Seeing genes in space & time: the evolution of neutral and functional genetic diversity using woolly mammoth
Lead Research Organisation:
University of York
Department Name: Biology
Abstract
Understanding how a population changes through time is critical to understanding the broader picture of species evolution and extinction. By examining the dynamics of population change, we can explore how, as a result of changing competitive pressures and habitats, species distributions alter through time and space. Populations can increase or decline, or differ in their levels of migration and immigration. Although it is theoretically possible to directly observe these processes, the time span across which observations would be necessary renders this all but impractical. Fortunately, direct observation is not the only way to infer changes occurring in populations, because all of these processes leave traces in the genetic diversity of a species. By sequencing pieces of genetic information of a species (DNA) from a large number of individuals within a population, it is possible to shed light on the dynamics of species going back hundreds of thousands of years.
When analysing data from modern populations, data may be insufficient to acquire the full picture of past population change - any information from populations no longer around today will be lost. A far more powerful approach is to directly sample the genetics of past populations. This approach uses ancient DNA: DNA that survives trapped in tissue such as hair and bone dating back to ~120,000 years. Research in ancient DNA has shown that the dynamics of Pleistocene populations were more complicated than had been initially inferred from modern data alone. Critically, the Pleistocene is a period which covered a series of large changes in climate, and a detailed examination of Pleistocene population dynamics may shed light on how species respond to the effects of climate change.
However, there are difficulties arising from the decay of DNA over time, which leaves relatively few bones that can be successfully sampled, and results in short pieces of DNA, problematic for analyses. One upshot of this is that most ancient DNA studies to date have relied on an abundant, short loop of DNA called mitochondrial (mt) DNA. However, mtDNA is only passed down through the maternal line, and cannot provide any information on the paternal lineage. Sequencing a large number of dated bone samples for longer sequences of both mtDNA, and DNA from the cell nucleus, would shed light on both male and female evolutionary history, and provide a much better insight into how animal populations have changed over the last few hundred thousand years.
The woolly mammoth, an icon for both the Pleistocene and species extinction, is an ideal species in which to study how animals may be affected by climate and environmental change. Moreover, by examining genes that may be favoured during times of climate change, such as those involved in hair growth or cold adaptation, it will be possible to investigate any differing patterns in the DNA between these and more 'neutral' genes, helping us to better understand both the demographic and adaptive processes taking place in these populations.
Recent progress has made such a project possible. Using new high-throughput technologies for analysing DNA, in combination with methods to locate the specific DNA fragments of interest, we can now rapidly and efficiently analyse thousands of units of DNA code from hundreds of fossil remains, allowing us to infer what happened to populations in the past.
When analysing data from modern populations, data may be insufficient to acquire the full picture of past population change - any information from populations no longer around today will be lost. A far more powerful approach is to directly sample the genetics of past populations. This approach uses ancient DNA: DNA that survives trapped in tissue such as hair and bone dating back to ~120,000 years. Research in ancient DNA has shown that the dynamics of Pleistocene populations were more complicated than had been initially inferred from modern data alone. Critically, the Pleistocene is a period which covered a series of large changes in climate, and a detailed examination of Pleistocene population dynamics may shed light on how species respond to the effects of climate change.
However, there are difficulties arising from the decay of DNA over time, which leaves relatively few bones that can be successfully sampled, and results in short pieces of DNA, problematic for analyses. One upshot of this is that most ancient DNA studies to date have relied on an abundant, short loop of DNA called mitochondrial (mt) DNA. However, mtDNA is only passed down through the maternal line, and cannot provide any information on the paternal lineage. Sequencing a large number of dated bone samples for longer sequences of both mtDNA, and DNA from the cell nucleus, would shed light on both male and female evolutionary history, and provide a much better insight into how animal populations have changed over the last few hundred thousand years.
The woolly mammoth, an icon for both the Pleistocene and species extinction, is an ideal species in which to study how animals may be affected by climate and environmental change. Moreover, by examining genes that may be favoured during times of climate change, such as those involved in hair growth or cold adaptation, it will be possible to investigate any differing patterns in the DNA between these and more 'neutral' genes, helping us to better understand both the demographic and adaptive processes taking place in these populations.
Recent progress has made such a project possible. Using new high-throughput technologies for analysing DNA, in combination with methods to locate the specific DNA fragments of interest, we can now rapidly and efficiently analyse thousands of units of DNA code from hundreds of fossil remains, allowing us to infer what happened to populations in the past.
Planned Impact
The Potential Economic and Societal Impacts are outlined below; academic impacts are detailed in the Academic Beneficiaries document.
The Public. Supporting a better public understanding of biological evolution is of great importance for our society. The woolly mammoth as both an iconic species and an example of a species of tropical origin that evolutionarily adapted to a completely different environment, provides an excellent possibility to raise interest in evolutionary processes and demonstrate how evolution transforms species over time. The great public interest in mammoths will allow us to reach a broad public, starting from young children to adults of all age groups and educational backgrounds. We will directly engage the public by organizing talks with school children and giving public lectures as detailed in our Pathways to Impact plan and indirectly by writing a popular scientific article in a broadly disseminated magazine. Moreover, research on mammoth, especially genetic analyses as planned in our project, are generally met with great interest by the media and have previously figured heavily in a wide range of magazines, newspapers, online resources and television documentaries (e.g. National Geographic, Financial Times, BBC).
Conservation policy makers. Although gene flow is somewhat on the agenda of conservation policy makers as one factor contributing to the survival of threatened species, the long-term adaptive importance of gene flow is not yet well recognized. However, many Eurasian species have a large geographical distribution, with populations in different habitats likely having differential local adaptations. Therefore, especially during times of environmental change such as the upcoming human-induced climate change, migratory corridors that allow populations to exchange potentially adaptive alleles are likely to play an important role for the long-term survival of species. Showing the importance of such adaptive gene flow for species in the past will give policy makers strong arguments in favour of migratory corridors connecting otherwise isolated protected areas.
Education (schools and museums). Museums and schools will benefit from the research as our results will elucidate the genetic basis of evolution in a popular species. Our results will provide the basic scientific knowledge to better explain how animals adapt to environmental changes and how important it is for the long-term survival of species to have natural, viable populations that can exchange genes rather than only isolated small breeding groups in zoos. As such, our results will have the potential to feature in both museum exhibitions and schools material.
A better understanding of the long-term dynamics of different types of genetic markers as well as the importance of adaptive introgression in evolution will be important for researchers working in Evolutionary biology, Population ecology, Conservation biology and Quaternary science (see Academic Beneficiaries).
The Public. Supporting a better public understanding of biological evolution is of great importance for our society. The woolly mammoth as both an iconic species and an example of a species of tropical origin that evolutionarily adapted to a completely different environment, provides an excellent possibility to raise interest in evolutionary processes and demonstrate how evolution transforms species over time. The great public interest in mammoths will allow us to reach a broad public, starting from young children to adults of all age groups and educational backgrounds. We will directly engage the public by organizing talks with school children and giving public lectures as detailed in our Pathways to Impact plan and indirectly by writing a popular scientific article in a broadly disseminated magazine. Moreover, research on mammoth, especially genetic analyses as planned in our project, are generally met with great interest by the media and have previously figured heavily in a wide range of magazines, newspapers, online resources and television documentaries (e.g. National Geographic, Financial Times, BBC).
Conservation policy makers. Although gene flow is somewhat on the agenda of conservation policy makers as one factor contributing to the survival of threatened species, the long-term adaptive importance of gene flow is not yet well recognized. However, many Eurasian species have a large geographical distribution, with populations in different habitats likely having differential local adaptations. Therefore, especially during times of environmental change such as the upcoming human-induced climate change, migratory corridors that allow populations to exchange potentially adaptive alleles are likely to play an important role for the long-term survival of species. Showing the importance of such adaptive gene flow for species in the past will give policy makers strong arguments in favour of migratory corridors connecting otherwise isolated protected areas.
Education (schools and museums). Museums and schools will benefit from the research as our results will elucidate the genetic basis of evolution in a popular species. Our results will provide the basic scientific knowledge to better explain how animals adapt to environmental changes and how important it is for the long-term survival of species to have natural, viable populations that can exchange genes rather than only isolated small breeding groups in zoos. As such, our results will have the potential to feature in both museum exhibitions and schools material.
A better understanding of the long-term dynamics of different types of genetic markers as well as the importance of adaptive introgression in evolution will be important for researchers working in Evolutionary biology, Population ecology, Conservation biology and Quaternary science (see Academic Beneficiaries).
Publications
Brace S
(2016)
Evolutionary History of the Nesophontidae, the Last Unplaced Recent Mammal Family.
in Molecular biology and evolution
Campbell K
(2015)
Resurrecting phenotypes from ancient DNA sequences: promises and perspectives
in Canadian Journal of Zoology
Fortes GG
(2013)
Phenotypes from ancient DNA: approaches, insights and prospects.
in BioEssays : news and reviews in molecular, cellular and developmental biology
Hofreiter M
(2015)
The future of ancient DNA: Technical advances and conceptual shifts.
in BioEssays : news and reviews in molecular, cellular and developmental biology
Palkopoulou E
(2013)
Holarctic genetic structure and range dynamics in the woolly mammoth.
in Proceedings. Biological sciences
Shapiro B
(2014)
A paleogenomic perspective on evolution and gene function: new insights from ancient DNA.
in Science (New York, N.Y.)
Springer MS
(2015)
Interordinal gene capture, the phylogenetic position of Steller's sea cow based on molecular and morphological data, and the macroevolutionary history of Sirenia.
in Molecular phylogenetics and evolution
Welker F
(2015)
Ancient proteins resolve the evolutionary history of Darwin's South American ungulates.
in Nature
| Description | Preliminary sequencing of woolly mammoth (Mammuthus primigenius) samples indicated six individuals with high endogenous content suitable for whole genome sequencing. This result is particularly exciting since it includes two European mammoths (including one from Scotland) - a group which went extinct in Europe around 33kya, and for which no genomic sequences whatsoever are available so far. The data we have obtained and are currently analysing will allow us to find out whether the European individuals are a separate early diverging clade of mammoths to the Siberian/American mammoths (for which some genomic data are available) as the mitochondrial data suggests, or whether they are simply a maternal lineage that disappeared locally as genomic data (suggested to be the case for a distinct mitochondrial clade of Siberian mammoths, also once speculated to be a separate early diverging clade or even species of mammoths). The possibility that there could be a separate divergent lineage of European mammoths, which is also found in the UK, is not widely known outside the scientific community and has the potential to result in high impact publications. It is also possible that the picture in mammoths is similar to that in humans in Neanderthals with a temporary population separation followed by secondary gene flow. Whatever the final answer will be, our data that are currently in the bioinformatic analysis pipeline will fill the European gap in the evolutionary history of the woolly mammoth. Finally, for megafauna species other than humans, palaeogenomic data have so far been obtained only from permafrost specimens, therefore obtaining genomic data from European mammoths also represents a conceptual and technical progress in palaeobiological research. In addition to our whole genome shotgun sequencing, we have designed RNA capture baits using the published Loxodonta genome, to target approximately 140 functional genes and 1000 x 1000bp neutral ancient nuclear sequences for ~50 mammoths. This cross-species nuclear capture is proof of concept research, which will have considerable impact for the scientific community, as it opens up a wealth of opportunities to target extinct and extant museum specimens, for which published genomes are missing, or hard to obtain. The high through-put element (50 samples) is also important, because a whole population genomic project can be designed and executed from a collection of non-invasively sampled museum specimens, and should provide sufficient data, even if many do not yield considerable DNA. Again, beyond the technical and conceptual advance, the data obtained and currently analysed represent the first palaeo-population genomic data obtained using a targeted approach for a species other than humans. In this respect, the project is at the cutting edge of palaeogenomic research. Finally we have used DNA baits to capture the mitochondrial genomes of ~100 species. This is the largest-to-date dataset of mammoth mitogenomes, which will complement our nuclear datasets and hopefully enable us to examine the evolutionary history of both the male and female mammoth line. Taken altogether, the population genomic analysis of these datasets have potentially wide ranging impacts: greatly contributing to our understanding of the extinction process, enabling us to better conserve endangered species, improving our understanding of changes in population genetic diversity over time (ancient samples providing more detail than only extant taxa), as well as highlighting the importance of population genomics data in the de-extinction debate. Updated findings: 1) In total, we applied mitochondrial hybridization capture on a large set of mammoth samples, totaling 89 individuals. For the majority of these samples (~75 individuals), we were able to reconstruct the complete mitochondrial genome with high average coverage between 20x and 1150x. This dataset significantly increases our knowledge of mammoth maternal diversity. Moreover, excitingly, three of these samples date from the Late Middle Pleistocene between 100-200kya (outside the realms of 14C dating), representing the first Middle Pleistocene DNA data for mammoth and doubling the total number of Middle Pleistocene fossils from which ancient DNA has been obtained so far. These sequences will shed light on the evolutionary history of mammoths beyond the previous glacial maximum (> 130 kya). By combining these data with published data sets, we will be able to provide a complete picture of the maternal history of mammoth, including part of the population dynamics beyond the Eemian interglacial. 2) We also applied hybridization capture for nuclear loci on 47 samples. The coverage of the nuclear capture is expectedly not as high as the mitochondrial capture. However, since we know the library DNA concentration for all investigated samples, the data we obtained provides unique information regarding the concentration of DNA required to make nuclear capture work at different levels. Moreover, when combined with published shotgun sequencing data and those of the high endogenous samples (see under 3) we will be able to provide, for the first time, a nuclear DNA population data set for an extinct species. The analyses of these data are currently running. 3) For a full analysis of the data that we have obtained from the nuclear capture, we will have to wait until the whole genome analysis of the 6 best preserved samples for which we obtained shotgun genome data is finished. These data will also allow us, for the first time to examine questions regarding the nuclear DNA relationships of the three mammoth mitogenome clades. The six nuclear genomes which have been sequenced are currently being mapped to the most recent release of the Loxodonta genome. Together with the nuclear capture data, these data will provide a comprehensive view on the nuclear evolutionary history of the woolly mammoth. |
| Exploitation Route | The cross-species nuclear capture is proof of concept research, which will have considerable impact for the scientific community, as it opens up a wealth of opportunities to target extinct and extant museum specimens, for which published genomes are missing, or hard to obtain. The population genomic analyses enable us to better conserve endangered species |
| Sectors | Environment,Culture, Heritage, Museums and Collections |
| Description | The possibility that there could be a separate divergent lineage of European mammoths, which is also found in the UK, is not widely known outside the scientific community and has the potential to result in publicity in the mainstream press, increasing the profile of both mammoths and palaeo-genomic research in the public eye. This has knock on positive effects for economic factors such as museum attendance and inspiring young people to go in to science. The life sciences sector remains crucial to the UK economy and works collaboratively, with newly emerging methods and research shared across disciplines. This project is pioneering new techniques in cross-species DNA capture and population genomics. Such techniques may have important uses in other areas of the biological sciences such as conservation or biomedical/health research. Novel biological methods are regularly taken up by biomedical researchers in both the public and private sectors. |
| First Year Of Impact | 2015 |
| Sector | Environment,Healthcare,Culture, Heritage, Museums and Collections |