DOCSLIB.ORG

Changes in Life History and Population Size Can Explain the Relative Neutral Diversity Levels on X and Autosomes in Extant Human Populations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Changes in Life History and Population Size Can Explain the Relative Neutral Diversity Levels on X and Autosomes in Extant Human Populations Changes in life history and population size can explain the relative neutral diversity levels on X and autosomes in extant human populations Guy Amstera,1, David A. Murphya, William R. Milligana, and Guy Sellaa,b,c,1 aDepartment of Biological Sciences, Columbia University, New York, NY 10027; bDepartment of Systems Biology, Columbia University, New York, NY 10032; and cProgram for Mathematical Genomics, Columbia University, New York, NY 10032 Edited by Brian Charlesworth, University of Edinburgh, Edinburgh, United Kingdom, and approved July 7, 2020 (received for review October 22, 2019) In human populations, the relative levels of neutral diversity on generally—the effects of selection at linked sites should be stronger the X and autosomes differ markedly from each other and from on the X (ref. 18, but see ref. 3). To evaluate these effects empiri- the naïve theoretical expectation of 3/4. Here we propose an ex- cally, several studies have examined how diversity levels on the X and planation for these differences based on new theory about the autosomes vary with genetic distance from putatively selected re- effects of sex-specific life history and given pedigree-based esti- gions, for example from coding and conserved noncoding regions mates of the dependence of human mutation rates on sex and (11, 13–15, 19, 20). In most hominids, including humans, such age. We demonstrate that life history effects, particularly longer comparisons confirm the theoretical expectation that selection at generation times in males than in females, are expected to have linked loci reduces X:A diversity ratios (11, 15, 20). They further had multiple effects on human X-to-autosome (X:A) diversity ra- suggest that the effects are minimal sufficiently far from genes (11, tios, as a result of male-biased mutation rates, the equilibrium X:A 19), thereby providing an opportunity to examine the effects of ratio of effective population sizes, and the differential responses other factors shaping X:A diversity ratios in isolation by considering to changes in population size. We also show that the standard regions that are minimally affected. approach of using divergence between species to correct for male Even far from genes, however, the X:A diversity ratios in mutation bias results in biased estimates of X:A effective popula- humans and other hominids differ from the naïve expectation of tion size ratios. We obtain alternative estimates using pedigree- 3/4 (11, 13, 14). Diversity levels on the X and autosomes are EVOLUTION based estimates of the male mutation bias, which reveal that X:A typically divided by divergence from an outgroup (e.g., diver- ratios of effective population sizes are considerably greater than gence from orangutan or rhesus macaque is used to normalize previously appreciated. Finally, we find that the joint effects of diversity levels in humans) in order to control for the effects of historical changes in life history and population size can explain higher mutation rates in males and variation in mutation rates the observed X:A diversity ratios in extant human populations. along the genome (9). The normalized estimates of X:A diversity Our results suggest that ancestral human populations were highly ratios in regions far from genes range between 3/4 and 1 among polygynous, that non-African populations experienced a substan- human populations, generally decreasing with the distance from tial reduction in polygyny and/or increase in the male-to-female Africa (11, 13, 15). Ratios exceeding 3/4 have also been observed ratio of generation times around the Out-of-Africa bottleneck, and in most other hominids (ref. 14, but see ref. 21). that current diversity levels were affected by fairly recent changes These departures from 3/4 and differences among populations in sex-specific life history. and species have been attributed in part to the effects of demographic history, in particular to historical changes in population size. If we sex chromosomes | autosomes | polymorphism | life history | human Significance eutral polymorphism patterns on the X and autosomes re- Nflect a combination of evolutionary forces. Theory predicts All else being equal, the ratio of diversity levels on X and au- that, all else being equal, the ratio of diversity levels on X and tosomes at selectively neutral sites should mirror the ratio of autosomes at selectively neutral sites should mirror the ratio of their numbers in the population and thus equal 3/4. In reality, their numbers in the population and thus equal 3/4 (1). A the ratios observed across human populations differ markedly complication, however, is that autosomes spend an equal number from 3/4 and from each other. Because, from a population per- of generations in diploid form in both sexes, whereas the X spective, autosomes spend an equal number of generations in spends twice as many generations in diploid form in females as in both sexes, while the X spends twice as many generations in haploid form in males. As a result, the X-to-autosome (X:A) females, these departures from the naïve expectations plausibly diversity ratio can also be shaped by differences in male and reflect differences between male and female life histories and female life history and mutation processes, as well as by differ- their effects on mutation processes. Indeed, we show that the ences in the effects of demographic history and selection at ratios observed across human populations can be explained by linked sites on the X and autosomes. The effects of these factors demographic history, assuming realistic sex-specific mutation have been studied theoretically (2) and in relation to observa- rates, generation times, and reproductive variances. tions in many species (3–8). Notably, their effects on diversity ratios in human populations have attracted considerable interest Author contributions: G.A. and G.S. designed research; G.A. and G.S. performed research; over the past decade (9–15). G.A., D.A.M., and W.R.M. analyzed data; and G.A. and G.S. wrote the paper. The impact of selection at linked sites on neutral diversity The authors declare no competing interest. levels could differ for X and autosomes because of differences in This article is a PNAS Direct Submission. recombination rates, in the density of selected regions, and in the Published under the PNAS license. efficacy and modes of selection. Notably, the hemizygosity of the 1To whom correspondence may be addressed. Email: [email protected] or gs2747@ X in males leads to a more rapid fixation of partially or fully columbia.edu. recessive beneficial alleles and to a more rapid purging of recessive This article contains supporting information online at https://www.pnas.org/lookup/suppl/ deleterious ones (16, 17). Considering these effects and accounting doi:10.1073/pnas.1915664117/-/DCSupplemental. for recombination rates suggests that in humans—in mammals more First published August 3, 2020. www.pnas.org/cgi/doi/10.1073/pnas.1915664117 PNAS | August 18, 2020 | vol. 117 | no. 33 | 20063–20069 Downloaded by guest on September 27, 2021 assume that the effective population size of the X is generally smaller incorporates sex-specific reproductive variances and correlations than that of autosomes, then changes in population size will have a between the numbers of offspring at different ages. Generation different impact on diversity levels on X and autosomes (5, 22–24). times in females, GF, and in males, GM, are defined as the ex- Notably, population bottlenecks that occurred sufficiently recently, pectations of maternal and paternal ages at birth. Mutation rates such as the Out-of-Africa (OoA) bottleneck in human evolution, will can vary with sex and age, with their per-generation rates in fe- have decreased the X:A diversity ratio, because a greater proportion males, μF, and in males, μM, defined as expectations over parental of X-linked lineages will have coalesced during the bottleneck (24). ages. The expected number of offspring of each sex necessarily Indeed, simulation studies suggest that historical changes in pop- equals 1, but female and male reproductive variances, VF and VM, ulation size have contributed substantially to decreased X:A diversity respectively, may differ due to sex- and age-dependent mortality ratios with the distance from Africa (15). Historical differences be- and fecundity. tween males and females may have also played a role; for example, We show that the X:A ratio of effective population sizes (Ne), male-biased migration or longer male generation times during the defined as half the inverse of the coalescence rates, is OoA bottleneck may have also contributed to the lower X:A ratios in non-Africans (12). f(G =G ) NX NA = 3 · M F [1] Sex differences in life history traits are also likely to have had e / e , 4 f(γM VM +γF =γM ) substantial effects on X:A diversity ratios. The most straight- γF VF +γM =γF forward of these effects arises from sex differences in the vari- ance of offspring numbers, which, for brevity, we refer to as where f(x)=2x+4. We also show that the X:A ratio of expected “ ” 3x+3 reproductive variance. Higher reproductive variance in males diversity levels (i.e., heterozygosities) is than in females causes higher coalescence rates on autosomes and thus increases X:A diversity ratios (2, 9). This increase is E(πX ) 3 f(μM =μF) · f(GM =GF) theoretically bounded by a factor of 3=2 (2). Although probably = . [2] E(π ) γ V +γ =γ much lower in reality, a greater male reproductive variance is A 4 f( M M F M ) γF VF +γM =γF observed in extant hunter-gatherers and hominid species (25), indicating that it plausibly contributed to differences in X:A di- When the mutation rates, generation times, numbers of new- versity ratios among populations, as well as to their departure borns, and reproductive variance are identical in both sexes, the from 3=4.
Load more

Recommended publications
  • Alan Robert Templeton
    Alan Robert Templeton Charles Rebstock Professor of Biology Professor of Genetics & Biomedical Engineering Department of Biology, Campus Box 1137 Washington University St. Louis, Missouri 63130-4899, USA (phone 314-935-6868; fax 314-935-4432; e-mail [email protected]) EDUCATION A.B. (Zoology) Washington University 1969 M.A. (Statistics) University of Michigan 1972 Ph.D. (Human Genetics) University of Michigan 1972 PROFESSIONAL EXPERIENCE 1972-1974. Junior Fellow, Society of Fellows of the University of Michigan. 1974. Visiting Scholar, Department of Genetics, University of Hawaii. 1974-1977. Assistant Professor, Department of Zoology, University of Texas at Austin. 1976. Visiting Assistant Professor, Dept. de Biologia, Universidade de São Paulo, Brazil. 1977-1981. Associate Professor, Departments of Biology and Genetics, Washington University. 1981-present. Professor, Departments of Biology and Genetics, Washington University. 1983-1987. Genetics Study Section, NIH (also served as an ad hoc reviewer several times). 1984-1992: 1996-1997. Head, Evolutionary and Population Biology Program, Washington University. 1985. Visiting Professor, Department of Human Genetics, University of Michigan. 1986. Distinguished Visiting Scientist, Museum of Zoology, University of Michigan. 1986-present. Research Associate of the Missouri Botanical Garden. 1992. Elected Visiting Fellow, Merton College, University of Oxford, Oxford, United Kingdom. 2000. Visiting Professor, Technion Institute of Technology, Haifa, Israel 2001-present. Charles Rebstock Professor of Biology 2001-present. Professor of Biomedical Engineering, School of Engineering, Washington University 2002-present. Visiting Professor, Rappaport Institute, Medical School of the Technion, Israel. 2007-2010. Senior Research Associate, The Institute of Evolution, University of Haifa, Israel. 2009-present. Professor, Division of Statistical Genomics, Washington University 2010-present.
    [Show full text]
  • Human Evolution
    Note added by authors December 4, 2018: This study is grounded in and strongly supports Darwinian evolution, including the understanding that all life has evolved from a common biological origin over several billion years. This work follows mainstream views of human evolution. We do not propose there was a single "Adam" or "Eve". We do not propose any catastrophic events. HUMAN EVOLUTION Vol. 33 - n. 1-2 (1-30) - 2018 Stoeckle M.Y. Why should mitochondria define species? Program for the Human Environment The Rockefeller University 1230 York AVE More than a decade of DNA barcoding encompassing New York, NY 10065 about five million specimens covering 100,000 animal USA species supports the generalization that mitochondrial Email: [email protected] DNA clusters largely overlap with species as defined by domain experts. Most barcode clustering reflects synony- Thaler D.S. mous substitutions. What evolutionary mechanisms ac- Biozentrum, University of Basel count for synonymous clusters being largely coincident Klingelbergstrasse 50/70 with species? The answer depends on whether variants CH - 4056 Basel Switzerland are phenotypically neutral. To the degree that variants are Email: [email protected] selectable, purifying selection limits variation within spe- [email protected] cies and neighboring species may have distinct adaptive peaks. Phenotypically neutral variants are only subject to demographic processes—drift, lineage sorting, genetic DOI: 10.14673/HE2018121037 hitchhiking, and bottlenecks. The evolution of modern humans has been studied from several disciplines with detail unique among animal species. Mitochondrial bar- codes provide a commensurable way to compare modern humans to other animal species. Barcode variation in the modern human population is quantitatively similar to that within other animal species.
    [Show full text]
  • Sociobiology and Law
    Sociobiology and Law Allan Ardill LLB. (Hons), B.Bus. (Accounting), B.Bus. (HRM), A.Dip. Bus. (IR) A dissertation in fulfilment of the requirements for the degree of Doctor of Philosophy Griffith Law School Griffith University Gold Coast, Queensland, Australia. February 2008 2 Abstract The place of humans in nature and the nature of humans eludes us and yet there are those certain these issues can be reduced to biological explanations. Similarly, there are those rejecting the biological determinist hypothesis in favour of the equally unsubstantiated cultural construction hypothesis. This thesis draws on neo-Marxism and feminist intersectional post-positivist standpoint theory to posit biological and cultural determinism as privileged and flawed knowledge produced within relations of asymmetrical power. Instead “social construction” is preferred viewing knowledge of both nature and culture as partial and constructed within an historical, socioeconomic and political context according to asymmetrical power. Social constructionists prefer to question the role of power in the production of knowledge rather than asking questions about the place of humans in nature and the nature of humans; and trying to answer those questions through methods imbued with western, colonial, patriarchal, homophobic, and positivist ideals. As a starting point the postmodern view that knowledge is incomplete and has no ultimate authority is accepted. However, this thesis departs from postmodernism on the premise that knowledge is not all relative and can be critiqued by drawing on neo- Marxist and feminist intersectional post-positivist standpoint theory. Standpoint theory presumes a knowledge power nexus and contends accountable, ethical and responsible knowledge can be produced provided an “upwards perspective” is applied commencing with the standpoint of the most marginalised group within a given context.
    [Show full text]
  • The Evolution of Human Populations: a Molecular Perspective
    MOLECULAR PHYLOGENETICS AND EVOLUTION Vol. 5, No. 1, February, pp. 188±201, 1996 ARTICLE NO. 0013 The Evolution of Human Populations: A Molecular Perspective FRANCISCO J. AYALA AND ANANIAS A. ESCALANTE Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92717 Received August 2, 1995 ley, 1979, 1982). According to this theory, extreme Human evolution exhibits repeated speciations and population bottlenecks would facilitate speciation as conspicuous morphological change: from Australo- well as rapid morphological change. pithecus to Homo habilis, H. erectus, and H. sapiens; The human evolutionary line of descent for the last and from their hominoid ancestor to orangutans, goril- four million years (Myr) goes back from Homo sapiens las, chimpanzees, and humans. Theories of founder- to H. erectus, H. habilis, Australopithecus afarensis, event speciation propose that speciation often occurs and A. onamensis. Humans and chimpanzees shared as a consequence of population bottlenecks, down to a last common ancestor about six Myr ago; their last one or very few individual pairs. Proponents of punc- common ancestor with the gorillas lived somewhat ear- tuated equilibrium claim in addition that founder- lier; and the last common ancestor of humans, African event speciation results in rapid morphological apes, and orangutans lived some 15 Myr ago. The suc- change. The major histocompatibility complex (MHC) cession of hominid species from Australopithecus to H. consists of several very polymorphic gene loci. The ge- nealogy of 19 human alleles of the DQB1 locus co- sapiens occurred in association with some species split- alesces more than 30 million years ago, before the di- ting, as illustrated by such extinct lineages as Australo- vergence of apes and Old World monkeys.
    [Show full text]
  • The Context of Human Genetic Evolution Robert Foley1
    Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press PERSPECTIVE The Context of Human Genetic Evolution Robert Foley1 Human Evolutionary Biology Research Group, Department of Biological Anthropology, and King’s College Research Centre Human Diversity Project University of Cambridge, Cambridge, CB2 3DZ, UK The debate on modern human origins has often focused on the relationship between genes and fossils. Although more and more genetic evidence has been accumulating in favor of a recent African origin for modern humans, it has been assumed by many that the fossil evidence remains ambiguous. On the contrary, it has been clear for some time that the fossil evidence does not support the multiregional model: Fossils and archeology indicate a pattern of multiple dispersals from and beyond Africa, against which the genetic data can be compared. The continuing value of paleobiology is in complementing genetic information by revealing the context of human evolution: locating the dispersals and extinctions of populations in time and space, correlating these events with the environmental forces that shaped them, and providing an increasingly detailed understanding of the morphology and technology of early humans. Molecular biology has revolutionized the study of relatively small population (effective population human evolution. The importance of fossils as the size between 5000 and 50,000 individuals) (Rogers primary source of information about our past has and Harpending 1992; Harpending et al. 1993; Nei been steadily undermined as it has become possible and Takahata 1993; Harpending 1994). That size to infer detailed aspects of recent human history represents a bottleneck in the hominid lineage dat- from the distribution and frequency of genes found ing back no more than 200,000 years (Cann et al.
    [Show full text]
  • Abstracts for the ??Evolutionary Medicine Conference
    Ashdin Publishing Journal of Evolutionary Medicine ASHDIN Vol. 3 (2015), Article ID 235924, 45 pages publishing doi:10.4303/jem/235924 Abstracts CONFERENCE PROCEEDINGS Abstracts for the “Evolutionary Medicine Conference: Interdisciplinary Perspectives on Human Health and Disease” at the University of Zurich, Switzerland (July 30–August 1, 2015) Kaspar Staub,1 Nicole Bender,2 Paul Ewald,3 and Frank Ruhli¨ 1 1Institute of Evolutionary Medicine, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland 2Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland 3Department of Biology, University of Louisville, Louisville, KY 40292, USA Address correspondence to Frank Ruhli,¨ [email protected] Received 17 Aril 2015; Revised 11 May 2015; Accepted 14 May 2015 Copyright © 2015 Kaspar Staub et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Summary In summer 2015, the “Evolutionary Medicine Conference diseases. The discipline is now at a turning point at which a 2015: Interdisciplinary Perspectives on Human Health and Disease” rigorous application of evolutionary insights to the medical takes place at the Institute of Evolutionary Medicine, University of sciences will require not only assessing the validity of the Zurich, Switzerland. This international conference is the first of its kind in Europe and brings together eight distinguished keynote speak- full spectrum of possible explanations for each disease ers from all over the world as well as experts from different disci- but the interplay of different contributors to illness within plines (including medicine, anthropology, molecular/evolutionary biol- and between the three broad categories of causal factors: ogy, paleopathology, archeology, history, psychology, epidemiology, genetic, infectious, and environmental.
    [Show full text]
  • Contribution of Genetics in the Recent Human Evolution Study: Knowledge, Problems and Future Prospects
    Open Access Austin Journal of Genetics and Genomic A Austin Full Text Article Research Publishing Group Review Article Contribution of Genetics in the Recent Human Evolution Study: Knowledge, Problems and Future Prospects Hassen Chaabani* Abstract Laboratory of Human Genetics and Anthropology, University of Monastir, Tunisia The study of human evolution involves several scientific disciplines particularly paleontology, archeology and genetics. The research in the latter has *Corresponding author: Hassen Chaabani, provided new insights into the evolutionary relationships of human populations Laboratory of Human Genetics and Anthropology, leading to an improved understanding of their origin and their migration across University of Monastir, 5000 Monastir, Tunisia the globe. In fact, mutations on genes and non-coding DNA sequences occurred Received: June 20, 2014; Accepted: July 14, 2014; since our deep evolutionary past represent precious traces the analyses of Published: July 16, 2014 which permit to refer the past from present. The research development of human evolutionary genetic studies has been passed through two principal stages. In this paper I present briefly the most important general conclusions obtained during these two stages. Besides, I present and discuss emerged problems concerning particularly the persistence of some problematic considerations and confusions and vagueness related to some concepts. I believe that it is time to uproot all problematic considerations and resolve all other problems that have curbed the progression of research in this topic and to move on new more objective and more empirical research tracks. Keywords: Human evolutionary genetic studies; Protein markers; DNA markers; Research problems; Modern man origin; Questionable considerations; Research approaches Introduction and marked by the determination and use of DNA markers, has been developed mainly within a more specific new branch designated The subject of the origin of humans and their evolutionary history “Genetic Anthropology or Molecular Anthropology”.
    [Show full text]
  • A MUST-READ for HUMAN ETHOLOGISTS Darwin's Unfinished
    Richer, J.M. (2020). A must-read for Human Ethologists. Human Ethology, 35, Human Ethology 35 (2020): 27-31 27-31. https://doi.org/10.22330/he/35/027-031 Book Review A MUST-READ FOR HUMAN ETHOLOGISTS John M. Richer Department of Physiology, Anatomy and Genetics, University of Oxford, UK. Paediatric Psychology, Oxford University Hospitals NHS Trust, UK. [email protected] A Review of the Book Darwin's Unfinished Symphony. How Culture made the human mind By Kevin Laland . 2017. Princeton University Press. 464 pages. ISBN 9780691151182 (Hardback, $35.00, USD) __________________________________________________________________ All Human Ethologists should read this book. It is not that it is just well written but that the quality, style and creativity of thought behind it is an object lesson in how this area of science ought to be conducted. Darwin's unfinished symphony (of course a nod towards Franz Schubert), refers to his strong intimations that culture evolved just as did physical and behavioural characteristrics of animals. Laland, a thoroughgoing Zoologist, points out how human culture is so hugely different from anything in even primates or other large brained mammals and how this has had consequences for the success of our species, in particular in the way cultural knowledge cumulatively rachets up, it autocatalyses, such that "in the last 10-12 thousand years of cultural evolution, humanity has been to the moon, split the atom, built cities, complied encylopaedic knowledge, and composed symphonies."(page 235). By approaching the topic from a thoroughly zoological perspective and noting the uniqueness and strangeness of this complex, cumulative autocatalytic culture, he is able better to see the many factors, and what combination of factors, might be crucial to the evolution of human culture.
    [Show full text]
  • The Influence of Evolutionary History on Human Health and Disease
    REVIEWS The influence of evolutionary history on human health and disease Mary Lauren Benton 1,2, Abin Abraham3,4, Abigail L. LaBella 5, Patrick Abbot5, Antonis Rokas 1,3,5 and John A. Capra 1,5,6 ✉ Abstract | Nearly all genetic variants that influence disease risk have human-specific origins; however, the systems they influence have ancient roots that often trace back to evolutionary events long before the origin of humans. Here, we review how advances in our understanding of the genetic architectures of diseases, recent human evolution and deep evolutionary history can help explain how and why humans in modern environments become ill. Human populations exhibit differences in the prevalence of many common and rare genetic diseases. These differences are largely the result of the diverse environmental, cultural, demographic and genetic histories of modern human populations. Synthesizing our growing knowledge of evolutionary history with genetic medicine, while accounting for environmental and social factors, will help to achieve the promise of personalized genomics and realize the potential hidden in an individual’s DNA sequence to guide clinical decisions. In short, precision medicine is fundamentally evolutionary medicine, and integration of evolutionary perspectives into the clinic will support the realization of its full potential. Genetic disease is a necessary product of evolution These studies are radically changing our understanding (BOx 1). Fundamental biological systems, such as DNA of the genetic architecture of disease8. It is also now possi- replication, transcription and translation, evolved very ble to extract and sequence ancient DNA from remains early in the history of life. Although these ancient evo- of organisms that are thousands of years old, enabling 1Department of Biomedical lutionary innovations gave rise to cellular life, they also scientists to reconstruct the history of recent human Informatics, Vanderbilt created the potential for disease.
    [Show full text]
  • Genetics and Recent Human Evolution
    PERSPECTIVE doi:10.1111/j.1558-5646.2007.00164.x GENETICS AND RECENT HUMAN EVOLUTION Alan R. Templeton Department of Biology, Campus Box 1137, Washington University, St. Louis, Missouri 63130 E-mail: temple [email protected] Received January 12, 2007 Accepted April 19, 2007 Starting with “mitochondrial Eve” in 1987, genetics has played an increasingly important role in studies of the last two million years of human evolution. It initially appeared that genetic data resolved the basic models of recent human evolution in favor of the “out-of-Africa replacement” hypothesis in which anatomically modern humans evolved in Africa about 150,000 years ago, started to spread throughout the world about 100,000 years ago, and subsequently drove to complete genetic extinction (replacement) all other human populations in Eurasia. Unfortunately, many of the genetic studies on recent human evolution have suffered from scientific flaws, including misrepresenting the models of recent human evolution, focusing upon hypothesis compatibility rather than hypothesis testing, committing the ecological fallacy, and failing to consider a broader array of alternative hypotheses. Once these flaws are corrected, there is actually little genetic support for the out-of-Africa replacement hypothesis. Indeed, when genetic data are used in a hypothesis-testing framework, the out-of-Africa replacement hypothesis is strongly rejected. The model of recent human evolution that emerges from a statistical hypothesis-testing framework does not correspond to any of the traditional models of human evolution, but it is compatible with fossil and archaeological data. These studies also reveal that any one gene or DNA region captures only a small part of human evolutionary history, so multilocus studies are essential.
    [Show full text]
  • Understanding Rare and Common Diseases in the Context of Human Evolution Lluis Quintana-Murci1,2,3
    Quintana-Murci Genome Biology (2016) 17:225 DOI 10.1186/s13059-016-1093-y REVIEW Open Access Understanding rare and common diseases in the context of human evolution Lluis Quintana-Murci1,2,3 Abstract (e.g., migration, admixture, and changes in population size), and natural selection. The wealth of available genetic information is allowing The plethora of genetic information generated in the the reconstruction of human demographic and adaptive last ten years, thanks largely to the publication of se- history. Demography and purifying selection affect the quencing datasets for both modern human populations purge of rare, deleterious mutations from the human and ancient DNA samples [14–18], is making it possible population, whereas positive and balancing selection to reconstruct the genetic history of our species, and to can increase the frequency of advantageous variants, define the parameters characterizing human demographic improving survival and reproductioninspecific history: expansion out of Africa, the loss of genetic diversity environmental conditions. In this review, I discuss with increasing distance from Africa (i.e., the “serial founder how theoretical and empirical population genetics effect”), demographic expansions over different time scales, studies, using both modern and ancient DNA data, and admixture with ancient hominins [16–21]. These stud- are a powerful tool for obtaining new insight into ies are also revealing the extent to which selection has acted the genetic basis of severe disorders and complex on the human genome, providing insight into the way in disease phenotypes, rare and common, focusing which selection removes deleterious variation and the po- particularly on infectious disease risk. tential of human populations to adapt to the broad range of climatic, nutritional, and pathogenic environments they have occupied [22–28].
    [Show full text]
  • Recent Human Adaptation: Genomic Approaches, Interpretation and Insights
    REVIEWS Recent human adaptation: genomic approaches, interpretation and insights Laura B. Scheinfeldt1,2 and Sarah A. Tishkoff1,3 Abstract | The recent availability of genomic data has spurred many genome-wide studies of human adaptation in different populations worldwide. Such studies have provided insights into novel candidate genes and pathways that are putatively involved in adaptation to different environments, diets and disease prevalence. However, much work is needed to translate these results into candidate adaptive variants that are biologically interpretable. In this Review, we discuss methods that may help to identify true biological signals of selection and studies that incorporate complementary phenotypic and functional data. We conclude with recommendations for future studies that focus on opportunities to use integrative genomics methodologies in human adaptation studies. Reproductive fitness Evidence from the archaeological record as well as from polymorphism (SNP) and whole-genome sequencing A measure of how well an genetic and genomic studies demonstrates that anatomi- (WGS) data from many different populations, giving us organism survives and cally modern humans emerged in Africa ~200 thou- the ability to take a ‘top-down’ approach to the study of reproduces; it is generally sand years ago (kya) and rapidly migrated across the human adaptation in globally diverse populations. Thus, determined by the genetic contribution of an individual globe into new environments ~80–50 kya (reviewed studies of human adaptation have moved from focusing to the gene pool of the next in REFS 1,2). One of the implications of this history is on specific genes that are known to be involved in certain generation.
    [Show full text]