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      Genomics advances the study of inbreeding depression in the wild

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          Abstract

          Inbreeding depression (reduced fitness of individuals with related parents) has long been a major focus of ecology, evolution, and conservation biology. Despite decades of research, we still have a limited understanding of the strength, underlying genetic mechanisms, and demographic consequences of inbreeding depression in the wild. Studying inbreeding depression in natural populations has been hampered by the inability to precisely measure individual inbreeding. Fortunately, the rapidly increasing availability of high‐throughput sequencing data means it is now feasible to measure the inbreeding of any individual with high precision. Here, we review how genomic data are advancing our understanding of inbreeding depression in the wild. Recent results show that individual inbreeding and inbreeding depression can be measured more precisely with genomic data than via traditional pedigree analysis. Additionally, the availability of genomic data has made it possible to pinpoint loci with large effects contributing to inbreeding depression in wild populations, although this will continue to be a challenging task in many study systems due to low statistical power. Now that reliably measuring individual inbreeding is no longer a limitation, a major focus of future studies should be to more accurately quantify effects of inbreeding depression on population growth and viability.

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          Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon.

          Males and females share many traits that have a common genetic basis; however, selection on these traits often differs between the sexes, leading to sexual conflict. Under such sexual antagonism, theory predicts the evolution of genetic architectures that resolve this sexual conflict. Yet, despite intense theoretical and empirical interest, the specific loci underlying sexually antagonistic phenotypes have rarely been identified, limiting our understanding of how sexual conflict impacts genome evolution and the maintenance of genetic diversity. Here we identify a large effect locus controlling age at maturity in Atlantic salmon (Salmo salar), an important fitness trait in which selection favours earlier maturation in males than females, and show it is a clear example of sex-dependent dominance that reduces intralocus sexual conflict and maintains adaptive variation in wild populations. Using high-density single nucleotide polymorphism data across 57 wild populations and whole genome re-sequencing, we find that the vestigial-like family member 3 gene (VGLL3) exhibits sex-dependent dominance in salmon, promoting earlier and later maturation in males and females, respectively. VGLL3, an adiposity regulator associated with size and age at maturity in humans, explained 39% of phenotypic variation, an unexpectedly large proportion for what is usually considered a highly polygenic trait. Such large effects are predicted under balancing selection from either sexually antagonistic or spatially varying selection. Our results provide the first empirical example of dominance reversal allowing greater optimization of phenotypes within each sex, contributing to the resolution of sexual conflict in a major and widespread evolutionary trade-off between age and size at maturity. They also provide key empirical evidence for how variation in reproductive strategies can be maintained over large geographical scales. We anticipate these findings will have a substantial impact on population management in a range of harvested species where trends towards earlier maturation have been observed.
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            Genomic patterns of homozygosity in worldwide human populations.

            Genome-wide patterns of homozygosity runs and their variation across individuals provide a valuable and often untapped resource for studying human genetic diversity and evolutionary history. Using genotype data at 577,489 autosomal SNPs, we employed a likelihood-based approach to identify runs of homozygosity (ROH) in 1,839 individuals representing 64 worldwide populations, classifying them by length into three classes-short, intermediate, and long-with a model-based clustering algorithm. For each class, the number and total length of ROH per individual show considerable variation across individuals and populations. The total lengths of short and intermediate ROH per individual increase with the distance of a population from East Africa, in agreement with similar patterns previously observed for locus-wise homozygosity and linkage disequilibrium. By contrast, total lengths of long ROH show large interindividual variations that probably reflect recent inbreeding patterns, with higher values occurring more often in populations with known high frequencies of consanguineous unions. Across the genome, distributions of ROH are not uniform, and they have distinctive continental patterns. ROH frequencies across the genome are correlated with local genomic variables such as recombination rate, as well as with signals of recent positive selection. In addition, long ROH are more frequent in genomic regions harboring genes associated with autosomal-dominant diseases than in regions not implicated in Mendelian diseases. These results provide insight into the way in which homozygosity patterns are produced, and they generate baseline homozygosity patterns that can be used to aid homozygosity mapping of genes associated with recessive diseases. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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              Genomic Runs of Homozygosity Record Population History and Consanguinity

              The human genome is characterised by many runs of homozygous genotypes, where identical haplotypes were inherited from each parent. The length of each run is determined partly by the number of generations since the common ancestor: offspring of cousin marriages have long runs of homozygosity (ROH), while the numerous shorter tracts relate to shared ancestry tens and hundreds of generations ago. Human populations have experienced a wide range of demographic histories and hold diverse cultural attitudes to consanguinity. In a global population dataset, genome-wide analysis of long and shorter ROH allows categorisation of the mainly indigenous populations sampled here into four major groups in which the majority of the population are inferred to have: (a) recent parental relatedness (south and west Asians); (b) shared parental ancestry arising hundreds to thousands of years ago through long term isolation and restricted effective population size (Ne), but little recent inbreeding (Oceanians); (c) both ancient and recent parental relatedness (Native Americans); and (d) only the background level of shared ancestry relating to continental Ne (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan African agriculturalists), and the occasional cryptically inbred individual. Moreover, individuals can be positioned along axes representing this demographic historic space. Long runs of homozygosity are therefore a globally widespread and under-appreciated characteristic of our genomes, which record past consanguinity and population isolation and provide a distinctive record of the demographic history of an individual's ancestors. Individual ROH measures will also allow quantification of the disease risk arising from polygenic recessive effects.
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                Author and article information

                Contributors
                martykardos@gmail.com
                Journal
                Evol Appl
                Evol Appl
                10.1111/(ISSN)1752-4571
                EVA
                Evolutionary Applications
                John Wiley and Sons Inc. (Hoboken )
                1752-4571
                23 October 2016
                December 2016
                : 9
                : 10 ( doiID: 10.1111/eva.2016.9.issue-10 )
                : 1205-1218
                Affiliations
                [ 1 ] Department of Evolutionary Biology Evolutionary Biology CentreUppsala University UppsalaSweden
                [ 2 ] Department of AnatomyUniversity of Otago DunedinNew Zealand
                [ 3 ] Division of Biological SciencesUniversity of Montana Missoula MTUSA
                [ 4 ] Flathead Lake Biological Station Division of Biological SciencesUniversity of Montana Polson MTUSA
                Author notes
                [*] [* ] Correspondence

                Marty Kardos, Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.

                Email: martykardos@ 123456gmail.com

                Article
                EVA12414
                10.1111/eva.12414
                5108213
                27877200
                4b8d5b5c-a97a-47d2-8858-a1cbaf01d69c
                © 2016 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 April 2016
                : 05 August 2016
                Page count
                Figures: 3, Tables: 0, Pages: 14, Words: 12779
                Funding
                Funded by: Swedish Research Council
                Funded by: Knut and Alice Wallenberg Foundation
                Funded by: U.S. National Science Foundation
                Award ID: DEB‐1258203
                Categories
                Reviews and Syntheses
                Reviews and Syntheses
                Custom metadata
                2.0
                eva12414
                December 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.7 mode:remove_FC converted:14.11.2016

                Evolutionary Biology
                conservation genetics,fitness,identity by descent,pedigree analysis,whole‐genome resequencing

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