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Genes Apr 2024The dialogue between population genetics and evolutionary biology, which historically followed separate paths, has now developed into a complex and interdisciplinary...
The dialogue between population genetics and evolutionary biology, which historically followed separate paths, has now developed into a complex and interdisciplinary field of study [...].
Topics: Genetics, Population; Genomics; Humans; Evolution, Molecular; Population Dynamics; Genetic Variation; Animals; Biological Evolution
PubMed: 38674381
DOI: 10.3390/genes15040446 -
Animal Genetics Dec 2023Half a century ago, a seminal article on the hitchhiking effect by Smith and Haigh inaugurated the concept of the selection signature. Selective sweeps are characterised... (Review)
Review
Half a century ago, a seminal article on the hitchhiking effect by Smith and Haigh inaugurated the concept of the selection signature. Selective sweeps are characterised by the rapid spread of an advantageous genetic variant through a population and hence play an important role in shaping evolution and research on genetic diversity. The process by which a beneficial allele arises and becomes fixed in a population, leading to a increase in the frequency of other linked alleles, is known as genetic hitchhiking or genetic draft. Kimura's neutral theory and hitchhiking theory are complementary, with Kimura's neutral evolution as the 'null model' and positive selection as the 'signal'. Both are widely accepted in evolution, especially with genomics enabling precise measurements. Significant advances in genomic technologies, such as next-generation sequencing, high-density SNP arrays and powerful bioinformatics tools, have made it possible to systematically investigate selection signatures in a variety of species. Although the history of selection signatures is relatively recent, progress has been made in the last two decades, owing to the increasing availability of large-scale genomic data and the development of computational methods. In this review, we embark on a journey through the history of research on selective sweeps, ranging from early theoretical work to recent empirical studies that utilise genomic data.
Topics: Animals; Selection, Genetic; Models, Genetic; Alleles; Computational Biology; Genomics; Genetics, Population
PubMed: 37710403
DOI: 10.1111/age.13355 -
Molecular Biology and Evolution May 2024This perspective article offers a meditation on FST and other quantities developed by Sewall Wright to describe the population structure, defined as any departure from...
This perspective article offers a meditation on FST and other quantities developed by Sewall Wright to describe the population structure, defined as any departure from reproduction through random union of gametes. Concepts related to the F-statistics draw from studies of the partitioning of variation, identity coefficients, and diversity measures. Relationships between the first two approaches have recently been clarified and unified. This essay addresses the third pillar of the discussion: Nei's GST and related measures. A hierarchy of probabilities of identity-by-state provides a description of the relationships among levels of a structured population with respect to genetic diversity. Explicit expressions for the identity-by-state probabilities are determined for models of structured populations undergoing regular inbreeding and recurrent mutation. Levels of genetic diversity within and between subpopulations reflect mutation as well as migration. Accordingly, indices of the population structure are inherently locus-specific, contrary to the intentions of Wright. Some implications of this locus-specificity are explored.
Topics: Models, Genetic; Genetic Variation; Genetics, Population; Mutation; Inbreeding
PubMed: 38696269
DOI: 10.1093/molbev/msae083 -
Ecology Letters Sep 2023Growing evidence suggests that temporally fluctuating environments are important in maintaining variation both within and between species. To date, however, studies of... (Review)
Review
Growing evidence suggests that temporally fluctuating environments are important in maintaining variation both within and between species. To date, however, studies of genetic variation within a population have been largely conducted by evolutionary biologists (particularly population geneticists), while population and community ecologists have concentrated more on diversity at the species level. Despite considerable conceptual overlap, the commonalities and differences of these two alternative paradigms have yet to come under close scrutiny. Here, we review theoretical and empirical studies in population genetics and community ecology focusing on the 'temporal storage effect' and synthesise theories of diversity maintenance across different levels of biological organisation. Drawing on Chesson's coexistence theory, we explain how temporally fluctuating environments promote the maintenance of genetic variation and species diversity. We propose a further synthesis of the two disciplines by comparing models employing traditional frequency-dependent dynamics and those adopting density-dependent dynamics. We then address how temporal fluctuations promote genetic and species diversity simultaneously via rapid evolution and eco-evolutionary dynamics. Comparing and synthesising ecological and evolutionary approaches will accelerate our understanding of diversity maintenance in nature.
Topics: Biological Evolution; Population Dynamics; Genetics, Population
PubMed: 37840028
DOI: 10.1111/ele.14286 -
G3 (Bethesda, Md.) Jul 2023Inference of demographic histories of species and populations is one of the central problems in population genetics. It is usually stated as an optimization problem:...
Inference of demographic histories of species and populations is one of the central problems in population genetics. It is usually stated as an optimization problem: find a model's parameters that maximize a certain log-likelihood. This log-likelihood is often expensive to evaluate in terms of time and hardware resources, critically more so for larger population counts. Although genetic algorithm-based solution has proven efficient for demographic inference in the past, it struggles to deal with log-likelihoods in the setting of more than three populations. Different tools are therefore needed to handle such scenarios. We introduce a new optimization pipeline for demographic inference with time consuming log-likelihood evaluations. It is based on Bayesian optimization, a prominent technique for optimizing expensive black box functions. Comparing to the existing widely used genetic algorithm solution, we demonstrate new pipeline's superiority in the limited time budget setting with four and five populations, when using the log-likelihoods provided by the moments tool.
Topics: Bayes Theorem; Likelihood Functions; Models, Genetic; Genetics, Population; Demography
PubMed: 37070782
DOI: 10.1093/g3journal/jkad080 -
Urolithiasis Aug 2023Cystine stone is a Mendelian genetic disease caused by SLC3A1 or SLC7A9. In this study, we aimed to estimate the genetic prevalence of cystine stones and compare it with...
BACKGROUND
Cystine stone is a Mendelian genetic disease caused by SLC3A1 or SLC7A9. In this study, we aimed to estimate the genetic prevalence of cystine stones and compare it with the clinical prevalence to better understand the disease etiology.
METHODS
We analyzed genetic variants in the general population using the 1000 Genomes project and the Human Gene Mutation Database to extract all SLC3A1 and SLC7A9 pathogenic variants. All variants procured from both databases were intersected. Pathogenic allele frequency, carrier rate, and affected rate were calculated and estimated based on Hardy-Weinberg equilibrium.
RESULTS
We found that 9 unique SLC3A1 pathogenic variants were carried by 26 people and 5 unique SLC7A9 pathogenic variants were carried by 12 people, all of whom were heterozygote carriers. No homozygote, compoun d heterozygote, or double heterozygote was identified in the 1000 Genome database. Based on the Hardy-Weinberg equilibrium, the calculated genetic prevalence of cystine stone disease is 1 in 30,585.
CONCLUSION
The clinical prevalence of cystine stone has been previously reported as 1 in 7,000, a notably higher figure than the genetic prevalence of 1 in 30,585 calculated in this study. This suggests that the etiology of cystine stone is more complex than what our current genetic knowledge can explain. Possible factors that may contribute to this difference include novel causal genes, undiscovered pathogenic variants, alternative inheritance models, founder effects, epigenetic modifications, environmental factors, or other modifying factors. Further investigation is needed to fully understand the etiology of cystine stone.
Topics: Humans; Amino Acid Transport Systems, Basic; Cystine; Cystinuria; Gene Frequency; Genetics, Population; Mutation
PubMed: 37561200
DOI: 10.1007/s00240-023-01473-z -
Trends in Ecology & Evolution Oct 2023Our ability to assess the threat posed by the genetic load to small and declining populations has been greatly improved by advances in genome sequencing and... (Review)
Review
Our ability to assess the threat posed by the genetic load to small and declining populations has been greatly improved by advances in genome sequencing and computational approaches. Yet, considerable confusion remains around the definitions of the genetic load and its dynamics, and how they impact individual fitness and population viability. We illustrate how both selective purging and drift affect the distribution of deleterious mutations during population size decline and recovery. We show how this impacts the composition of the genetic load, and how this affects the extinction risk and recovery potential of populations. We propose a framework to examine load dynamics and advocate for the introduction of load estimates in the management of endangered populations.
Topics: Genetics, Population; Genetic Load; Population Density; Inbreeding; Genetic Variation
PubMed: 37344276
DOI: 10.1016/j.tree.2023.05.008 -
Danish Medical Journal Nov 2023The history of the Greenlandic population has contributed to a unique genetic composition in which high-impact and often novel genetic variants segregate at a high... (Review)
Review
The history of the Greenlandic population has contributed to a unique genetic composition in which high-impact and often novel genetic variants segregate at a high frequency. As a result, research in smaller populations like the Greenlandic has the potential to reveal genetic variation and associations that are not present or discoverable in other populations. In this review, we provide a summary of our research in Greenlanders and our findings of genetic variants with high impact on metabolic health, and outline the implications that this research has for the equitable distribution of genomic precision medicine.
Topics: Humans; Greenland; Genetics, Population
PubMed: 38018706
DOI: No ID Found -
Methods in Molecular Biology (Clifton,... 2024The allele frequency net database (AFND, http://www.allelefrequencies.net ) is an online web-based repository that contains information on the frequencies of...
The allele frequency net database (AFND, http://www.allelefrequencies.net ) is an online web-based repository that contains information on the frequencies of immune-related genes and their corresponding alleles in worldwide human populations. At present, the website contains data from 1784 population samples in more than 14 million individuals from 129 countries on the frequency of genes from different polymorphic regions including data for the human leukocyte antigen (HLA) system. In addition, over the last four years, AFND has also incorporated genotype raw data from 85,000 individuals comprising 215 population samples from 39 countries. Moreover, more population data sets containing next generation sequencing data spanning >3 million individuals have been added. This resource has been widely used in a variety of contexts such as histocompatibility, immunology, epidemiology, pharmacogenetics, epitope prediction algorithms for population coverage in vaccine development, population genetics, among many others. In this chapter, we present an update of the most used searching mechanisms as described in a previous volume and some of the latest developments included in AFND.
Topics: Humans; Gene Frequency; Databases, Genetic; Genetics, Population; HLA Antigens; Alleles; Computational Biology; Internet; Web Browser; Genotype; High-Throughput Nucleotide Sequencing
PubMed: 38907888
DOI: 10.1007/978-1-0716-3874-3_2 -
Nature Genetics May 2024Human pluripotent stem (hPS) cells can, in theory, be differentiated into any cell type, making them a powerful in vitro model for human biology. Recent technological... (Review)
Review
Human pluripotent stem (hPS) cells can, in theory, be differentiated into any cell type, making them a powerful in vitro model for human biology. Recent technological advances have facilitated large-scale hPS cell studies that allow investigation of the genetic regulation of molecular phenotypes and their contribution to high-order phenotypes such as human disease. Integrating hPS cells with single-cell sequencing makes identifying context-dependent genetic effects during cell development or upon experimental manipulation possible. Here we discuss how the intersection of stem cell biology, population genetics and cellular genomics can help resolve the functional consequences of human genetic variation. We examine the critical challenges of integrating these fields and approaches to scaling them cost-effectively and practically. We highlight two areas of human biology that can particularly benefit from population-scale hPS cell studies, elucidating mechanisms underlying complex disease risk loci and evaluating relationships between common genetic variation and pharmacotherapeutic phenotypes.
Topics: Humans; Genomics; Genetics, Population; Pluripotent Stem Cells; Genetic Variation; Phenotype; Single-Cell Analysis; Disease
PubMed: 38741017
DOI: 10.1038/s41588-024-01731-9