scholarly journals Applicability of the mutation-selection balance model to population genetics of heterozygous protein-truncating variants in humans

2018 ◽  
Author(s):  
Donate Weghorn ◽  
Daniel J. Balick ◽  
Christopher Cassa ◽  
Jack Kosmicki ◽  
Mark J. Daly ◽  
...  
Keyword(s):  
Population Genetics ◽  
De Novo ◽  
Demographic History ◽  
Purifying Selection ◽  
Population History ◽  
Balance Model ◽  
Stochastic Force ◽  
Drift Estimation ◽  
Human Genes ◽  
Per Gene

AbstractThe fate of alleles in the human population is believed to be highly affected by the stochastic force of genetic drift. Estimation of the strength of natural selection in humans generally necessitates a careful modeling of drift including complex effects of the population history and structure. Protein truncating variants (PTVs) are expected to evolve under strong purifying selection and to have a relatively high per-gene mutation rate. Thus, it is appealing to model the population genetics of PTVs under a simple deterministic mutation-selection balance, as has been proposed earlier [1]. Here, we investigated the limits of this approximation using both computer simulations and data-driven approaches. Our simulations rely on a model of demographic history estimated from 33,370 individual exomes of the Non-Finnish European subset of the ExAC dataset [2]. Additionally, we compared the African and European subset of the ExAC study and analyzed de novo PTVs. We show that the mutation-selection balance model is applicable to the majority of human genes, but not to genes under the weakest selection.

scholarly journals Applicability of the Mutation–Selection Balance Model to Population Genetics of Heterozygous Protein-Truncating Variants in Humans

2019 ◽  
Vol 36 (8) ◽  
pp. 1701-1710 ◽  
Author(s):  
Donate Weghorn ◽  
Daniel J Balick ◽  
Christopher Cassa ◽  
Jack A Kosmicki ◽  
Mark J Daly ◽  
...  
Keyword(s):  
Population Genetics ◽  
De Novo ◽  
Demographic History ◽  
Purifying Selection ◽  
Population History ◽  
Balance Model ◽  
Data Set ◽  
Stochastic Force ◽  
Drift Estimation ◽  
Human Genes

Abstract The fate of alleles in the human population is believed to be highly affected by the stochastic force of genetic drift. Estimation of the strength of natural selection in humans generally necessitates a careful modeling of drift including complex effects of the population history and structure. Protein-truncating variants (PTVs) are expected to evolve under strong purifying selection and to have a relatively high per-gene mutation rate. Thus, it is appealing to model the population genetics of PTVs under a simple deterministic mutation–selection balance, as has been proposed earlier (Cassa et al. 2017). Here, we investigated the limits of this approximation using both computer simulations and data-driven approaches. Our simulations rely on a model of demographic history estimated from 33,370 individual exomes of the Non-Finnish European subset of the ExAC data set (Lek et al. 2016). Additionally, we compared the African and European subset of the ExAC study and analyzed de novo PTVs. We show that the mutation–selection balance model is applicable to the majority of human genes, but not to genes under the weakest selection.

scholarly journals High quality whole genome sequence of an abundant Holarctic odontocete, the harbour porpoise (Phocoena phocoena)

2018 ◽  
Author(s):  
Marijke Autenrieth ◽  
Stefanie Hartmann ◽  
Ljerka Lah ◽  
Anna Roos ◽  
Alice B. Dennis ◽  
...  
Keyword(s):  
Genome Assembly ◽  
De Novo ◽  
Bos Taurus ◽  
Demographic History ◽  
Harbour Porpoise ◽  
Population History ◽  
Whole Genome Sequence ◽  
Phocoena Phocoena ◽  
Total Size ◽  
High Level

AbstractThe harbour porpoise (Phocoena phocoena) is a highly mobile cetacean found in waters across the Northern hemisphere. It occurs in coastal water and inhabits water basins that vary broadly in salinity, temperature, and food availability. These diverse habitats could drive differentiation among populations. Here we report the first harbour porpoise genome, assembled de novo from a Swedish Kattegat individual. The genome is one of the most complete cetacean genomes currently available, with a total size of 2.7 Gb and 50% of the total length found in just 34 scaffolds. Using the largest 122 scaffolds, we were able to validate a high level of homology to the chromosome-level genome assembly of the closest related species for which such resource was available, the domestic cattle (Bos taurus). The draft annotation comprises 22,154 predicted gene models, which we further annotated through matches to the NCBI nucleotide database, GO categorization, and motif prediction. To infer the adaptive abilities of this species, as well as their population history, we performed a Bayesian skyline analysis, and produced results that are concordant with the demographic history of this species, including expansion and fragmentation events. Overall, this genome assembly, together with the draft annotation, represents a crucial addition to the limited genetic markers currently available for the study of porpoises and Phocoenidae conservation, phylogeny, and evolution.

scholarly journals Overcoming constraints on the detection of recessive selection in human genes from population frequency data

2021 ◽  
Author(s):  
Daniel J Balick ◽  
Daniel M Jordan ◽  
Shamil Sunyaev ◽  
Ron Do
Keyword(s):  
Population Genetics ◽  
Population Sample ◽  
Purifying Selection ◽  
Selective Constraint ◽  
Monogenic Disorders ◽  
Genetics Research ◽  
Disease Gene Discovery ◽  
Gene Sets ◽  
Human Genes ◽  
Recessive Genes

The identification of genes that evolve under recessive natural selection is a longstanding goal of population genetics research with important applications to disease gene discovery. We found that commonly used methods to evaluate selective constraint at the gene level are highly sensitive to genes under heterozygous selection but ubiquitously fail to detect recessively evolving genes. Additionally, more sophisticated likelihood-based methods designed to detect recessivity similarly lack power for a human gene of realistic length from current population sample sizes. However, extensive simulations suggested that recessive genes may be detectable in aggregate. Here, we offer a method informed by population genetics simulations designed to detect recessive purifying selection in gene sets. Applying this to empirical gene sets produced significant enrichments for strong recessive selection in genes previously inferred to be under recessive selection in a consanguineous cohort and in genes involved in autosomal recessive monogenic disorders.

scholarly journals An Integrated Framework for the Inference of Viral Population History From Reconstructed Genealogies

Genetics ◽  
2000 ◽  
Vol 155 (3) ◽  
pp. 1429-1437
Author(s):  
Oliver G Pybus ◽  
Andrew Rambaut ◽  
Paul H Harvey
Keyword(s):  
Maximum Likelihood ◽  
Sequence Data ◽  
Demographic History ◽  
Population History ◽  
Maximum Likelihood Estimates ◽  
Viral Population ◽  
True Parameter ◽  
Subtype B ◽  
Exponential Growth Model ◽  
Parameter Values

Abstract We describe a unified set of methods for the inference of demographic history using genealogies reconstructed from gene sequence data. We introduce the skyline plot, a graphical, nonparametric estimate of demographic history. We discuss both maximum-likelihood parameter estimation and demographic hypothesis testing. Simulations are carried out to investigate the statistical properties of maximum-likelihood estimates of demographic parameters. The simulations reveal that (i) the performance of exponential growth model estimates is determined by a simple function of the true parameter values and (ii) under some conditions, estimates from reconstructed trees perform as well as estimates from perfect trees. We apply our methods to HIV-1 sequence data and find strong evidence that subtypes A and B have different demographic histories. We also provide the first (albeit tentative) genetic evidence for a recent decrease in the growth rate of subtype B.

scholarly journals De Novo Genome Assembly of Limpet Bathyacmaea lactea (Gastropoda: Pectinodontidae): The First Reference Genome of a Deep-Sea Gastropod Endemic to Cold Seeps

2020 ◽  
Vol 12 (6) ◽  
pp. 905-910 ◽  
Author(s):  
Ruoyu Liu ◽  
Kun Wang ◽  
Jun Liu ◽  
Wenjie Xu ◽  
Yang Zhou ◽  
...  
Keyword(s):  
Deep Sea ◽  
Metal Ion ◽  
De Novo ◽  
Demographic History ◽  
Gene Families ◽  
Phylogenetic Position ◽  
Cold Seeps ◽  
Nitrogen And Phosphorus ◽  
De Novo Genome Assembly ◽  
A Genome

Abstract Cold seeps, characterized by the methane, hydrogen sulfide, and other hydrocarbon chemicals, foster one of the most widespread chemosynthetic ecosystems in deep sea that are densely populated by specialized benthos. However, scarce genomic resources severely limit our knowledge about the origin and adaptation of life in this unique ecosystem. Here, we present a genome of a deep-sea limpet Bathyacmaea lactea, a common species associated with the dominant mussel beds in cold seeps. We yielded 54.6 gigabases (Gb) of Nanopore reads and 77.9-Gb BGI-seq raw reads, respectively. Assembly harvested a 754.3-Mb genome for B. lactea, with 3,720 contigs and a contig N50 of 1.57 Mb, covering 94.3% of metazoan Benchmarking Universal Single-Copy Orthologs. In total, 23,574 protein-coding genes and 463.4 Mb of repetitive elements were identified. We analyzed the phylogenetic position, substitution rate, demographic history, and TE activity of B. lactea. We also identified 80 expanded gene families and 87 rapidly evolving Gene Ontology categories in the B. lactea genome. Many of these genes were associated with heterocyclic compound metabolism, membrane-bounded organelle, metal ion binding, and nitrogen and phosphorus metabolism. The high-quality assembly and in-depth characterization suggest the B. lactea genome will serve as an essential resource for understanding the origin and adaptation of life in the cold seeps.

Phylogeographic structure and gene flow of Himalayan snowcock (Tetraogallus himalayensis)

2010 ◽  
Vol 60 (4) ◽  
pp. 449-465
Author(s):  
Wen Longying ◽  
Zhang Lixun ◽  
An Bei ◽  
Luo Huaxing ◽  
Liu Naifa ◽  
...  
Keyword(s):  
Demographic History ◽  
Phylogenetic Analyses ◽  
Divergence Time ◽  
Population Expansion ◽  
Population History ◽  
Tibet Plateau ◽  
Phylogeographic Structure ◽  
Mitochondrial Cytochrome B ◽  
History Of ◽  
Qinghai Tibet Plateau

AbstractWe have used phylogeographic methods to investigate the genetic structure and population history of the endangered Himalayan snowcock (Tetraogallus himalayensis) in northwestern China. The mitochondrial cytochrome b gene was sequenced of 102 individuals sampled throughout the distribution range. In total, we found 26 different haplotypes defined by 28 polymorphic sites. Phylogenetic analyses indicated that the samples were divided into two major haplogroups corresponding to one western and one eastern clade. The divergence time between these major clades was estimated to be approximately one million years. An analysis of molecular variance showed that 40% of the total genetic variability was found within local populations, 12% among populations within regional groups and 48% among groups. An analysis of the demographic history of the populations suggested that major expansions have occurred in the Himalayan snowcock populations and these correlate mainly with the first and the second largest glaciations during the Pleistocene. In addition, the data indicate that there was a population expansion of the Tianshan population during the uplift of the Qinghai-Tibet Plateau, approximately 2 million years ago.

scholarly journals Population Dynamics in Pre-Modern China

2013 ◽  
Author(s):  
Zhongwei Zhao
Keyword(s):  
Economic Development ◽  
Population Growth ◽  
Chinese Population ◽  
Environmental Changes ◽  
Demographic History ◽  
Social Institutions ◽  
Population History ◽  
Chinese History ◽  
Population Changes ◽  
The Past

China constituted one of the earliest civilizations in the world. During most of the past two millennia, China was also one of the most advanced economies and the home of around a quarter of the world’s population. By the start of the first millennium, the Chinese population was already about sixty million. In the next two thousand years, China’s population growth and economic development significantly influenced the world’s population changes and history. Partly for these reasons, in the study of population and social history, China’s historical population growth, demographic regimes, marriage patterns, and household formation systems are frequently used as examples in the discussion of population changes, microsocial structure, and their relationships with natural resources and economic development in past times. Population changes were one of the key components of Chinese history. The size and density of the population, the rise and fall of fertility and mortality, and the increase and decrease of population movements were not only related to demographic factors such as age structure. They were also strongly affected by political and economic conditions, social institutions and cultural traditions, and natural and social environments. Therefore, studies of demographic history, those conducted recently in particular, often shed new light on economic, political, social, and environmental changes in the past. This bibliography, through reviewing major works published in Chinese and English, provides an introduction to China’s main historical population data sources, major research questions, and debates in the study of Chinese population history. It also introduces recent advances in Chinese historical demography and important research findings made by these developments.

scholarly journals An Improved Human smORF Annnotation Workflow Combining De Novo Transcriptome Assembly and Ribo-Seq

2019 ◽  
Author(s):  
Thomas F. Martinez ◽  
Qian Chu ◽  
Cynthia Donaldson ◽  
Dan Tan ◽  
Maxim N. Shokhirev ◽  
...  
Keyword(s):  
De Novo ◽  
Transcriptome Assembly ◽  
Human Leukocyte ◽  
Open Reading Frames ◽  
Translation Efficiency ◽  
Proteomics Data ◽  
Protein Coding ◽  
Leukocyte Antigen ◽  
Human Genes ◽  
Small Open Reading Frames

Protein-coding small open reading frames (smORFs) are emerging as an important class of genes, however, the coding capacity of smORFs in the human genome is unclear. By integrating de novo transcriptome assembly and Ribo-Seq, we confidently annotate thousands of novel translated smORFs in three human cell lines. We find that smORF translation prediction is noisier than for annotated coding sequences, underscoring the importance of analyzing multiple experiments and footprinting conditions. These smORFs are located within non-coding and antisense transcripts, the UTRs of mRNAs, and unannotated transcripts. Analysis of RNA levels and translation efficiency during cellular stress identifies regulated smORFs, providing an approach to select smORFs for further investigation. Sequence conservation and signatures of positive selection indicate that encoded microproteins are likely functional. Additionally, proteomics data from enriched human leukocyte antigen complexes validates the translation of hundreds of smORFs and positions them as a source of novel antigens. Thus, smORFs represent a significant number of important, yet unexplored human genes.

scholarly journals Population structure and demographic history of the chukar partridge Alectoris chukar in China

2013 ◽  
Vol 59 (4) ◽  
pp. 458-474 ◽  
Author(s):  
Sen Song ◽  
Shijie Bao ◽  
Ying Wang ◽  
Xinkang Bao ◽  
Bei An ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Gene Flow ◽  
North America ◽  
Demographic History ◽  
Population Expansion ◽  
Northwest China ◽  
Population History ◽  
Extant Species ◽  
History Of ◽  
Chukar Partridge

Abstract Pleistocene climate fluctuations have shaped the patterns of genetic diversity observed in extant species. Although the effects of recent glacial cycles on genetic diversity have been well studied on species in Europe and North America, genetic legacy of species in the Pleistocene in north and northwest of China where glaciations was not synchronous with the ice sheet development in the Northern Hemisphere or or had little or no ice cover during the glaciations’ period, remains poorly understood. Here we used phylogeographic methods to investigate the genetic structure and population history of the chukar partridge Alec-toris chukar in north and northwest China. A 1,152 – 1,154 bp portion of the mtDNA CR were sequenced for all 279 specimens and a total number of 91 haplotypes were defined by 113 variable sites. High levels of gene flow were found and gene flow estimates were greater than 1 for most population pairs in our study. The AMOVA analysis showed that 81% and 16% of the total genetic variability was found within populations and among populations within groups, respectively. The demographic history of chukar was examined using neutrality tests and mismatch distribution analyses and results indicated Late Pleistocene population expansion. Results revealed that most populations of chukar experienced population expansion during 0.027 ? 0.06 Ma. These results are at odds with the results found in Europe and North America, where population expansions occurred after Last Glacial Maximum (LGM, 0.023 to 0.018 Ma). Our results are not consistent with the results from avian species of Tibetan Plateau, either, where species experienced population expansion following the retreat of the extensive glaciation period (0.5 to 0.175 Ma).

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