum parsim...
It is known that the allele ancestral to the variation at a polymorphic site cannot be assigned with certainty, and that the most frequently used method to assign the ancestral state - maximum parsimony - is prone to misinference. Estimates of counts of sites that have a certain number of copies of the derived allele in a sample (the unfolded site frequency spectrum, uSFS) made by parsimony are therefore also biased. We previously developed a maximum likelihood method to estimate the uSFS for a focal species using information from two outgroups while assuming simple models of nucleotide substitution. Here, we extend this approach to allow multiple outgroups (implemented for three outgroups), potentially any phylogenetic tree topology and more complex models of nucleotide substitution. We find, however, that two outgroups and the Kimura 2-parameter model are adequate for uSFS inference in most cases. We show that using parsimony to infer the ancestral state at a specific site seriously breaks down in two situations. The first is where the outgroups provide no information about the ancestral state of variation in the focal species. In this case, nucleotide variation will be under-estimated if such sites are excluded. The second is where the minor allele in the focal species agrees with the allelic state of the outgroups. In this situation, parsimony tends to over-estimate the probability of the major allele being derived, because it fails to account for the fact that sites with a high frequency of the derived allele tend to be rare. We present a method that corrects this deficiency, which is capable of providing nearly unbiased estimates of ancestral state probabilities on a site-by-site basis and the uSFS.
- Scrutinizing spliceosomes. [Journal Article]
- NRNat Rev Genet 2018 May 15
- The Histone Demethylase KDM5 Is Essential for Larval Growth in Drosophila. [Journal Article]
- GGenetics 2018 May 15
- Regulated gene expression is necessary for developmental and homeostatic processes. The KDM5 family of transcriptional regulators are histone H3 lysine 4 demethylases that can function through both d...
Regulated gene expression is necessary for developmental and homeostatic processes. The KDM5 family of transcriptional regulators are histone H3 lysine 4 demethylases that can function through both demethylase-dependent and independent mechanisms. While loss and overexpression of KDM5 proteins are linked to intellectual disability and cancer, respectively, their normal developmental functions remain less characterized. Drosophilamelanogaster provides an ideal system to investigate KDM5 function, as it encodes a single ortholog in contrast to the four paralogs found in mammalian cells. To examine the consequences of complete loss of KDM5, we generated a null allele of Drosophilakdm5, also known as little imaginal discs (lid), and show that it is essential for viability. Animals lacking KDM5 show a dramatically delayed larval development that coincides with decreased proliferation and increased cell death in wing imaginal discs. Interestingly, this developmental delay is independent of the well-characterized Jumonji C (JmjC) domain-encoded histone demethylase activity of KDM5, suggesting key functions for less characterized domains. Consistent with the phenotypes observed, transcriptome analyses of kdm5 null mutant wing imaginal discs revealed the dysregulation of genes involved in several cellular processes, including cell cycle progression and DNA repair. Together, our analyses reveal KDM5 as a key regulator of larval growth and offer an invaluable tool for defining the biological activities of KDM5 family proteins.
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- An Association Mapping Framework To Account for Potential Sex Difference in Genetic Architectures. [Journal Article]
- GGenetics 2018 May 11
- Over the past few years, genome-wide association studies have identified many trait-associated loci that have different effects on females and males, which increased attention to the genetic architec...
Over the past few years, genome-wide association studies have identified many trait-associated loci that have different effects on females and males, which increased attention to the genetic architecture differences between the sexes. The between-sex differences in genetic architectures can cause a variety of phenomena such as differences in the effect sizes at trait-associated loci, differences in the magnitudes of polygenic background effects, and differences in the phenotypic variances. However, current association testing approaches for dealing with sex, such as including sex as a covariate, cannot fully account for these phenomena and can be suboptimal in statistical power. We present a novel association mapping framework, MetaSex, that can comprehensively account for the genetic architecture differences between the sexes. Through simulations and applications to real data, we show that our framework has superior performance than previous approaches in association mapping.