Biomedical subjects
Andrea Manica
Publications and source records attributed to Andrea Manica.
A geographically explicit genetic model of worldwide human-settlement history.
Currently available genetic and archaeological evidence is generally interpreted as supportive of a recent single origin of modern humans in East Africa. However, this is where the near consensus on human settlement history ends, and considerable uncertainty clouds any more detailed aspect of human colonization history. Here, we present a dynamic genetic model of human settlement history coupled with explicit geographical distances from East Africa, the likely origin of modern humans. We search for the best-supported parameter space by fitting our analytical prediction to genetic data that are based on 52 human populations analyzed at 783 autosomal microsatellite markers. This framework allows us to jointly estimate the key parameters of the expansion of modern humans. Our best estimates suggest an initial expansion of modern humans approximately 56,000 years ago from a small founding population of approximately 1,000 effective individuals. Our model further points to high growth rates in newly colonized habitats. The general fit of the model with the data is excellent. This suggests that coupling analytical genetic models with explicit demography and geography provides a powerful tool for making inferences on human-settlement history.
Global genetic positioning: evidence for early human population centers in coastal habitats.
For an alternative perspective on relationships among human populations, we combined genetic and geographic information, using allele frequency gradients to place populations and individuals on the globe. Reanalyzing published data on 51 worldwide populations [Rosenberg, N. A., Pritchard, J. K., Weber, J. L., Cann, H. M., Kidd, K. K., Zhivitovsky, L. A. & Feldman, M. W. (2002) Science 298, 2381-2385] reveals five geographic clusters lying in plausible sites either of early agricultural innovation or on ancient migration routes. Also, the inferred sites show significant association with coastlines, suggesting that most early humans lived near large bodies of water. Our approach is flexible, and developments should prove useful both for exploring historical demography and for the identification of likely origin for unknown forensic samples.
Effects of sampling regime on the mean and variance of home range size estimates.
1. Although the home range is a fundamental ecological concept, there is considerable debate over how it is best measured. There is a substantial literature concerning the precision and accuracy of all commonly used home range estimation methods; however, there has been considerably less work concerning how estimates vary with sampling regime, and how this affects statistical inferences. 2. We propose a new procedure, based on a variance components analysis using generalized mixed effects models to examine how estimates vary with sampling regime. 3. To demonstrate the method we analyse data from one study of 32 individually marked roe deer and another study of 21 individually marked kestrels. We subsampled these data to simulate increasingly less intense sampling regimes, and compared the performance of two kernel density estimation (KDE) methods, of the minimum convex polygon (MCP) and of the bivariate ellipse methods. 4. Variation between individuals and study areas contributed most to the total variance in home range size. Contrary to recent concerns over reliability, both KDE methods were remarkably efficient, robust and unbiased: 10 fixes per month, if collected over a standardized number of days, were sufficient for accurate estimates of home range size. However, the commonly used 95% isopleth should be avoided; we recommend using isopleths between 90 and 50%. 5. Using the same number of fixes does not guarantee unbiased home range estimates: statistical inferences differ with the number of days sampled, even if using KDE methods. 6. The MCP method was highly inefficient and results were subject to considerable and unpredictable biases. The bivariate ellipse was not the most reliable method at low sample sizes. 7. We conclude that effort should be directed at marking more individuals monitored over long periods at the expense of the sampling rate per individual. Statistical results are reliable only if the whole sampling regime is standardized. We derive practical guidelines for field studies and data analysis.
Geography is a better determinant of human genetic differentiation than ethnicity.
Individuals differ genetically in their susceptibility to particular diseases and their response to drugs. However, personalized treatments are difficult to develop, because disease susceptibility and drug response generally have poorly characterized genetic architecture. It is thus tempting to use the ethnicity of patients to capture some of the variation in allele frequencies at the genes underlying a clinical trait. The success of such a strategy depends on whether human populations can be accurately classified into discrete genetic ethnic groups. Despite the heated discussions and controversies surrounding this issue, there has been essentially no attempt so far to quantify the relative power of ethnic groups and geography at predicting the proportion of shared alleles between human populations. Here, we present the first such quantification using a dataset of 51 populations typed at 377 autosomal microsatellite markers, and show that pair-wise geographic distances across landmasses constitute a far better predictor than ethnicity. Allele-sharing between human populations worldwide decays smoothly with increasing physical distance. We discuss the relevance of these patterns for the expected distribution of variants of medical interest. The distribution patterns of gene coding for simple traits are expected to be highly heterogeneous, as most such genes experienced strong natural selection. However, variants involved in complex traits are expected to behave essentially neutrally, and we expect them to fit closely our predictions based on microsatellites. We conclude that the use of ethnicity alone will often be inadequate as a basis for medical treatment.
Pathogen-driven selection and worldwide HLA class I diversity.
The human leukocyte antigen (HLA; known as MHC in other vertebrates) plays a central role in the recognition and presentation of antigens to the immune system and represents the most polymorphic gene cluster in the human genome [1]. Pathogen-driven balancing selection (PDBS) has been previously hypothesized to explain the remarkable polymorphism in the HLA complex, but there is, as yet, no direct support for this hypothesis [2 and 3]. A straightforward prediction coming out of the PDBS hypothesis is that populations from areas with high pathogen diversity should have increased HLA diversity in relation to their average genomic diversity. We tested this prediction by using HLA class I genetic diversity from 61 human populations. Our results show that human colonization history explains a substantial proportion of HLA genetic diversity worldwide. However, between-population variation at the HLA class I genes is also positively correlated with local pathogen richness (notably for the HLA B gene), thus providing support for the PDBS hypothesis. The proportion of variations explained by pathogen richness is higher for the HLA B gene than for the HLA A and HLA C genes. This is in good agreement with both previous immunological and genetic data suggesting that HLA B could be under a higher selective pressure from pathogens.
Geography predicts neutral genetic diversity of human populations.
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Hollywood, climate change, and the public.
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The evolution of paternal care with overlapping broods.
Most attempts to model the evolution of parental care assume that caring and mating are mutually exclusive activities (i.e., individuals acquire and guard broods "sequentially"). However, in most fish and certain insects, males can keep mating and collecting additional eggs while continuing to guard broods obtained earlier (i.e., males guard "overlapping" broods). We present a model of parental care with overlapping broods in which males can mate and guard simultaneously, even though there is a trade-off between these two activities. Within this framework, we show that male care is favored by short female processing times and high population densities, which minimize the mating cost of care. Relatively low mortality while guarding is also important for the stability of male care. Female care, on the other hand, is favored by long female processing times and low populations densities, which lead to longer intermating intervals. Biparental care is stable only when the cost to benefit ratio of care was not biased toward either sex. We derive quantitative estimates of fitness for different strategies for two species of assassin bugs with male and female uniparental care and show that the model predicts the correct form of care for both species. We believe our model might help explain the prevalence of male uniparental care in certain taxa, such as fish.
Filial cannibalism in teleost fish.
This review summarizes information on filial cannibalism (the act of eating one's own offspring) in teleost fish. Cannibalistic parents can either consume their whole brood (total filial cannibalism), or eat only some of the eggs in the nest (partial filial cannibalism). Offspring consumption has been argued to be adaptive under the assumption that offspring survival is traded against feeding, and that offspring can act as an alternative food source for the parents. The evidence supporting the basic predictions formulated under these assumptions is summarized for both total and partial filial cannibalism. These two forms of cannibalism differ significantly since the former represents an investment only in future reproductive success, whereas the latter can affect both present and future reproductive success. Despite a few inconsistencies in the data from laboratory and field studies, the energy-based explanation appears valid for both forms of cannibalism. Alternative non-energy-based explanations are considered, but they are unable to account for the wide distribution of this behaviour in teleosts. The intersexual conflict arising from attempts of the non-cannibal sex to minimize the cost of filial cannibalism is also discussed, together with the potential effect of this behaviour on the operational sex ratio at a population level.