Biology subjects

Mezzavilla, M.

Publications and source records attributed to Mezzavilla, M..

3 recordsLinked to original sources

bioRxiv2018

Establishment and equilibrium levels of deleterious mutations in large populations

Analytical and statistical stochastic approaches are used to model and predict the dispersion of mutations through a large population. These approaches are used to quantify the magnitude of a heterozygous selective advantage of a mutation in the presence of a homozygous disadvantage. Random effects such as genetic drift are accounted for, which are likely to extinguish even highly advantageous mutations while the prevalence is still low. Dunbars results regarding the cognitive upper limit of the number of stable social relationships that humans can maintain are used to determine a realistic community size - a reduced local subset of the total population - from which an individual can select mates. This reduction in effective population size has a dramatic effect on the probability of establishing mutations, as well as the eventual equilibrium values that are reached in the case of mutations conferring a heterozygous selective advantage, but a homozygous disadvantage, as in the case of cystic fibrosis and sickle cell disease. The magnitude of this selective advantage can then be estimated based on observed occurrence levels of a specific mutation in a population, without requiring prior information regarding its phenotypic manifestation.\n\nAuthor summaryDeleterious mutations such as cystic fibrosis and sickle cell anemia can disperse through human populations due to the selective advantage that it bestows on heterozygous carriers, depending on environmental conditions. As its prevalence increases, the probability of generating homozygous offspring, with its concomitant selective disadvantage, also grows until an eventual equilibrium is reached between the number of carriers and wild-type individuals. In this work computer modelling is used to combine Dunbars anthropological observations predicting upper bounds to the number of stable human social relationships with observed prevalence levels, to estimate the absolute magnitude of the heterozygous selective advantage bestowed by such a deleterious genetic variation, without requiring knowledge regarding the specific mechanism whereby such an advantage is manifested.

genetics↗

bioRxiv2017

Continuity and admixture in the last five millennia of Levantine history from ancient Canaanite and present-day Lebanese genome sequences

The Canaanites inhabited the Levant region during the Bronze Age and established a culture which became influential in the Near East and beyond. However, the Canaanites, unlike most other ancient Near Easterners of this period, left few surviving textual records and thus their origin and relationship to ancient and present-day populations remain unclear. In this study, we sequenced five whole-genomes from ~3,700-year-old individuals from the city of Sidon, a major Canaanite city-state on the Eastern Mediterranean coast. We also sequenced the genomes of 99 individuals from present-day Lebanon to catalogue modern Levantine genetic diversity. We find that a Bronze Age Canaanite-related ancestry was widespread in the region, shared among urban populations inhabiting the coast (Sidon) and inland populations (Jordan) who likely lived in farming societies or were pastoral nomads. This Canaanite-related ancestry derived from mixture between local Neolithic populations and eastern migrants genetically related to Chalcolithic Iranians. We estimate, using linkage-disequilibrium decay patterns, that admixture occurred 6,600-3,550 years ago, coinciding with massive population movements in the mid-Holocene triggered by aridification ~4,200 years ago. We show that present-day Lebanese derive most of their ancestry from a Canaanite-related population, which therefore implies substantial genetic continuity in the Levant since at least the Bronze Age. In addition, we find Eurasian ancestry in the Lebanese not present in Bronze Age or earlier Levantines. We estimate this Eurasian ancestry arrived in the Levant around 3,750-2,170 years ago during a period of successive conquests by distant populations such as the Persians and Macedonians.

genetics↗

bioRxiv2017

Like Sugar in Milk: Reconstructing the genetic history of the Parsi population

BackgroundThe Parsis, one of the smallest religious community in the world, reside in South Asia. Previous genetic studies on them, although based on low resolution markers, reported both Iranian and Indian ancestries. To understand the population structure and demographic history of this group in more detail, we analyzed Indian and Pakistani Parsi populations using high-resolution autosomal and uniparental (Y-chromosomal and mitochondrial DNA) markers. Additionally, we also assayed 108 mitochondrial DNA markers among 21 ancient Parsi DNA samples excavated from Sanjan, in present day Gujarat, the place of their original settlement in India.\n\nResultsOur extensive analyses indicated that among present-day populations, the Parsis are genetically closest to Middle Eastern (Iranian and the Caucasus) populations rather than their South Asian neighbors. They also share the highest number of haplotypes with present-day Iranians and we estimate that the admixture of the Parsis with Indian populations occurred [~]1,200 years ago. Enriched homozygosity in the Parsi reflects their recent isolation and inbreeding. We also observed 48% South-Asian-specific mitochondrial lineages among the ancient samples, which might have resulted from the assimilation of local females during the initial settlement.\n\nConclusionsWe show that the Parsis are genetically closest to the Neolithic Iranians, followed by present-day Middle Eastern populations rather than those in South Asia and provide evidence of sex-specific admixture from South Asians to the Parsis. Our results are consistent with the historically-recorded migration of the Parsi populations to South Asia in the 7thcentury and in agreement with their assimilation into the Indian sub-continents population and cultural milieu \"like sugar in milk\". Moreover, in a wider context our results suggest a major demographic transition in West Asia due to Islamic-conquest.

evolutionary biology↗