A Worldwide Phylogeography for the Human X Chromosome

BACKGROUND: We reasoned that by identifying genetic markers on human X chromosome regions where recombination is rare or absent, we should be able to construct X chromosome genealogies analogous to those based on Y chromosome and mitochondrial DNA polymorphisms, with the advantage of providing information about both male and female components of the population. METHODOLOGY/PRINCIPAL FINDINGS: We identified a 47 Kb interval containing an Alu insertion polymorphism (DXS225) and four microsatellites in complete linkage disequilibrium in a low recombination rate region of the long arm of the human X chromosome. This haplotype block was studied in 667 males from the HGDP-CEPH Human Genome Diversity Panel. The haplotypic diversity was highest in Africa (0.992+/-0.0025) and lowest in the Americas (0.839+/-0.0378), where no insertion alleles of DXS225 were observed. Africa shared few haplotypes with other geographical areas, while those exhibited significant sharing among themselves. Median joining networks revealed that the African haplotypes were numerous, occupied the periphery of the graph and had low frequency, whereas those from the other continents were few, central and had high frequency. Altogether, our data support a single origin of modern man in Africa and migration to occupy the other continents by serial founder effects. Coalescent analysis permitted estimation of the time of the most recent common ancestor as 182,000 years (56,700-479,000) and the estimated time of the DXS225 Alu insertion of 94,400 years (24,300-310,000). These dates are fully compatible with the current widely accepted scenario of the origin of modern mankind in Africa within the last 195,000 years and migration out-of-Africa circa 55,000-65,000 years ago. CONCLUSIONS/SIGNIFICANCE: A haplotypic block combining an Alu insertion polymorphism and four microsatellite markers on the human X chromosome is a useful marker to evaluate genetic diversity of human populations and provides a highly informative tool for evolutionary studies

Screening fetal losses for monosomy X with a simple PCR-based procedure

To screen for monosomy X in spontaneous fetal losses we explored a simple molecular strategy based on loss of heterozygosity at highly polymorphic X-linked loci. We developed a multiplex fluorescent procedure that allows the simultaneous amplification of five dinucleotide repeat polymorphisms in a large low-recombination region in the long arm of the X chromosome. Analysis was performed by computer-assisted laser densitometry. We did not find any instances of homozygosity at all five loci in 30 normal females tested, nor among 37 women whose typing data were retrieved from the Fondation Jean Dausset - CEPH genotype database. In addition, all cases of monosomy X previously diagnosed by conventional cytogenetics presented the anticipated loss of heterozygosity at all loci. We studied 19 spontaneously aborted female fetuses and we found four samples homozygous for the five loci (21%), in good agreement with the expected rate of monosomy X in first trimester spontaneous abortions. We conclude that the loci have high diversity and high efficiency in PCR-amplification and that our multiplex procedure constitutes a simple and useful molecular screening test for monosomy X in abortions and stillbirths

Trypanosoma Cruzi : Ancestral Genomes and Population Structure

Although the genome of Trypanosoma cruzi has been completely sequenced, little is known about its population structure and evolution. Since 1999, two major evolutionary lineages presenting distinct epidemiological characteristics have been recognised: T. cruzi I and T. cruzi II. We describe new and important aspects of the population structure of the parasite, and unequivocally characterise a third ancestral lineage that we propose to name T. cruzi III. Through a careful analysis of haplotypes (blocks of genes that are stably transmitted from generation to generation of the parasite), we inferred at least two hybridisation events between the parental lineages T. cruzi II and T. cruzi III. The strain CL Brener, whose genome was sequenced, is one such hybrid. �-Based on these results, we propose a simple evolutionary model based on three ancestral genomes, T. cruzi I, T. cruzi II and T. cruzi III. At least two hybridisation events produced evolutionarily viable progeny, and T. cruzi III was the cytoplasmic donor for the resulting offspring (as identified by the mitochondrial clade of the hybrid strains) in both events. This model should be useful to inform evolutionary and pathogenetic hypotheses regarding T. cruzi