Periodic Reporting for period 2 - ARCHAIC ADAPT (Admixture accelerated adaptation: signals from modern, ancient and archaic DNA.)
Periodo di rendicontazione: 2022-06-01 al 2023-11-30
Interbreeding with Neanderthals and Denisovans in the past introduced archaic DNA into modern human populations, an event often referred to as archaic introgression. Having access to Neanderthal and Denisovan genomes has enabled the quantification of the amount of archaic DNA present in individuals today, ranging from 0.1% to 7%. In my lab, we have discovered that some of this DNA has been useful in facilitating adaptations to diverse environments, which likely contributed to the expansion of humans into Europe, Asia, Oceania and the Americas. While there are some examples of how positive natural selection acted on archaic alleles, we still lack the full picture of how archaic variation evolved in modern human populations.
In this project, we will leverage the genomes of ancient humans spanning a wide geographical and temporal range to characterize how archaic variants have evolved over time and space in distinct modern human populations. This work also involves developing and benchmarking new methods to detect archaic ancestry in ancient genomes. By applying new methods and approaches to both ancient and modern genomic data sets, our analyses will provide a deeper understanding of the trajectories of archaic alleles over time. We will be able to determine what alleles have been purged, retained, and which ones have increased in frequency in the population. By looking at time-transects, we should also be able to observe the effects of population turnovers that have occurred in the history of modern humans. Moreover, examining the fragments of archaic DNA over time will enable inference of the timing of introgression and the timing of natural selection. Having this information will resolve details on the evolutionary processes that have affected the evolution of surviving archaic alleles. Our results will be important for determining the impact of archaic introgression in human evolution
In this project, we will leverage the genomes of ancient humans spanning a wide geographical and temporal range to characterize how archaic variants have evolved over time and space in distinct modern human populations. This work also involves developing and benchmarking new methods to detect archaic ancestry in ancient genomes. By applying new methods and approaches to both ancient and modern genomic data sets, our analyses will provide a deeper understanding of the trajectories of archaic alleles over time. We will be able to determine what alleles have been purged, retained, and which ones have increased in frequency in the population. By looking at time-transects, we should also be able to observe the effects of population turnovers that have occurred in the history of modern humans. Moreover, examining the fragments of archaic DNA over time will enable inference of the timing of introgression and the timing of natural selection. Having this information will resolve details on the evolutionary processes that have affected the evolution of surviving archaic alleles. Our results will be important for determining the impact of archaic introgression in human evolution
During this reporting period, we wanted to investigate the following questions:
(1) What is the underlying model of positive natural selection acting on cases of adaptive introgression; was archaic variation immediately beneficial or does natural selection act later on standing archaic variation?
(2) What is the landscape of Neanderthal and Denisovan ancestry as a function of time and space?
(3) Are there any signatures of positive natural selection associated with the different time periods in modern human history in Europe?
To address the first question we aim to infer when natural positive selection acted on Neanderthal archaic variation in Europeans and East Asians using data from present-day human genomes. From present-day genomes we curated a list of genes that have signatures of both introgression (from Neanderthals) and positive selection in Europeans and East Asians, and we then use the archaic alleles present in these genes to ask about the process of natural selection. Using a model that incorporates both the evolutionary effects of natural selection and admixture from Neanderthals, our preliminary results suggest that most cases of natural selection acted soon after the introgression event. This makes sense, as expanding human populations had to adapt quickly to the new environments of Eurasia.
We also want to incorporate data from the past. To this end, in our lab we are helping impute around 2000 ancient genomes from Eurasian populations as a data resource to help us address our questions, but also as a resource for the community. We have been benchmarking these data to ensure that we can recapitulate results from the un-imputed data with the imputed data. As of today, we have imputed a set of over 1500 ancient genomes that we are utilizing to characterize the landscape of Neanderthal and Denisovan introgression over time and space (question 2). In particular, we will be able to follow the evolution of archaic introgression during the Paleolithic, Mesolithic, Neolithic, Bronze age and Iron age. With these data, we will be able to track ancestry in different time periods and the evolutionary histories of adaptively introgressed loci in Europe as we can observe changes in allele frequency across time.
(1) What is the underlying model of positive natural selection acting on cases of adaptive introgression; was archaic variation immediately beneficial or does natural selection act later on standing archaic variation?
(2) What is the landscape of Neanderthal and Denisovan ancestry as a function of time and space?
(3) Are there any signatures of positive natural selection associated with the different time periods in modern human history in Europe?
To address the first question we aim to infer when natural positive selection acted on Neanderthal archaic variation in Europeans and East Asians using data from present-day human genomes. From present-day genomes we curated a list of genes that have signatures of both introgression (from Neanderthals) and positive selection in Europeans and East Asians, and we then use the archaic alleles present in these genes to ask about the process of natural selection. Using a model that incorporates both the evolutionary effects of natural selection and admixture from Neanderthals, our preliminary results suggest that most cases of natural selection acted soon after the introgression event. This makes sense, as expanding human populations had to adapt quickly to the new environments of Eurasia.
We also want to incorporate data from the past. To this end, in our lab we are helping impute around 2000 ancient genomes from Eurasian populations as a data resource to help us address our questions, but also as a resource for the community. We have been benchmarking these data to ensure that we can recapitulate results from the un-imputed data with the imputed data. As of today, we have imputed a set of over 1500 ancient genomes that we are utilizing to characterize the landscape of Neanderthal and Denisovan introgression over time and space (question 2). In particular, we will be able to follow the evolution of archaic introgression during the Paleolithic, Mesolithic, Neolithic, Bronze age and Iron age. With these data, we will be able to track ancestry in different time periods and the evolutionary histories of adaptively introgressed loci in Europe as we can observe changes in allele frequency across time.
We expect to see some changes in the amount of archaic ancestry associated with some of the known populations replacements that occurred in Europe.
Our results will provide insight into what is the role of archaic variation in modern humans populations.
Our results will provide insight into what is the role of archaic variation in modern humans populations.