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Philosophical Transactions of the Royal... Jun 2022'The Apportionment of Human Diversity' stands as a noteworthy intervention, both for the field of human population genetics as well as in the annals of public... (Review)
Review
'The Apportionment of Human Diversity' stands as a noteworthy intervention, both for the field of human population genetics as well as in the annals of public communication of science. Despite the widespread uptake of Lewontin's conclusion that racial classification is of 'virtually no genetic or taxonomic significance', the biomedical research community continues to grapple with whether and how best to account for race in its work. Nowhere is this struggle more apparent than in the latest attempts to translate genetic associations with complex disease risk to clinical use in the form of polygenic risk scores, or PRS. In this perspective piece, we trace current challenges surrounding the appropriate development and clinical application of PRS in diverse patient cohorts to ongoing difficulties deciding which facets of population structure matter, and for what reasons, to human health. Despite numerous analytical innovations, there are reasons that emerge from Lewontin's work to remain sceptical that accounting for population structure in the context of polygenic risk estimation will allow us to more effectively identify and intervene on the significant health disparities which plague marginalized populations around the world. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.
Topics: Genetics, Population; Human Genetics; Humans; Multifactorial Inheritance
PubMed: 35430888
DOI: 10.1098/rstb.2020.0427 -
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 -
Science (New York, N.Y.) Apr 2022Single-cell technology can be used to understand the genetic basis of human diseases.
Single-cell technology can be used to understand the genetic basis of human diseases.
Topics: Disease; Genetics, Population; High-Throughput Nucleotide Sequencing; Humans
PubMed: 35389792
DOI: 10.1126/science.abq0426 -
Methods in Molecular Biology (Clifton,... 2022Population genetics allow to address fundamental questions about the biology of plant pathogens. By testing specific hypotheses, population genetics provide insights...
Population genetics allow to address fundamental questions about the biology of plant pathogens. By testing specific hypotheses, population genetics provide insights into the population genetic variability of pathogens across different geographical areas, time, and associated plant hosts, as well as on the structure and differentiation of populations, and on the possibility that a population is introduced and from where it has originated. In this chapter, basic concepts of population genetics are introduced, as well as the five evolutionary factors affecting populations, that is, mutations, recombination, variation in population size, gene flow, and natural selection. A step-by-step workflow, from sampling to data analysis, on how to perform a genetic analysis of natural populations of plant pathogens is discussed. Increased knowledge of the population biology of pathogens is pivotal to improve management strategies of diseases in agricultural and forest ecosystems.
Topics: Biological Evolution; Ecosystem; Genetics, Population; Plants; Selection, Genetic
PubMed: 35819617
DOI: 10.1007/978-1-0716-2517-0_23 -
Trends in Ecology & Evolution Sep 2019Although social behavior can have a strong genetic component, it can also result in selection on genome structure and function, thereby influencing the evolution of the... (Review)
Review
Although social behavior can have a strong genetic component, it can also result in selection on genome structure and function, thereby influencing the evolution of the genome itself. Here we explore the bidirectional links between social behavior and genome architecture by considering variation in social and/or mating behavior among populations (social polymorphisms) and across closely related species. We propose that social behavior can influence genome architecture via associated demographic changes due to social living. We establish guidelines to exploit emerging whole-genome sequences using analytical approaches that examine genome structure and function at different levels (regulatory vs structural variation) from the perspective of both molecular biology and population genetics in an ecological context.
Topics: Ecology; Genetics, Population; Genome; Social Behavior
PubMed: 31130318
DOI: 10.1016/j.tree.2019.04.011 -
Reports on Progress in Physics.... Aug 2022The growth and evolution of microbial populations is often subjected to advection by fluid flows in spatially extended environments, with immediate consequences for... (Review)
Review
The growth and evolution of microbial populations is often subjected to advection by fluid flows in spatially extended environments, with immediate consequences for questions of spatial population genetics in marine ecology, planktonic diversity and origin of life scenarios. Here, we review recent progress made in understanding this rich problem in the simplified setting of two competing genetic microbial strains subjected to fluid flows. As a pedagogical example we focus on antagonsim, i.e., two killer microorganism strains, each secreting toxins that impede the growth of their competitors (competitive exclusion), in the presence of stationary fluid flows. By solving two coupled reaction-diffusion equations that include advection by simple steady cellular flows composed of characteristic flow motifs in two dimensions (2D), we show how local flow shear and compressibility effects can interact with selective advantage to have a dramatic influence on genetic competition and fixation in spatially distributed populations. We analyze several 1D and 2D flow geometries including sources, sinks, vortices and saddles, and show how simple analytical models of the dynamics of the genetic interface can be used to shed light on the nucleation, coexistence and flow-driven instabilities of genetic drops. By exploiting an analogy with phase separation with nonconserved order parameters, we uncover how thesedrops harness fluid flows for novel evolutionary strategies, even in the presence of number fluctuations, as confirmed by agent-based simulations as well.
Topics: Biological Transport; Diffusion; Genetics, Population; Marine Biology; Plankton
PubMed: 35853344
DOI: 10.1088/1361-6633/ac8231 -
Heredity Mar 2021Discoveries of adaptive gene knockouts and widespread losses of complete genes have in recent years led to a major rethink of the early view that loss-of-function... (Review)
Review
Discoveries of adaptive gene knockouts and widespread losses of complete genes have in recent years led to a major rethink of the early view that loss-of-function alleles are almost always deleterious. Today, surveys of population genomic diversity are revealing extensive loss-of-function and gene content variation, yet the adaptive significance of much of this variation remains unknown. Here we examine the evolutionary dynamics of adaptive loss of function through the lens of population genomics and consider the challenges and opportunities of studying adaptive loss-of-function alleles using population genetics models. We discuss how the theoretically expected existence of allelic heterogeneity, defined as multiple functionally analogous mutations at the same locus, has proven consistent with empirical evidence and why this impedes both the detection of selection and causal relationships with phenotypes. We then review technical progress towards new functionally explicit population genomic tools and genotype-phenotype methods to overcome these limitations. More broadly, we discuss how the challenges of studying adaptive loss of function highlight the value of classifying genomic variation in a way consistent with the functional concept of an allele from classical population genetics.
Topics: Biological Evolution; Genetics, Population; Genomics; Metagenomics; Phenotype
PubMed: 33574599
DOI: 10.1038/s41437-021-00403-2 -
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 -
Human Molecular Genetics Apr 2021During the Trans-Atlantic Slave Trade (TAST), around twelve million Africans were enslaved and forcibly moved from Africa to the Americas and Europe, durably influencing... (Review)
Review
During the Trans-Atlantic Slave Trade (TAST), around twelve million Africans were enslaved and forcibly moved from Africa to the Americas and Europe, durably influencing the genetic and cultural landscape of a large part of humanity since the 15th century. Following historians, archaeologists, and anthropologists, population geneticists have, since the 1950's mainly, extensively investigated the genetic diversity of populations on both sides of the Atlantic. These studies shed new lights into the largely unknown genetic origins of numerous enslaved-African descendant communities in the Americas, by inferring their genetic relationships with extant African, European, and Native American populations. Furthermore, exploring genome-wide data with novel statistical and bioinformatics methods, population geneticists have been increasingly able to infer the last 500 years of admixture histories of these populations. These inferences have highlighted the diversity of histories experienced by enslaved-African descendants, and the complex influences of socioeconomic, political, and historical contexts on human genetic diversity patterns during and after the slave trade. Finally, the recent advances of paleogenomics unveiled crucial aspects of the life and health of the first generation of enslaved-Africans in the Americas. Altogether, human population genetics approaches in the genomic and paleogenomic era need to be coupled with history, archaeology, anthropology, and demography in interdisciplinary research, to reconstruct the multifaceted and largely unknown history of the TAST and its influence on human biological and cultural diversities today. Here, we review anthropological genomics studies published over the past 15 years and focusing on the history of enslaved-African descendant populations in the Americas.
Topics: Americas; Anthropology; Atlantic Ocean; Black People; Enslaved Persons; Enslavement; Genetics, Population; Genomics; History, 15th Century; Humans; Paleography
PubMed: 33331897
DOI: 10.1093/hmg/ddaa271 -
PLoS Computational Biology Apr 2022Population size has long been considered an important driver of cultural diversity and complexity. Results from population genetics, however, demonstrate that in...
Population size has long been considered an important driver of cultural diversity and complexity. Results from population genetics, however, demonstrate that in populations with complex demographic structure or mode of inheritance, it is not the census population size, N, but the effective size of a population, Ne, that determines important evolutionary parameters. Here, we examine the concept of effective population size for traits that evolve culturally, through processes of innovation and social learning. We use mathematical and computational modeling approaches to investigate how cultural Ne and levels of diversity depend on (1) the way traits are learned, (2) population connectedness, and (3) social network structure. We show that one-to-many and frequency-dependent transmission can temporally or permanently lower effective population size compared to census numbers. We caution that migration and cultural exchange can have counter-intuitive effects on Ne. Network density in random networks leaves Ne unchanged, scale-free networks tend to decrease and small-world networks tend to increase Ne compared to census numbers. For one-to-many transmission and different network structures, larger effective sizes are closely associated with higher cultural diversity. For connectedness, however, even small amounts of migration and cultural exchange result in high diversity independently of Ne. Extending previous work, our results highlight the importance of carefully defining effective population size for cultural systems and show that inferring Ne requires detailed knowledge about underlying cultural and demographic processes.
Topics: Biological Evolution; Computer Simulation; Genetics, Population; Phenotype; Population Density
PubMed: 35395004
DOI: 10.1371/journal.pcbi.1009430