Leveraging a natural murine meiotic drive to suppress invasive populations.

Invasive rodents are a major cause of environmental damage and biodiversity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate a gene drive strategy (tCRISPR) that leverages super-Mendelian transmission of the t haplotype to spread inactivating mutations in a haplosufficient female fertility gene (Prl). Using spatially explicit individual-based in silico modeling, we show that tCRISPR can eradicate island populations under a range of realistic field-based parameter values. We also engineer transgenic tCRISPR mice that, crucially, exhibit biased transmission of the modified t haplotype and Prl mutations at levels our modeling predicts would be sufficient for eradication. This is an example of a feasible gene drive system for invasive alien rodent population control.

Gene drives for vertebrate pest control: Realistic spatial modelling of eradication probabilities and times for island mouse populations.

Invasive alien species continue to threaten global biodiversity. CRISPR-based gene drives, which can theoretically spread through populations despite imparting a fitness cost, could be used to suppress or eradicate pest populations. We develop an individual-based, spatially explicit, stochastic model to simulate the ability of CRISPR-based homing and X chromosome shredding drives to eradicate populations of invasive house mice (Mus muculus) from islands. Using the model, we explore the interactive effect of the efficiency of the drive constructs and the spatial ecology of the target population on the outcome of a gene-drive release. We also consider the impact of polyandrous mating and sperm competition, which could compromise the efficacy of some gene-drive strategies. Our results show that both drive strategies could be used to eradicate large populations of mice. Whereas parameters related to drive efficiency and demography strongly influence drive performance, we find that sperm competition following polyandrous mating is unlikely to impact the outcome of an eradication effort substantially. Assumptions regarding the spatial ecology of mice influenced the probability of and time required for eradication, with short-range dispersal capacities and limited mate-search areas producing 'chase' dynamics across the island characterized by cycles of local extinction and recolonization by mice. We also show that highly efficient drives are not always optimal, when dispersal and mate-search capabilities are low. Rapid local population suppression around the introduction sites can cause loss of the gene drive before it can spread to the entire island. We conclude that, although the design of efficient gene drives is undoubtedly critical, accurate data on the spatial ecology of target species are critical for predicting the result of a gene-drive release.

Archaeogenetics of Late Iron Age Çemialo Sirti, Batman: Investigating maternal genetic continuity in north Mesopotamia since the Neolithic.

OBJECTIVES: North Mesopotamia has witnessed dramatic social change during the Holocene, but the impact of these events on its demographic history is poorly understood. Here, we study this question by analysing genetic data from the recently excavated Late Iron Age settlement of Çemialo Sirti in Batman, southeast Turkey. Archaeological and radiocarbon evidence indicate that the site was inhabited during the second and first millennia BCE. Çemialo Sirti reveals nomadic items of the Early Iron Age, as well as items associated with the Late Achaemenid and subsequent Hellenistic Periods. We compare Çemialo Sirti mitochondrial DNA profiles with earlier and later populations from west Eurasia to describe genetic continuity patterns in the region. MATERIALS AND METHODS: A total of 16 Çemialo Sirti individuals' remains were studied. PCR and Sanger sequencing were used to obtain mitochondrial DNA HVRI-HVRII sequences. We studied haplotype diversity and pairwise genetic distances using FST , comparing the Çemialo Sirti population with ancient and modern-day populations from west Eurasia. Coalescent simulations were carried out to test continuity for specific population comparisons. RESULTS: Mitochondrial DNA (mtDNA) haplotypes from 12 Çemialo Sirti individuals reveal high haplotype diversity in this population, conspicuously higher than early Holocene west Eurasian populations, which supports the notion of increasing population admixture in west Eurasia through the Holocene. In its mtDNA composition, Çemialo Sirti shows highest affinity to Neolithic north Syria and Neolithic Anatolia among ancient populations studied, and to modern-day southwest Asian populations. Based on population genetic simulations we cannot reject continuity between Neolithic and Iron Age, or between Iron Age and present-day populations of the region. DISCUSSION: Despite the region's complex sociopolitical history and indication for increased genetic diversity over time, we find no evidence for sharp shifts in north Mesopotamian maternal genetic composition within the last 10,000 years.

Patterns of species ranges, speciation, and extinction.

The exact nature of the relationship among species range sizes, speciation, and extinction events is not well understood. The factors that promote larger ranges, such as broad niche widths and high dispersal abilities, could increase the likelihood of encountering new habitats but also prevent local adaptation due to high gene flow. Similarly, low dispersal abilities or narrower niche widths could cause populations to be isolated, but such populations may lack advantageous mutations due to low population sizes. Here we present a large-scale, spatially explicit, individual-based model addressing the relationships between species ranges, speciation, and extinction. We followed the evolutionary dynamics of hundreds of thousands of diploid individuals for 200,000 generations. Individuals adapted to multiple resources and formed ecological species in a multidimensional trait space. These species varied in niche widths, and we observed the coexistence of generalists and specialists on a few resources. Our model shows that species ranges correlate with dispersal abilities but do not change with the strength of fitness trade-offs; however, high dispersal abilities and low resource utilization costs, which favored broad niche widths, have a strong negative effect on speciation rates. An unexpected result of our model is the strong effect of underlying resource distributions on speciation: in highly fragmented landscapes, speciation rates are reduced.