Early human colonization, climate change and megafaunal extinction in Madagascar: The contribution of genetics in a framework of reciprocal causations

The extinction of the megafauna inMadagascar and surrounding archipelagos (Seychelles, Comoro, and Mascarene islands) has been associated with evidence of ecological transformations, explained either by the increase of human activities (Hixon et al., 2018, 2021; Douglass et al., 2019; Godfrey et al., 2019; Railsback et al., 2020) or hydroclimatic shifts (Virah-Sawmy et al., 2009; Quéméré et al., 2012) or a combination of both (Salmona et al., 2017; Li et al., 2020; Teixeira et al., 2021). Whereas the Mascarenes lost their large-bodied endemic species within two centuries, in close association with human arrival (1638–1691 CE), in Madagascar the process has been estimated to be far slower, over a period of two millennia from 2,400 to 500 cal yBP (Godfrey et al., 2019). The temporal overlap of climate- and human-induced impact makes it challenging to discern primary from secondary causes (Burney et al., 2004; Crowley, 2010). Thus, any ultimate assessment would need an understanding of the phases of human occupation coupled with a finer temporal resolution of regional climate and ecological variability. Over the last few years, the question has been addressed by contributions from a wide spectrum of disciplines, of which genetics and genomics are among the most promising (e.g., Quéméré et al., 2012; Williams et al., 2020). The results show a complex web of relationships between possible causal factors. These findings offer the opportunity to reconsider both human and climatic factors as agents that can trigger ecological outcomes through processes of direct and indirect causal chains

On the Origins and Admixture of Malagasy: New Evidence from High-Resolution Analyses of Paternal and Maternal Lineages

The Malagasy have been shown to be a genetically admixed population combining parental lineages with African and South East Asian ancestry. In the present paper, we fit the Malagasy admixture history in a highly resolved phylogeographic framework by typing a large set of mitochondrial DNA and Y DNA markers in unrelated individuals from inland (Merina) and coastal (Antandroy, Antanosy, and Antaisaka) ethnic groups. This allowed performance of a multilevel analysis in which the diversity among main ethnic divisions, lineage ancestries, and modes of inheritance could be concurrently evaluated. Admixture was confirmed to result from the encounter of African and Southeast Asian people with minor recent male contributions from Europe. However, new scenarios are depicted about Malagasy admixture history. The distribution of ancestral components was ethnic and sex biased, with the Asian ancestry appearing more conserved in the female than in the male gene pool and in inland than in coastal groups. A statistic based on haplotype sharing (D(HS)), showing low sampling error and time linearity over the last 200 generations, was introduced here for the first time and helped to integrate our results with linguistic and archeological data. The focus about the origin of Malagasy lineages was enlarged in space and pushed back in time. Homelands could not be pinpointed but appeared to comprise two vast areas containing different populations from sub-Saharan Africa and South East Asia. The pattern of diffusion of uniparental lineages was compatible with at least two events: a primary admixture of proto-Malay people with Bantu speakers bearing a western-like pool of haplotypes, followed by a secondary flow of Southeastern Bantu speakers unpaired for gender (mainly male driven) and geography (mainly coastal)

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7–8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry

Stuck in fragments: Population genetics of the Endangered collared brown lemur Eulemur collaris in the Malagasy littoral forest

Objectives The Endangered collared brown lemur (Eulemur collaris) is the largest primate living in the littoral forest of southeastern Madagascar, a top priority habitat for biodiversity conservation on the island. Because this lemur is a key seed-disperser, an evaluation of the structure and connectivity of the populations surviving in the forest fragments is urgently needed to guide conservation plans. Materials and Methods Genetic variability at autosomal microsatellites and mitochondrial DNA was investigated in a total of 49 collared brown lemurs sampled by non-invasive methods in three littoral forest fragments and in the nearby lowland humid forest. Results The overall genetic diversity of E. collaris in the southeastern coastal region of Madagascar was lower than in other populations, as well as in other lemur species. The population appears highly structured, with less variable and more inbred groups inhabiting the littoral forest fragments compared to the inland area. Major barriers to gene flow were identified isolating littoral forest fragments from each other and from the inland lowland humid forest. Discussion Medium to long-term drift and scarce gene flow is the scenario that best explains the current genetic distribution. Habitat discontinuities such as rivers and grassland between forest fragments played a major role in structuring the population. A common history of size contraction is pointed out by several genetic estimators, indicating a possible ecological crisis triggered around 1,300 years ago. The adoption of strategies aimed at facilitating gene flow and population growth appears crucial to delay further loss of genetic diversity

Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women

Abstract Background Iron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs) known to be related to iron metabolism were studied in menstruating women. Methods A group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA) test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141) was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression. Results Four variants, two in the transferrin gene (rs3811647, rs1799852) and two in the HFE gene (C282Y, H63D), explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found. Conclusions In contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk.This study was supported by Project AGL2009-11437. R.Blanco-Rojo was supported by a JAE-predoc grant from CSIC and European Social Found, S.Bertoncini by Grupo Santander 2009 (Estancia doctores y tecnologos UCM), and J.M.Soria by "Programa d'Estabilització d'Investigadors de la Direcció d'Estrategia i Coordinació del Departament de Salut".Peer Reviewe

Increased efficiency in geographic ancestry assignment and human identification by combining lineage profiles: The case of the iranians

OBJECTIVES: This research is a first empirical attempt to quantify the increase of the among-groups variance and the probative value of a DNA evidence when combining profiles based on markers with uniparental inheritance. METHODS: Yfiler and HVS-I panels of loci were analyzed in 130 healthy unrelated males from six Iranian native groups. RESULTS: A separate analysis of DNA profiles at the two lineage markers failed to detect a population substructure, whereas maximum levels of genetic diversity (HD\u2009=\u20091) and discrimination capacity (DC\u2009=\u20091) were obtained by combining the two profiles. CONCLUSIONS: When combined, the forensic efficiency of routinely used panels of lineage markers can be largely sufficient to resolve cases of geographic ancestry and human identification even in genetically homogeneous populations

Dynamic Effects of Topoisomerase I Inhibition on R-Loops and Short Transcripts at Active Promoters.

Topoisomerase I-DNA-cleavage complexes (Top1cc) stabilized by camptothecin (CPT) have specific effects at transcriptional levels. We recently reported that Top1cc increase antisense transcript (aRNAs) levels at divergent CpG-island promoters and, transiently, DNA/RNA hybrids (R-loop) in nuclear and mitochondrial genomes of colon cancer HCT116 cells. However, the relationship between R-loops and aRNAs was not established. Here, we show that aRNAs can form R-loops in N-TERA-2 cells under physiological conditions, and that promoter-associated R-loops are somewhat increased and extended in length immediately upon cell exposure to CPT. In contrast, persistent Top1ccs reduce the majority of R-loops suggesting that CPT-accumulated aRNAs are not commonly involved in R-loops. The enhancement of aRNAs by Top1ccs is present both in human colon cancer HCT116 cells and WI38 fibroblasts suggesting a common response of cancer and normal cells. Although Top1ccs lead to DSB and DDR kinases activation, we do not detect a dependence of aRNA accumulation on ATM or DNA-PK activation. However, we showed that the cell response to persistent Top1ccs can involve an impairment of aRNA turnover rather than a higher synthesis rate. Finally, a genome-wide analysis shows that persistent Top1ccs also determine an accumulation of sense transcripts at 5'-end gene regions suggesting an increased occurrence of truncated transcripts. Taken together, the results indicate that Top1 may regulate transcription initiation by modulating RNA polymerase-generated negative supercoils, which can in turn favor R-loop formation at promoters, and that transcript accumulation at TSS is a response to persistent transcriptional stress by Top1 poisoning

CPT modulates sense transcription in a particular subset of genes.

<p>Sense tags distribution along non-overlapping Refseq genes of HCT116 cells and HCT116-shRNATop1 cells, were analyzed in a region from 2000 bases upstream the TSS to 2000 bases downstream the TES using NGSplot software. Here, genes have been divided in two groups based on their FPKM. These genes have been selected for an accumulation of sense reads in the 5’ region (CPT-reads minus Control-reads: 10 ≥ 100) and a reduction of sense reads at the 3’ region (CPT-reads minus Control-reads: ≤ 5). Furthermore, genes selected have a fold change above 2 and a minimum number of sense reads above 5 in the 5’ region of CPT treated sample. Reads were normalized to the length of each region (1000 bp). Control reads are reported in gray dotted line and CPT reads in black line. Black arrows indicate an accumulation or not of reads at 5’ level after CPT treatment (10 μM for 4 hours).</p