Ancestry and kinship in a Late Antiquity-Early Middle Ages cemetery in the Eastern Italian Alps.

In South Tyrol (Eastern Italian Alps), during Late Antiquity-Early Middle Ages, archeological records indicate cultural hybridization among alpine groups and peoples of various origin. Using paleogenomics, we reconstructed the ancestry of 20 individuals (4th-7th cent. AD) from a cemetery to analyze whether they had heterogeneous or homogeneous ancestry and to study their social organization. The results revealed a primary genetic ancestry from southern Europe and additional ancestries from south-western, western, and northern Europe, suggesting that cultural hybridization was accompanied by complex genetic admixture. Kinship analyses found no genetic relatedness between the only two individuals buried with grave goods. Instead, a father-son pair was discovered in one multiple grave, together with unrelated individuals and one possible non-local female. These genetic findings indicate the presence of a high social status familia, which is supported by the cultural materials and the proximity of the grave to the most sacred area of the church.

Hearing Sensitivity of Primates: Recurrent and Episodic Positive Selection in Hair Cells and Stereocilia Protein-Coding Genes.

The large spectrum of hearing sensitivity observed in primates results from the impact of environmental and behavioral pressures to optimize sound perception and localization. Although evidence of positive selection in auditory genes has been detected in mammals including in Hominoids, selection has never been investigated in other primates. We analyzed 123 genes highly expressed in the inner ear of 27 primate species and tested to what extent positive selection may have shaped these genes in the order Primates tree. We combined both site and branch-site tests to obtain a comprehensive picture of the positively selected genes (PSGs) involved in hearing sensitivity, and drew a detailed description of the most affected branches in the tree. We chose a conservative approach, and thus focused on confounding factors potentially affecting PSG signals (alignment, GC-biased gene conversion, duplications, heterogeneous sequencing qualities). Using site tests, we showed that around 12% of these genes are PSGs, an α selection value consistent with average human genome estimates (10-15%). Using branch-site tests, we showed that the primate tree is heterogeneously affected by positive selection, with the black snub-nosed monkey, the bushbaby, and the orangutan, being the most impacted branches. A large proportion of these genes is inclined to shape hair cells and stereocilia, which are involved in the mechanotransduction process, known to influence frequency perception. Adaptive selection, and more specifically recurrent adaptive evolution, could have acted in parallel on a set of genes (ADGRV1, USH2A, PCDH15, PTPRQ, and ATP8A2) involved in stereocilia growth and the whole complex of bundle links connecting them, in species across different habitats, including high altitude and nocturnal environments.

Inference of population genetic parameters from an irregular time series of seasonal influenza virus sequences.

Basic summary statistics that quantify the population genetic structure of influenza virus are important for understanding and inferring the evolutionary and epidemiological processes. However, the sampling dates of global virus sequences in the last several decades are scattered nonuniformly throughout the calendar. Such temporal structure of samples and the small effective size of viral population hampers the use of conventional methods to calculate summary statistics. Here, we define statistics that overcome this problem by correcting for the sampling-time difference in quantifying a pairwise sequence difference. A simple linear regression method jointly estimates the mutation rate and the level of sequence polymorphism, thus providing an estimate of the effective population size. It also leads to the definition of Wright's FST for arbitrary time-series data. Furthermore, as an alternative to Tajima's D statistic or the site-frequency spectrum, a mismatch distribution corrected for sampling-time differences can be obtained and compared between actual and simulated data. Application of these methods to seasonal influenza A/H3N2 viruses sampled between 1980 and 2017 and sequences simulated under the model of recurrent positive selection with metapopulation dynamics allowed us to estimate the synonymous mutation rate and find parameter values for selection and demographic structure that fit the observation. We found that the mutation rates of HA and PB1 segments before 2007 were particularly high and that including recurrent positive selection in our model was essential for the genealogical structure of the HA segment. Methods developed here can be generally applied to population genetic inferences using serially sampled genetic data.

Predicting haplogroups using a versatile machine learning program (PredYMaLe) on a new mutationally balanced 32 Y-STR multiplex (CombYplex): Unlocking the full potential of the human STR mutation rate spectrum to estimate forensic parameters.

We developed a new mutationally well-balanced 32 Y-STR multiplex (CombYplex) together with a machine learning (ML) program PredYMaLe to assess the impact of STR mutability on haplogourp prediction, while respecting forensic community criteria (high DC/HD). We designed CombYplex around two sub-panels M1 and M2 characterized by average and high-mutation STR panels. Using these two sub-panels, we tested how our program PredYmale reacts to mutability when considering basal branches and, moving down, terminal branches. We tested first the discrimination capacity of CombYplex on 996 human samples using various forensic and statistical parameters and showed that its resolution is sufficient to separate haplogroup classes. In parallel, PredYMaLe was designed and used to test whether a ML approach can predict haplogroup classes from Y-STR profiles. Applied to our kit, SVM and Random Forest classifiers perform very well (average 97 %), better than Neural Network (average 91 %) and Bayesian methods (< 90 %). We observe heterogeneity in haplogroup assignation accuracy among classes, with most haplogroups having high prediction scores (99-100 %) and two (E1b1b and G) having lower scores (67 %). The small sample sizes of these classes explain the high tendency to misclassify the Y-profiles of these haplogroups; results were measurably improved as soon as more training data were added. We provide evidence that our ML approach is a robust method to accurately predict haplogroups when it is combined with a sufficient number of markers, well-balanced mutation rate Y-STR panels, and large ML training sets. Further research on confounding factors (such as CNV-STR or gene conversion) and ideal STR panels in regard to the branches analysed can be developed to help classifiers further optimize prediction scores.

A genome-wide scan for genes under balancing selection in Drosophila melanogaster.

BACKGROUND: In the history of population genetics balancing selection has been considered as an important evolutionary force, yet until today little is known about its abundance and its effect on patterns of genetic diversity. Several well-known examples of balancing selection have been reported from humans, mice, plants, and parasites. However, only very few systematic studies have been carried out to detect genes under balancing selection. We performed a genome scan in Drosophila melanogaster to find signatures of balancing selection in a derived (European) and an ancestral (African) population. We screened a total of 34 genomes searching for regions of high genetic diversity and an excess of SNPs with intermediate frequency. RESULTS: In total, we found 183 candidate genes: 141 in the European population and 45 in the African one, with only three genes shared between both populations. Most differences between both populations were observed on the X chromosome, though this might be partly due to false positives. Functionally, we find an overrepresentation of genes involved in neuronal development and circadian rhythm. Furthermore, some of the top genes we identified are involved in innate immunity. CONCLUSION: Our results revealed evidence of genes under balancing selection in European and African populations. More candidate genes have been found in the European population. They are involved in several different functions.

Balancing selection on immunity genes: review of the current literature and new analysis in Drosophila melanogaster.

Balancing selection has been widely assumed to be an important evolutionary force, yet even today little is known about its abundance and its impact on the patterns of genetic diversity. Several studies have shown examples of balancing selection in humans, plants or parasites, and many genes under balancing selection are involved in immunity. It has been proposed that host-parasite coevolution is one of the main forces driving immune genes to evolve under balancing selection. In this paper, we review the literature on balancing selection on immunity genes in several organisms, including Drosophila. Furthermore, we performed a genome scan for balancing selection in an African population of Drosophila melanogaster using coalescent simulations of a demographic model with and without selection. We find very few genes under balancing selection and only one novel candidate gene related to immunity. Finally, we discuss the possible causes of the low number of genes under balancing selection.

Genetic population study of Y-chromosome markers in Benin and Ivory Coast ethnic groups.

Ninety-six single nucleotide polymorphisms (SNPs) and seventeen short tandem repeat (STRs) were investigated on the Y-chromosome of 288 unrelated healthy individuals from populations in Benin (Bariba, Yoruba, and Fon) and the Ivory Coast (Ahizi and Yacouba). We performed a multidimensional scaling analysis based on FST and RST genetic distances using a large extensive database of sub-Saharan African populations. There is more genetic homogeneity in Ivory Coast populations compared with populations from Benin. Notably, the Beninese Yoruba are significantly differentiated from neighbouring groups, but also from the Yoruba from Nigeria (FST>0.05; P<0.01). The Y-chromosome dataset presented here provides new valuable data to understand the complex genetic diversity and human male demographic events in West Africa.

Determined about sex: sex-testing in 45 primate species using a 2Y/1X sex-typing assay.

Sex-testing using molecular genetic technique is routinely used in the fields of forensics, population genetics and conservation biology. However, none of the assay used so far allows a non-ambiguous and successful sex determination for human and non-human primate species. The most widely used method, AMELY/X, and its alternatives suffer from a set of drawbacks in humans and can rarely be used in New World primate species. Here, we designed a new sex-typing assay using a multiplexed PCR amplification of UTX and UTY-homologous loci and combined male-specific SRY locus. This method was successfully tested on 1048 samples, including 82 non-human primates from 45 Anthropoidea and Lemuriformes species and 966 human samples from 24 populations (Africans, Europeans, and South Americans). This sex-typing method is applicable across all primate species tested from Hominoidea to Indriidae, and also on various populations with different background origins; it represents a robust and cheap sex-typing assay to be used both by the anthropologist and primatologist communities.