Adaptations to Climate in Candidate Genes for Common Metabolic Disorders

Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel) and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T) that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders.</p

PENINGKATAN KETERAMPILAN MENULIS TEKS EKSPOSISI MELALUI PENGGUNAAN STRATEGI PEMBELAJARAN THINK TALK WRITE DAN MEDIA AUDIO VISUAL ( Penelitian Tindakan Kelas pada Siswa Kelas X IPS 2 SMA N 1 Surakarta Tahun Pelajaran 2017/2018)

Yustina Dwinuryati.2017. Peningkatan Keterampilan menulis Teks Eksposisi melalui Penggunaan Strategi Pembelajaran Think, Talk, Write dan Media Audio Visual (Penelitian Tindakan Kelas pada Siswa Kelas X IPS 2 SMA N 1 Surakarta Tahun Pelajaran 2017/2018). Tesis. Pembimbing: Prof. Dr. Andayani, M.Pd. Kopembimbing: Prof. Dr. Retno Winarni, M.Pd. Program Studi Magister Pendidikan Bahasa Indonesia, Fakultas Keguruan dan Ilmu Pendidikan, Universitas Sebelas Maret Surakarta. ABSTRAK Keterampilan menulis merupakan keterampilan berbahasa tingkat tinggi dan harus diajarkan kepada siswa di Sekolah Menengah Atas. Salah satu keterampilan menulis yang harus diajarkan kepada siswa kelas X sesuai Kurikulum 2013 Revisi adalah menulis teks eksposisi. Pembelajaran keterampilan menulis teks eksposisi di kelas X IPS2 SMA N 1 Surakarta mengalami permasalahan baik dari sisi motivasi belajar maupun keterampilan menulis siswa. Penelitian ini bertujuan untuk meningkatkan: (1) motivasi belajar menulis teks eksposisi siswa kelas X IPS 2 SMA Negeri 1 Surakarta dengan strategi pembelajaran think talk write dan penggunaan media audio visual dan (2) keterampilan menulis teks eksposisi siswa kelas X IPS 2 SMA Negeri 1 Surakarta dengan strategi pembelajaran think talk write dan media audio visual. Strategi penelitian berupa Penelitian Tindakan Kelas. Data penelitian bersumber dari proses pembelajaran, informan, hasil tes menulis teks eksposisi, dan dokumen. Teknik pengumpulan data dengan pengamatan, kajian dokumen, wawancara, dan tes. Uji validitas data menggunakan teknik triangulasi sumber data dan triangulasi metode. Teknik analisis data menggunakan teknik deskriptif komparatif dan analisis kritis. Hasil penelitian menunjukkan bahwa penerapan strategi pembelajaran think, talk, write dan penggunaan media audio visual pada siswa kelas X IPS2 SMA N I Surakarta dapat meningkatkan motivasi belajar dan keterampilan menulis teks eksposisi dari siklus 1 ke siklus 2. Hal itu dibuktikan adanya perubahan dan peningkatan motivasi belajar dan keterampilan menulis teks eksposisi siswa: (1) motivasi siswa meningkat dari siklus 1 sebesar 68% menjadi 82% pada siklus 2 dan (2) keterampilan menulis teks eksposisi meningkat dari siklus 1 sebesar 76% meningkat menjadi 88% pada siklus 2. Kata kunci: teks eksposisi, motivasi, strategi think talk write, audio visua

Broad-Scale Recombination Patterns Underlying Proper Disjunction in Humans

Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale. To assess the nature and stringency of constraints on human recombination, we examined crossover patterns in transmissions to viable, non-trisomic offspring, using dense genotyping data collected in a large set of pedigrees. Our analysis supports a requirement for one chiasma per chromosome rather than per arm to ensure proper disjunction, with additional chiasmata occurring in proportion to physical length. The requirement is not absolute, however, as chromosome 21 seems to be frequently transmitted properly in the absence of a chiasma in females, a finding that raises the possibility of a back-up mechanism aiding in its correct segregation. We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference. These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans

A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes

GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and general functional consequences remain poorly understood. gBGC is difficult to incorporate into models of molecular evolution and so far has primarily been studied using summary statistics from genomic comparisons. Here, we introduce a new probabilistic model that captures the joint effects of natural selection and gBGC on nucleotide substitution patterns, while allowing for correlations along the genome in these effects. We implemented our model in a computer program, called phastBias, that can accurately detect gBGC tracts about 1 kilobase or longer in simulated sequence alignments. When applied to real primate genome sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide differences. These tracts fall in clusters, particularly in subtelomeric regions; they are enriched for recombination hotspots and fast-evolving sequences; and they display an ongoing fixation preference for G and C alleles. They are also significantly enriched for disease-associated polymorphisms, suggesting that they contribute to the fixation of deleterious alleles. The gBGC tracts provide a unique window into historical recombination processes along the human and chimpanzee lineages. They supply additional evidence of long-term conservation of megabase-scale recombination rates accompanied by rapid turnover of hotspots. Together, these findings shed new light on the evolutionary, functional, and disease implications of gBGC. The phastBias program and our predicted tracts are freely available. © 2013 Capra et al

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Adaptations to Climate-Mediated Selective Pressures in Humans

Humans inhabit a remarkably diverse range of environments, and adaptation through natural selection has likely played a central role in the capacity to survive and thrive in extreme climates. Unlike numerous studies that used only population genetic data to search for evidence of selection, here we scan the human genome for selection signals by identifying the SNPs with the strongest correlations between allele frequencies and climate across 61 worldwide populations. We find a striking enrichment of genic and nonsynonymous SNPs relative to non-genic SNPs among those that are strongly correlated with these climate variables. Among the most extreme signals, several overlap with those from GWAS, including SNPs associated with pigmentation and autoimmune diseases. Further, we find an enrichment of strong signals in gene sets related to UV radiation, infection and immunity, and cancer. Our results imply that adaptations to climate shaped the spatial distribution of variation in humans

The likelihood of gene trees under selective models

The extent to which natural selection shapes diversity within populations is a key question for population genetics. Thus, there is considerable interest in quantifying the strength of selection. In this thesis a full likelihood approach for inference about selection at a single site within an otherwise neutral fully-linked sequence of sites is developed. Integral to many of the ideas introduced in this thesis is the reversibility of the diffusion process, and some past approaches to this concept are reviewed. A coalescent model of evolution is used to model the ancestry of a sample of DNA sequences which have the selected site segregating. A novel method for simulating the coalescent with selection, acting at a single biallelic site, is described. Selection is incorporated through modelling the frequency of the selected and neutral allelic classes stochastically back in time. The ancestry is then simulated using a subdivided population model considering the population frequencies through time as variable population sizes. The approach is general and can be used for any selection scheme at a biallelic locus. The mutation model, for the selected and neutral sites, is the infinitely-many-sites model where there is no back or parallel mutation at sites. This allows a unique perfect phylogeny, a gene tree, to be constructed from the configuration of mutations on the sample sequences. An importance sampling algorithm is described to explore over coalescent tree space consistent with this gene tree. The method is used to assess the evidence for selection in a number of data sets. These are as follows: a partial selective sweep in the G6PD gene (Verrelli et al., 2002); a recent full sweep in the Factor IX gene (Harris and Hey, 2001); and balancing selection in the DCP1 gene (Rieder et al., 1999). Little evidence of the action of selection is found in the data set of Verrelli et al. (2002) and the data set of Rieder et al. (1999) seems inconsistent with the model of balancing selection. The patterns of diversity in the data set of Harris and Hey (2001) offer support of the hypothesis of a full sweep.</p