The Genetic Origin of Daunians and the Pan-Mediterranean Southern Italian Iron Age Context.

The geographical location and shape of Apulia, a narrow land stretching out in the sea at the South of Italy, made this region a Mediterranean crossroads connecting Western Europe and the Balkans. Such movements culminated at the beginning of the Iron Age with the Iapygian civilization which consisted of three cultures: Peucetians, Messapians, and Daunians. Among them, the Daunians left a peculiar cultural heritage, with one-of-a-kind stelae and pottery, but, despite the extensive archaeological literature, their origin has been lost to time. In order to shed light on this and to provide a genetic picture of Iron Age Southern Italy, we collected and sequenced human remains from three archaeological sites geographically located in Northern Apulia (the area historically inhabited by Daunians) and radiocarbon dated between 1157 and 275 calBCE. We find that Iron Age Apulian samples are still distant from the genetic variability of modern-day Apulians, they show a degree of genetic heterogeneity comparable with the cosmopolitan Republican and Imperial Roman civilization, even though a few kilometers and centuries separate them, and they are well inserted into the Iron Age Pan-Mediterranean genetic landscape. Our study provides for the first time a window on the genetic make-up of pre-Roman Apulia, whose increasing connectivity within the Mediterranean landscape, would have contributed to laying the foundation for modern genetic variability. In this light, the genetic profile of Daunians may be compatible with an at least partial autochthonous origin, with plausible contributions from the Balkan peninsula

Approaching heterogeneity of human epidermal growth factor receptor 2 in surgical specimens of gastric cancer.

Summary Gastric cancer shows intratumoral heterogeneity for human epidermal growth factor receptor 2 expression. We evaluated whether the number of tissue blocks analyzed or the antibodies used may influence the immunohistochemical results in gastrectomy specimens. Clinicopathologic data from 148 patients receiving gastric surgery for cancer were collected. One tissue block for each of 88 primary tumors and 60 paired primary tumors and metastases was examined for human epidermal growth factor receptor 2 status by immunohistochemistry using 3 different antibodies (HercepTest, CB11, and 4B5) and by fluorescent in situ hybridization. Two additional tissue blocks of the primary tumor were tested by immunohistochemistry if the results were negative on the first tissue block. The concordance among the 3 antibodies was 94.5% (testing 1 tissue block). Two cases showed a clinically significant discrepancy between primary tumor (score 0) and lymph nodes metastases (score 3+). Additional block analysis increased both the sensitivity (from 63% to 83%) and the accuracy (from 91% to 94%) of immunohistochemistry as compared with fluorescent in situ hybridization. The multiblock approach could potentially identify a greater number of human epidermal growth factor receptor 2–positive gastric cancers, particularly those with higher levels of intratumor heterogeneity. In turn, human epidermal growth factor receptor 2 positivity correlated with a worse prognosis ( P = .011) and was an independent variable in multivariate analysis (hazard ratio, 1.57). In conclusion, testing more than 1 tissue block of cancer from specimens of gastric resection provides a more reliable human epidermal growth factor receptor 2 assessment regardless of the antibody used

Assessing temporal and geographic contacts across the Adriatic Sea through the analysis of genome-wide data from Southern Italy

AbstractSouthern Italy was characterised by a complex prehistory that started with different Palaeolithic cultures, later followed by the Neolithic transition and the demic dispersal from the Pontic-Caspian Steppe during the Bronze Age. Archaeological and historical evidence points to demic and cultural influences between Southern Italians and the Balkans, starting with the initial Palaeolithic occupation until historical and modern times. To shed light on the dynamics of these contacts, we analysed a genome-wide SNP dataset of more than 700 individuals from the South Mediterranean area (102 from Southern Italy), combined with ancient DNA from neighbouring areas. Our findings revealed high affinities of South-Eastern Italians with modern Eastern Peloponnesians, and a closer affinity of ancient Greek genomes with those from specific regions of South Italy than modern Greek genomes. The higher similarity could be associated with the presence of a Bronze Age component ultimately originating from the Caucasus and characterised by high frequencies of Iranian and Anatolian Neolithic ancestries. Furthermore, to reveal possible signals of natural selection, we looked for extremely differentiated allele frequencies among Northern and Southern Italy, uncovering putatively adapted SNPs in genes involved in alcohol metabolism, nevi features and immunological traits, such as ALDH2, NID1 and CBLB

Continental-scale genomic analysis suggests shared post-admixture adaptation in the Americas

We thank the people working at the High Performance Computing Center of the University of Tartu for the help and support provided. We thank Marco Rosario Capodiferro for useful discussions. This work was supported by the European Union through the European Regional Development Fund (Project No. 20142020.4.01.16-0030 to LO, MMe, FM; Project No. 2014-2020.4.01.160271 to RF; Project No. 2014-2020.4.01.16-0125 to RF; Project No. 2014-2020.4.01.16-0024 to DM, LP). This work was supported by the Estonian Research Council grant PUT (PRG243) (to RF, MMe, LP). This work was supported by institutional research funding IUT (IUT24-1) of the EstonianMinistry of Education and Research (to TK). This research was supported by the European Union through Horizon 2020 grant no. 810645 (to MMe). This research was supported by the European Union through the Horizon 2020 research and innovation programme under grant no 810645 and through the European Regional Development Fund project no. MOBEC008 to MMo.American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, even though gene f low could drive adaptive evolution, it is unclear whether and how natural selection acted on the resulting genetic variation in the Americas. In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for ∼6000 admixed individuals from 10 American countries. In doing so, we identified regions characterized by a divergent ancestry profile (DAP), in which a significant over or under ancestral representation is evident. Our results highlighted a series of genomic regions with DAPs associated with immune system response and relevant medical traits, with the longest DAP region encompassing the human leukocyte antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analysing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts and characterized by a high deleteriousness score. Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at a continental scale in the Americas, affecting more often functional and impactful genomic variants.European Commission 2014-2020.4.01.16-0030 2014-2020.4.01.16-0271 2014-2020.4.01.16-0125 2014-2020.4.01.16-0024 MOBEC008Estonian Research Council grant PUT PRG243institutional research funding IUT of the Estonian Ministry of Education and Research IUT24-1European Union through Horizon 2020 grant 81064

Genomic variation in baboons from central Mozambique unveils complex evolutionary relationships with other Papio species

Background Gorongosa National Park in Mozambique hosts a large population of baboons, numbering over 200 troops. Gorongosa baboons have been tentatively identified as part of Papio ursinus on the basis of previous limited morphological analysis and a handful of mitochondrial DNA sequences. However, a recent morphological and morphometric analysis of Gorongosa baboons pinpointed the occurrence of several traits intermediate between P. ursinus and P. cynocephalus, leaving open the possibility of past and/or ongoing gene flow in the baboon population of Gorongosa National Park. In order to investigate the evolutionary history of baboons in Gorongosa, we generated high and low coverage whole genome sequence data of Gorongosa baboons and compared it to available Papio genomes. Results We confirmed that P. ursinus is the species closest to Gorongosa baboons. However, the Gorongosa baboon genomes share more derived alleles with P. cynocephalus than P. ursinus does, but no recent gene flow between P. ursinus and P. cynocephalus was detected when available Papio genomes were analyzed. Our results, based on the analysis of autosomal, mitochondrial and Y chromosome data, suggest complex, possibly male-biased, gene flow between Gorongosa baboons and P. cynocephalus, hinting to direct or indirect contributions from baboons belonging to the “northern” Papio clade, and signal the presence of population structure within P. ursinus. Conclusions The analysis of genome data generated from baboon samples collected in central Mozambique highlighted a complex set of evolutionary relationships with other baboons. Our results provided new insights in the population dynamics that have shaped baboon diversity.info:eu-repo/semantics/publishedVersio

Eesti, Euroopa ja üleilmsete inimgenoomide geneetilise päritolu kihtide lahtikaevamine

Väitekirja elektrooniline versioon ei sisalda publikatsiooneTänapäeval eeldame sageli, et meie moodne eluviis on minevikust parem, ja et mida kaugemale me ajas tagasi läheme, seda enam heitlesid mineviku inimesed kehvade elutingimuste või küündimatu tehnoloogiaga. Pole üllatav, et ajaloolised ja arheoloogilised uuringud äratavad meist paljude uudishimu – nende tõttu oleme sunnitud oma tänapäevast uskumuste süsteemi ümber kujundama ning jahmuma sellest, kui palju mineviku populatsioonid tegelikult saavutada suutsid. Mineviku inimesed olid organiseerunud ühiskonnaks, nad liikusid, rändasid, jagasid ideid, kultuure ja tehnoloogiaid – ja me leiame ikka veel nende kokkupuudete jälgi. Käesoleva doktoritöö eesmärgiks mineviku kokkupuudete jälgede uurimine geneetilistes andmetes. Populatsioonide kokkupuudet nimetatakse segunemissündmuseks, mis tekitab segunenud populatsioone. Lähenemisviisiga, mida nimetatakse põlvnemise lahtiharutamiseks (Ancestry Deconvolution, AD), saame segunenud grupi geneetilist mosaiiki analüüsida, ajades segunemise osaliste jälgi, ja segunemissündmust täpsemalt iseloomustada. AD lähenemisviiside seas on meetodid, mida nimetatakse lokaalse põlvnemise tuletamiseks (Local Ancestry Inferences, LAI), mis võimaldavad tuletada antud päriliku lookuse põlvnemist. Sellistel kõrge lahutusastmega tuletustel on piirangud, mis mõnel juhul LAI tööriistade jõudlust tugevalt piiravad. Seega, rakendades LA-d segunenud populatsioonil, mida iseloomustab põlvnemine eri maailmajagudest, saame keskenduda tundmatute mineviku demograafiliste sündmuste avastamisele, kuid LA kasutamine maailmajao sisestel segunemistel, näiteks Euroopa populatsioonidel, nõuab metodoloogilist lähenemist, mis on kujundatud nii, et see võtab kõigepealt arvesse LA piiranguid. Lõpuks saame kasutada AD ja LAI lähenemisviise, et esitada küsimusi väljaspool demograafilisi uuringuid. Teatud fenotüübi väljakujunemise tõenäosust on võimalik osaliselt ennustada polügeensete skooride (Polygenic Scores, PS) abil. Kuid genoomile mõjuv tohutu hulk muutujaid on populatsioonispetsiifilised ja tuletused pole eriti ühelt populatsioonilt teisele üle kantavad, mis takistab PS-i rakendatavust vähem uuritud või segunenud populatsioonidele. Ma esitlen kolme uuringut, mis arutlevad AD ja LAI võimaluste ja piirangute üle. Uurisin segunemissündmust, milles said kokku väga erinevad populatsioonid eri maailmajagudest; väikesel skaalal segunemissündmuste, näiteks Euroopa rühmade puhul, lahtiharutamise piiranguid; ja lõpuks rakendasin kogutud teadmisi, ületamaks polügeensete skooride kasutamise piiranguid segunenud populatsioonidel.Nowadays, we often assume that our modern way of life is better than the past ones, and the more we go back in time, the more the past humans struggled with poor living conditions or unperforming technologies. It is no surprise that historical and archaeological studies tackle the curiosity of many of us: with them we are forced to reshape our modern belief system and gasp before how much past populations could in fact achieve. People in the past were organised, they moved, travelled, shared ideas, cultures and technologies: and we can still find traces of their encounters. This thesis aims to look at the residual traces of past encounters through the genetic data. The encounter of populations is referred to as admixture event and creates admixed populations. With an approach called ancestry deconvolution (AD) we can analyse the genetic mosaic of an admixed group, tracing the admixing contributors and further characterise the admixing event. Within the AD approaches, there are the methods referred to as Local Ancestry Inferences (LAI) that allows to infer which ancestry falls within a given inherited locus. Such a fine level of inferences come with constraints, highly limiting the LAI tools performances in some cases. In turn, while performing LA on an admixed population characterised by worldwide ancestries we can focus on discovering unknown past demographic events, applying LA on sub-continental admixtures, such as European populations, requires a methodological approach that must be designed to comprehend the LA limitations first. Eventually, we can leverage AD and LAI to ask questions beyond the realm of demography studies. It is possible to partially predict the probability of developing a certain phenotype with the Polygenic Scores (PS). However, the vast number of variables acting upon the genome are population-specific, and the inferences are hardly transferable from one population to another, hindering the application of PS to understudied or admixed populations. I present three studies that discuss the potentialities and limits of AD and LAI. I studied an admixture event where worldwide, highly divergent populations came together; the limitations in deconvoluting fine-scale admixture events, such as in European groups; and finally I applied the built knowledge to overcome the limitations in applying Polygenic Score on admixed populations.https://www.ester.ee/record=b550185

Anthropogenic hybridization and its influence on the adaptive potential of the Sardinian wild boar (Sus scrofa meridionalis)

: The wild boar (Sus scrofa meridionalis) arrived in Sardinia with the first human settlers in the early Neolithic with the potential to hybridize with the domestic pig (S. s. domesticus) throughout its evolution on the island. In this paper, we investigated the possible microevolutionary effects of such introgressive hybridization on the present wild boar population, comparing Sardinian wild specimens with several commercial pig breeds and Sardinian local pigs, along with a putatively unadmixed wild boar population from Central Italy, all genotyped with a medium density SNP chip. We first aimed at identifying hybrids in the population using different approaches, then examined genomic regions enriched for domestic alleles in the hybrid group, and finally we applied two methods to find regions under positive selection to possibly highlight instances of domestic adaptive introgression into a wild population. We found three hybrids within the Sardinian sample (3.1% out of the whole dataset). We reported 11 significant windows under positive selection with a method that looks for overly differentiated loci in the target population, compared with other two populations. We also identified 82 genomic regions with signs of selection in the domestic pig but not in the wild boar, two of which overlapped with genomic regions enriched for domestic alleles in the hybrid pool. Genes in these regions can be linked with reproductive success. Given our results, domestic introgression does not seem to be pervasive in the Sardinian wild boar. Nevertheless, we suggest monitoring the possible spread of advantageous domestic alleles in the coming years