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Using time serial samples to characterize the timing ad strength of selective sweeps

English title Using time serial samples to characterize the timing ad strength of selective sweeps
Applicant Malaspinas Anna Sapfo
Number 143529
Funding scheme Fellowships for prospective researchers
Research institution Natural History Museum of Denmark University of Copenhagen
Institution of higher education Institution abroad - IACH
Main discipline Genetics
Start/End 01.09.2012 - 31.10.2014
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All Disciplines (2)

Discipline
Genetics
Molecular Biology

Keywords (1)

evolution, ancient DNA, adaptation, demography

Lay Summary (English)

Lead
Lay summary

BACKGROUND: The field of ancient DNA has recently entered the genomics era, with several whole nuclear genomes available. It is now possible to address fundamental evolutionary questions utilizing the temporal aspect of this new data, such as the amount of selection acting on the genome. However, methods to analyze ancient DNA are lacking owing to the previous rarity of this data type.

AIMS: The main goals of my proposal are to 1) develop methods tailored to the characteristics of ancient DNA, in particular the time serial aspect 2) apply those methods to answer biological relevant such as the adaptation to high altitude in the Andes. The goal is to identify regions in the genome that are under selection for high altitude adaptation.

METHODOLOGY: Methods: We will build on existing methods based on diffusion approximation to classical population genetics models. Extensions will include application of the one locus theory to whole genome data taking a likelihood approach, and usage of the linkage information.

Data:  We will sequence exomes for 15 mummy samples from the Andes in order to characterize the strength and timing of selective events associated with adaptation to high altitude on the Altiplano.

We expect to learn more about unique processes such as how and when humans adapted to high altitude.
POTENTIAL RESULTS:


Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Publications

Publication
bammds: a tool for assessing the ancestry of low-depth whole-genome data using multidimensional scaling (MDS).
Malaspinas Anna-Sapfo, Tange Ole, Moreno-Mayar José Víctor, Rasmussen Morten, DeGiorgio Michael, Wang Yong, Valdiosera Cristina E, Politis Gustavo, Willerslev Eske, Nielsen Rasmus (2014), bammds: a tool for assessing the ancestry of low-depth whole-genome data using multidimensional scaling (MDS)., in Bioinformatics (Oxford, England), 30(20), 2962-4.
Genome-wide Ancestry Patterns in Rapanui Suggest Pre-European Admixture with Native Americans
Moreno-Mayar J. Víctor, Rasmussen Simon, Seguin-Orlando Andaine, Rasmussen Morten, Liang Mason, Flåm Siri Tennebø, Lie Benedicte Alexandra, Gilfillan Gregor Duncan, Nielsen Rasmus, Thorsby Erik, Willerslev Eske, Malaspinas Anna-Sapfo (2014), Genome-wide Ancestry Patterns in Rapanui Suggest Pre-European Admixture with Native Americans, in Current Biology, 24(21), 2518-2525.
Genomic structure in Europeans dating back at least 36,200 years
Seguin-Orlando Andaine, Korneliussen Thorfinn S., Sikora Martin, Malaspinas Anna-Sapfo, Manica Andrea, Moltke Ida, Albrechtsen Anders, Ko Amy, Margaryan Ashot, Moiseyev Vyacheslav, Goebel Ted, Westaway Michael, Lambert David, Khartanovich Valeri, Wall Jeffrey D., Nigst Philip R., Foley Robert A., Lahr Marta Mirazon, Nielsen Rasmus, Orlando Ludovic, Willerslev Eske (2014), Genomic structure in Europeans dating back at least 36,200 years, in SCIENCE, 346(6213), 1113-1118.
Influenza virus drug resistance: a time-sampled population genetics perspective.
Foll Matthieu, Poh Yu-Ping, Renzette Nicholas, Ferrer-Admetlla Anna, Bank Claudia, Shim Hyunjin, Malaspinas Anna-Sapfo, Ewing Gregory, Liu Ping, Wegmann Daniel, Caffrey Daniel R, Zeldovich Konstantin B, Bolon Daniel N, Wang Jennifer P, Kowalik Timothy F, Schiffer Celia A, Finberg Robert W, Jensen Jeffrey D (2014), Influenza virus drug resistance: a time-sampled population genetics perspective., in PLoS genetics, 10(2), 1004185-1004185.
The genetic prehistory of the New World Arctic.
Raghavan Maanasa, DeGiorgio Michael, Albrechtsen Anders, Moltke Ida, Skoglund Pontus, Korneliussen Thorfinn S, Grønnow Bjarne, Appelt Martin, Gulløv Hans Christian, Friesen T Max, Fitzhugh William, Malmström Helena, Rasmussen Simon, Olsen Jesper, Melchior Linea, Fuller Benjamin T, Fahrni Simon M, Stafford Thomas, Grimes Vaughan, Renouf M A Priscilla, Cybulski Jerome, Lynnerup Niels, Lahr Marta Mirazon, Britton Kate, Knecht Rick (2014), The genetic prehistory of the New World Arctic., in Science (New York, N.Y.), 345(6200), 1255832-1255832.
The genome of a Late Pleistocene human from a Clovis burial site in western Montana.
Rasmussen Morten, Anzick Sarah L, Waters Michael R, Skoglund Pontus, DeGiorgio Michael, Stafford Thomas W, Rasmussen Simon, Moltke Ida, Albrechtsen Anders, Doyle Shane M, Poznik G David, Gudmundsdottir Valborg, Yadav Rachita, Malaspinas Anna-Sapfo, White Samuel Stockton, Allentoft Morten E, Cornejo Omar E, Tambets Kristiina, Eriksson Anders, Heintzman Peter D, Karmin Monika, Korneliussen Thorfinn Sand, Meltzer David J, Pierre Tracey L, Stenderup Jesper (2014), The genome of a Late Pleistocene human from a Clovis burial site in western Montana., in Nature, 506(7487), 225-9.
Two ancient human genomes reveal Polynesian ancestry among the indigenous Botocudos of Brazil
Malaspinas Anna-Sapfo, Lao Oscar, Schroeder Hannes, Rasmussen Morten, Raghavan Maanasa, Moltke Ida, Campos Paula F., Sagredo Francisca Santana, Rasmussen Simon, Gonçalves Vanessa F., Albrechtsen Anders, Allentoft Morten E., Johnson Philip L. F., Li Mingkun, Reis Silvia, Bernardo Danilo V., DeGiorgio Michael, Duggan Ana T., Bastos Murilo, Wang Yong, Stenderup Jesper, Moreno-Mayar J. Victor, Brunak Søren, Sicheritz-Ponten Thomas, Hodges Emily (2014), Two ancient human genomes reveal Polynesian ancestry among the indigenous Botocudos of Brazil, in Current Biology, 24(21), 1035-1037.
Identification of Polynesian mtDNA haplogroups in remains of Botocudo Amerindians from Brazil.
Gonçalves Vanessa Faria, Stenderup Jesper, Rodrigues-Carvalho Cláudia, Silva Hilton P, Gonçalves-Dornelas Higgor, Líryo Andersen, Kivisild Toomas, Malaspinas Anna-Sapfo, Campos Paula F, Rasmussen Morten, Willerslev Eske, Pena Sergio Danilo J (2013), Identification of Polynesian mtDNA haplogroups in remains of Botocudo Amerindians from Brazil., in Proceedings of the National Academy of Sciences of the United States of America, 110(16), 6465-9.
Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse.
Orlando Ludovic, Ginolhac Aurélien, Zhang Guojie, Froese Duane, Albrechtsen Anders, Stiller Mathias, Schubert Mikkel, Cappellini Enrico, Petersen Bent, Moltke Ida, Johnson Philip L F, Fumagalli Matteo, Vilstrup Julia T, Raghavan Maanasa, Korneliussen Thorfinn, Malaspinas Anna-Sapfo, Vogt Josef, Szklarczyk Damian, Kelstrup Christian D, Vinther Jakob, Dolocan Andrei, Stenderup Jesper, Velazquez Amhed M V, Cahill James, Rasmussen Morten (2013), Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse., in Nature, 499(7456), 74-8.

Abstract

BACKGROUND:The field of ancient DNA has recently entered the genomics era, with several available whole nuclear genomes. Thus, it is now possible to address fundamental evolutionary questions utilizing ancient DNA, and there is particular interest in the possibility of further quantifying the tempo and mode of positive selection. However, there exist a paucity of methods for analyzing ancient DNA, and the uniquely valuable time-serial aspect of such data is often disregarded.AIMS:The goals of my proposal are to 1) develop methods tailored to the characteristics of ancient DNA, and 2) apply those methods to answer biologically relevant questions related to the adaptation to high altitude in the Andes and the domestication of modern horses. The proposed methods aim to detect regions of the genome under positive selection, and specifically to identify genomic regions underlying phenotypic adaptations particular to these two examples.METHODOLOGY:Methods:Building upon existing methodology based on diffusion approximation to classical population genetics models, our first aim will be to extend one-locus theory to whole genomes, taking a likelihood approach. The second and third extensions will involve the utilization of linkage information and a relaxation of the assumptions governing the strength of selection, respectively. Data:The developed methodology, though anticipated to be widely applicable across the field, will be highlighted in two illustrative applications herein:1)whole nuclear genomes from pre- and post-domesticated horses - allowing for the identification of regions important in the process of domestication2)sequenced exomes from 15 mummy samples from the Andes - in order to characterize the selective sweeps associated with adaptation to high altitude on the Altiplano.RELEVANCE:Our findings will have relevance in several related areas. The methods will benefit the ancient DNA community, but also fields such as experimental evolution and epidemiology where data is collected at several time points. In order to facilitate this exchange - all developed code and methodology will be hosted from the lab website, with extensive documentation. The biological applications will be of general importance as well, both to 1) understand how the domestication process is reflected in the genome of modern horse, but also to understand the genetics of artificial selection induced via domestication in general, and 2) will have applications to medicine given the similar physiological challenges at high altitude and those stresses generated by a heart or lung failure.
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