Giuseppe Passarino

Y chromosome sequence variation and the history of human populations

Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.

The phylogeography of Y chromosome binary haplotypes and the origins of modern human populations

Although molecular genetic evidence continues to accumulate that is consistent with a recent common African ancestry of modern humans, its ability to illuminate regional histories remains incomplete. A set of unique event polymorphisms associated with the non‐recombining portion of the Y‐chromosome (NRY) addresses this issue by providing evidence concerning successful migrations originating from Africa, which can be interpreted as subsequent colonizations, differentiations and migrations overlaid upon previous population ranges. A total of 205 markers identified by denaturing high performance liquid chromatography (DHPLC), together with 13 taken from the literature, were used to construct a parsimonious genealogy. Ancestral allelic states were deduced from orthologous great ape sequences. A total of 131 unique haplotypes were defined which trace the microevolutionary trajectory of global modern human genetic diversification. The genealogy provides a detailed phylogeographic portrait of contemporary global population structure that is emblematic of human origins, divergence and population history that is consistent with climatic, paleoanthropological and other genetic knowledge.

Y-chromosome and mtDNA polymorphisms in Iraq, a crossroad of the early human dispersal and of post-Neolithic migrations

Analyses of mtDNA and Y-chromosome variation were performed in a sample of Iraqis, a scarcely investigated population of the Fertile Crescent. A total of 216 mtDNAs were screened for the diagnostic RFLP markers of the main Eurasian and African haplogroups. A subset of these samples, whose HVS-I sequences were previously obtained, was also examined by high-resolution restriction analysis. The Y-chromosome variation was investigated in 139 subjects by using 17 biallelic markers and the 49a,f/Taq I system. For both uniparental systems, the large majority of the haplogroups observed in the Iraqi population are those (H, J, T, and U for the mtDNA, and J(xM172) and J-M172 for the Y chromosome) considered to have originated in the Middle East and to have later spread all over Western Eurasia. However, about 9% of the mtDNAs and 30% of the Y-chromosomes most likely represent arrivals from distant geographic regions. The different proportion of long-range genetic input observed for the mtDNA and the Y chromosome appears to indicate that events of gene flow to this area might have involved mainly males rather than females.

Different genetic components in the Norwegian population revealed by the analysis of mtDNA and Y chromosome polymorphisms

The genetic composition of the Norwegian population was investigated by analysing polymorphisms associated with both the mitochondrial DNA (mtDNA) and Y chromosome loci in a sample of 74 Norwegian males. The combination of their uniparental mode of inheritance and the absence of recombination make these haplotypic stretches of DNA the tools of choice in evaluating the different components of a populations gene pool. The sequencing of the Dloop and two diagnostic RFLPs (AluI 7025 and HinfI at 12u200a308) allowed us to classify the mtDNA molecules in 10 previously described groups. As for the Y chromosome the combination of binary markers and microsatellites allowed us to compare our results to those obtained elsewhere in Europe. Both mtDNA and Y chromosome polymorphisms showed a noticeable genetic affinity between Norwegians and central Europeans, especially Germans. When the phylogeographic analysis of the Y chromosome haplotypes was attempted some interesting clues on the peopling of Norway emerged. Although Y chromosome binary and microsatellite data indicate that 80% of the haplotypes are closely related to Central and western Europeans, the remainder share a unique binary marker (M17) common in eastern Europeans with informative microsatellite haplotypes suggesting a different demographic history. Other minor genetic influences on the Norwegian population from Uralic speakers and Mediterranean populations were also highlighted.

Male/female ratio in centenarians: a possible role played by population genetic structure.

All the demographic surveys on the centenarians have highlighted that females outnumber males. The centenarians male/female (M/F) ratio reported by most studies ranges between 1:4 and 1:7. A puzzling 1:2 ratio was observed in Calabria, a Southern Italian region. To our knowledge only in Sardinia a similar phenomenon had been previously observed. We have therefore used the data of the Italian Institute of Statistics to figure out the centenarians M/F ratio in the Italian regions. We found that this ratio gradually decreases from South to North. Such a result is certainly due to many factors. Thus, we have explored the possibility, it is also influenced by the genetic structure of the Italian population. In fact, the distribution of the centenarians M/F ratio turned out to be significantly correlated with the genetic structure of the Italian population as outlined by the principal component analysis.

G1m phenotypes in a sample population from Tirana (Albania)

This report presents the distribution of G1m phenotypes (allotypes z, a, x, f,) observed in a sample population from Tirana (Albania). The comparison between these data and those previously found in a sample group of Arbreshes (Albanians who live in South Italy where they immigrated about 4 centuries ago) showed that, at least for the tested markers, the cultural identity of Arbreshes is not reflected by a genetic isolation from Southern Italians.

Physical decline and survival in the elderly are affected by the genetic variability of amino acid transporter genes

Amino acid (AA) availability is a rate-limiting factor in the regulation of muscle protein metabolism and, consequently, a risk factor for age-related decline in muscle performance. AA transporters are emerging as sensors of AA availability and activators of mTORC1 signalling, acting as transceptors. Here, we evaluated the association of 58 single nucleotide polymorphisms (SNPs) in 10 selected AA transporter genes with parameters of physical performance (Hand Grip, Activity of Daily Living, Walking time). By analysing a sample of 475 subjects aged 50-89 years, we found significant associations with SLC7A5/LAT1, SLC7A8/LAT2, SLC36A1/PAT1, SLC38A2/SNAT2, SLC3A2/CD98, SLC38A7/SNAT7 genes. Further investigation of the SNPs in a cross-sectional study including 290 subjects aged 90-107 years revealed associations of SLC3A2/CD98, SLC38A2/SNAT2, SLC38A3/SNAT3, SLC38A9/SNAT9 variability with longevity. Finally, a longitudinal study examining the survival rate over 10 years showed age-dependent complexity due to possible antagonistic pleiotropic effects for a SNP in SLC38A9/SNAT9, conferring a survival advantage before 90 years of age and a disadvantage later, probably due to the remodelling of AA metabolism. On the whole, our findings support the hypothesis that AA transporters may impact on the age-related physical decline and survival at old age in a complex way, likely through a mechanism involving mTORC1 signalling.

Mitochondrial DNA polymorphisms in a sample of Albanian population (Tirana)

RFLPs of mtDNA for HpaI, BamHI, HaeII, MspI, AvaII and HincII were analysed in a sample of 100 from collected in Tirana (Albania). Eighteen mtDNA types were identified, four of which are new: two because of new morphs for Hpa/HincII (HpaI-9Tir/HincII-17Tir) and AvaII (AvaII-35Tir), and two because of new associations between morphs which were already known. Albanian data were compared with corresponding ones from Calabrians (Southern Italians) and Arbreshes (people of Albanian ancestry living in Calabria). Even though the examined mtDNA markers do not reveal important differences among the three groups, the analysis of both morphs and types shows a trend which places Arbreshes closer to Calabrians than to Albanians.

rRNA-gene methylation and biological aging

Epigenetic modifications, which are programmed across the individual’s lifespan by the genetic background but also modulated by environmental and lifestyle factors, are widely studied to identify biomarkers of human aging. Indeed, Garagnani et al. identified three genes whose methylation level strongly correlates with age [1]. Subsequently, Horvarth defined a high precise DNA methylation clock, able to predict age, with a low margin of error, based on methylation levels of a series of CpG sites scattered throughout the genome. These markers, and others which have consequently been identified, have proved to be reliable enough to be used for forensic purposes in order to define the age of human subjects by analysing these markers in different specimens (such as teeth, blood, semen) [2]. On the other hand, most of the scientists involved with research on aging are willing to identify epigenetic modifications correlated with biological rather than with chronological age. Such markers may be important firstly because the definition of biological age in the elderly may be much more useful than chronological age to identify the subjects needing (medical or social) care; secondly, because the identification of genes the methylation of which is correlated with biological aging may give important clues on the aging process and, possibly, on how to modulate it. Many hints suggest that these markers are likely to exist. For instance, global methylation showed to be correlated with biological and not with chronological age [3]. Ribosomal RNA (rRNA) genes consist of highly evolutionary conserved tandem and clusters of units within nucleolar organizer regions, distributed, in humans, on the short arms of acrocentric chromosomes. The expression of rRNA genes is regulated during different stages of lifetime by several factors, including nutrients, transcription factors and epigenetic marks as well [4, 5]. Previous studies have indicated that alterations of rRNA expression may be related to specific pathological conditions, such as different types of cancers and Alzheimer Disease [6]. In addition, the analysis of fibroblasts from patients with Werner Syndrome, and of hematopoietic cells from rats of different ages suggested a correlation with physiological and pathological aging. These data, coupled with the acknowledged importance of protein use and storage in the elderly, attracted our interest, suggesting that the expression of rRNA genes may be correlated to the functional status of old subjects Editorial