RESUMO
Sequence diversity and the ages of the deepest nodes of the MSY phylogeny remain largely unexplored due to the severely biased collection of SNPs available for study. We characterized 68 worldwide Y chromosomes by high-coverage next-generation sequencing, including 18 deep-rooting ones, and identified 2386 SNPs, 80% of which were novel. Many aspects of this pool of variants resembled the pattern observed among genome-wide de novo events, suggesting that in the MSY, a large proportion of newly arisen alleles has survived in the phylogeny. Some degree of purifying selection emerged in the form of an excess of private missense variants. Our tree recapitulated the previously known topology, but the relative lengths of major branches were drastically modified and the associated node ages were remarkably older. We found significantly different branch lengths when comparing the rare deep-rooted A1b African lineage with the rest of the tree. Our dating results and phylogeography led to the following main conclusions: (1) Patrilineal lineages with ages approaching those of early AMH fossils survive today only in central-western Africa; (2) only a few evolutionarily successful MSY lineages survived between 160 and 115 kya; and (3) an early exit out of Africa (before 70 kya), which fits recent western Asian archaeological evidence, should be considered. Our experimental design produced an unbiased resource of new MSY markers informative for the initial formation of the anatomically modern human gene pool, i.e., a period of our evolution that had been previously considered to be poorly accessible with paternally inherited markers.
Assuntos
População Negra/genética , Cromossomos Humanos Y/genética , Polimorfismo de Nucleotídeo Único/genética , Cromossomos Humanos Y/classificação , Evolução Molecular , Variação Genética , Genoma Humano , Humanos , Taxa de Mutação , Mutação de Sentido Incorreto , Filogenia , Seleção Genética , Análise de Sequência de DNARESUMO
It has long been believed that the male-specific region of the human Y chromosome (MSY) is genetically independent from the X chromosome. This idea has been recently dismissed due to the discovery that X-Y gametologous gene conversion may occur. However, the pervasiveness of this molecular process in the evolution of sex chromosomes has yet to be exhaustively analyzed. In this study, we explored how pervasive X-Y gene conversion has been during the evolution of the youngest stratum of the human sex chromosomes. By comparing about 0.5 Mb of human-chimpanzee gametologous sequences, we identified 19 regions in which extensive gene conversion has occurred. From our analysis, two major features of these emerged: 1) Several of them are evolutionarily conserved between the two species and 2) almost all of the 19 hotspots overlap with regions where X-Y crossing-over has been previously reported to be involved in sex reversal. Furthermore, in order to explore the dynamics of X-Y gametologous conversion in recent human evolution, we resequenced these 19 hotspots in 68 widely divergent Y haplogroups and used publicly available single nucleotide polymorphism data for the X chromosome. We found that at least ten hotspots are still active in humans. Hence, the results of the interspecific analysis are consistent with the hypothesis of widespread reticulate evolution within gametologous sequences in the differentiation of hominini sex chromosomes. In turn, intraspecific analysis demonstrates that X-Y gene conversion may modulate human sex-chromosome-sequence evolution to a greater extent than previously thought.
Assuntos
Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Conversão Gênica , Pan troglodytes/genética , Animais , Evolução Molecular , Feminino , Haplótipos , Humanos , Masculino , Filogenia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Cromossomo X/genética , Cromossomo Y/genéticaRESUMO
To shed light on the structure of the basal backbone of the human Y chromosome phylogeny, we sequenced about 200 kb of the male-specific region of the human Y chromosome (MSY) from each of seven Y chromosomes belonging to clades A1, A2, A3, and BT. We detected 146 biallelic variant sites through this analysis. We used these variants to construct a patrilineal tree, without taking into account any previously reported information regarding the phylogenetic relationships among the seven Y chromosomes here analyzed. There are several key changes at the basal nodes as compared with the most recent reference Y chromosome tree. A different position of the root was determined, with important implications for the origin of human Y chromosome diversity. An estimate of 142 KY was obtained for the coalescence time of the revised MSY tree, which is earlier than that obtained in previous studies and easier to reconcile with plausible scenarios of modern human origin. The number of deep branchings leading to African-specific clades has doubled, further strengthening the MSY-based evidence for a modern human origin in the African continent. An analysis of 2204 African DNA samples showed that the deepest clades of the revised MSY phylogeny are currently found in central and northwest Africa, opening new perspectives on early human presence in the continent.
Assuntos
Cromossomos Humanos Y/classificação , Cromossomos Humanos Y/genética , Filogenia , África , Alelos , Variação Genética , Humanos , Masculino , Análise de Sequência de DNARESUMO
Different X-homologous regions of the male-specific portion of the human Y chromosome (MSY) are characterized by a different content of putative single nucleotide polymorphisms (SNPs), as reported in public databases. The possible role of X-to-Y nonallelic gene conversion in contributing to these differences remains poorly understood. We explored this issue by analyzing sequence variation in three regions of the MSY characterized by a different degree of X-Y similarity and a different density of putative SNPs: the PCDH11Y gene in the X-transposed (X-Y identity 99%, high putative SNP content); the TBL1Y gene in the X-degenerate (X-Y identity 86-88%, low putative SNP content); and VCY genes-containing region in the P8 palindrome (X-Y identity 95%, low putative SNP content). Present findings do not provide any evidence for gene conversion in the PCDH11Y and TBL1Y genes; they also strongly suggest that most putative SNPs of the PCDH11Y gene (and possibly the entire X-transposed region) are most likely X-Y paralogous sequence variants, which have been entered in the databases as SNPs. On the other hand, clear evidence for the VCY genes in the P8 palindrome having acted as an acceptor of X-to-Y gene conversion was obtained. A rate of 1.8 x 10(-7) X-to-Y conversions/bp/year was estimated for these genes. These findings indicate that in the VCY region of the MSY, X-to-Y gene conversion can be highly effective to increase the level of diversity among human Y chromosomes and suggest an additional explanation for the ability of the Y chromosome to retard degradation during evolution. Present data are expected to pave the way for future investigations on the role of nonallelic gene conversion in double-strand break repair and the maintenance of Y chromosome integrity.
Assuntos
Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Análise Mutacional de DNA/métodos , Evolução Molecular , Conversão Gênica , Caderinas/genética , Cromossomos Humanos X/química , Cromossomos Humanos Y/química , Humanos , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Protocaderinas , Homologia de Sequência do Ácido Nucleico , Transducina/genéticaRESUMO
The quest to explain demographic history during the early part of human evolution has been limited because of the scarce paleoanthropological record from the Middle Stone Age. To shed light on the structure of the mitochondrial DNA (mtDNA) phylogeny at the dawn of Homo sapiens, we constructed a matrilineal tree composed of 624 complete mtDNA genomes from sub-Saharan Hg L lineages. We paid particular attention to the Khoi and San (Khoisan) people of South Africa because they are considered to be a unique relic of hunter-gatherer lifestyle and to carry paternal and maternal lineages belonging to the deepest clades known among modern humans. Both the tree phylogeny and coalescence calculations suggest that Khoisan matrilineal ancestry diverged from the rest of the human mtDNA pool 90,000-150,000 years before present (ybp) and that at least five additional, currently extant maternal lineages existed during this period in parallel. Furthermore, we estimate that a minimum of 40 other evolutionarily successful lineages flourished in sub-Saharan Africa during the period of modern human dispersal out of Africa approximately 60,000-70,000 ybp. Only much later, at the beginning of the Late Stone Age, about 40,000 ybp, did introgression of additional lineages occur into the Khoisan mtDNA pool. This process was further accelerated during the recent Bantu expansions. Our results suggest that the early settlement of humans in Africa was already matrilineally structured and involved small, separately evolving isolated populations.
Assuntos
DNA Mitocondrial/genética , Evolução Molecular , Variação Genética , Genética Populacional , Modelos Genéticos , Filogenia , Haplótipos , Humanos , Dados de Sequência MolecularRESUMO
Although geneticists have extensively debated the mode by which agriculture diffused from the Near East to Europe, they have not directly examined similar agropastoral diffusions in Africa. It is unclear, for example, whether early instances of sheep, cows, pottery, and other traits of the pastoralist package were transmitted to southern Africa by demic or cultural diffusion. Here, we report a newly discovered Y-chromosome-specific polymorphism that defines haplogroup E3b1f-M293. This polymorphism reveals the monophyletic relationship of the majority of haplotypes of a previously paraphyletic clade, E3b1-M35*, that is widespread in Africa and southern Europe. To elucidate the history of the E3b1f haplogroup, we analyzed this haplogroup in 13 populations from southern and eastern Africa. The geographic distribution of the E3b1f haplogroup, in association with the microsatellite diversity estimates for populations, is consistent with an expansion through Tanzania to southern-central Africa. The data suggest this dispersal was independent of the migration of Bantu-speaking peoples along a similar route. Instead, the phylogeography and microsatellite diversity of the E3b1f lineage correlate with the arrival of the pastoralist economy in southern Africa. Our Y-chromosomal evidence supports a demic diffusion model of pastoralism from eastern to southern Africa approximately 2,000 years ago.
Assuntos
Agricultura/história , Cromossomos Humanos Y/genética , Demografia , Emigração e Imigração/história , Genética Populacional , Cromatografia Líquida de Alta Pressão , Genótipo , Haplótipos/genética , História Antiga , Humanos , Masculino , Repetições de Microssatélites/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética , TanzâniaRESUMO
Period 2 (PER2) is a key component of the mammalian circadian clock machinery. In humans, genetic variation of clock genes or chronic disturbance of circadian rhythmicity has been implied in the onset of several phenotypes, ranging from periodic insomnias to advanced or delayed sleep phases, to more severe disorders. Peculiar geographic diversity patterns in circadian genes might represent an adaptive response to different light/dark cycles or environmental changes to which different human populations are exposed. To investigate the degree and nature of PER2 gene variation in human populations of different geographic origin, and its possible correlation with different latitudes, we sequenced a 7.7 kb portion of the gene in 20 individuals worldwide. In total, 25 variable sites were identified. The geographic distribution of haplotypes defined by five polymorphic sites was analyzed in 499 individuals from 11 populations from four continents. No evidence for latitude-driven selective effects on PER2 genetic variability was found. However, a high and significant difference in the geographic distribution of PER2 polymorphisms was observed between Africans and non-Africans, suggesting a history of geographically restricted natural selection at this locus. In support of this notion, we found several signals for selection in the sequences. The putative selected haplotype showed a recent coalescent age (8.7 Kyr), and an unusually high frequency in non-African populations. Overall, these findings indicate that a human clock-relevant gene, PER2, might have been influenced by positive selection, and offer preliminary insights into the evolution of this functional class of genes.
Assuntos
Variação Genética/fisiologia , Proteínas Nucleares/genética , Grupos Populacionais/genética , Seleção Genética , Fatores de Transcrição/genética , África , América , Ásia , Relógios Biológicos/genética , Europa (Continente) , Frequência do Gene , Genótipo , Humanos , Indígenas Norte-Americanos/genética , Oceania , Proteínas Circadianas Period , FilogeniaRESUMO
In a previous issue of AJHB, Fernandes et al. (2008. Am J Hum Biol 20:185-190.) describe instances of identity by state at multiple short tandem repeat loci between human Y chromosomes belonging to different E-M35 sub-haplogroups. They interpret these findings as evidence for multiple mutational events in at least two loci (M78 and M81). Here, we introduce a novel polymorphic marker (V68), potentially useful to investigate the issue. This marker and sequence data, reported here for the first time, reinforce our previous interpretations on the phylogenetic structure of the E3b haplogroup. We discuss these results in the frame of general approaches to attain robust phylogenetic inferences based on biallelic polymorphism data.
Assuntos
Cromossomos Humanos Y/genética , Mutação , Polimorfismo de Nucleotídeo Único , População Negra/genética , Marcadores Genéticos , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , FilogeniaRESUMO
The presence of Africans in Britain has been recorded since Roman times, but has left no apparent genetic trace among modern inhabitants. Y chromosomes belonging to the deepest-rooting clade of the Y phylogeny, haplogroup (hg) A, are regarded as African-specific, and no examples have been reported from Britain or elsewhere in Western Europe. We describe the presence of an hgA1 chromosome in an indigenous British male; comparison with African examples suggests a Western African origin. Seven out of 18 men carrying the same rare east-Yorkshire surname as the original male also carry hgA1 chromosomes, and documentary research resolves them into two genealogies with most-recent-common-ancestors living in Yorkshire in the late 18th century. Analysis using 77 Y-short tandem repeats (STRs) is consistent with coalescence a few generations earlier. Our findings represent the first genetic evidence of Africans among 'indigenous' British, and emphasize the complexity of human migration history as well as the pitfalls of assigning geographical origin from Y-chromosomal haplotypes.
Assuntos
População Negra/genética , Cromossomos Humanos Y/genética , Genética Populacional , Inglaterra , Haplótipos , Humanos , Masculino , Repetições de MicrossatélitesRESUMO
High mutation rate in mammalian mitochondrial DNA generates a highly divergent pool of alleles even within species that have dispersed and expanded in size recently. Phylogenetic analysis of 277 human mitochondrial genomes revealed a significant (P < 0.01) excess of rRNA and nonsynonymous base substitutions among hotspots of recurrent mutation. Most hotspots involved transitions from guanine to adenine that, with thymine-to-cytosine transitions, illustrate the asymmetric bias in codon usage at synonymous sites on the heavy-strand DNA. The mitochondrion-encoded tRNAThr varied significantly more than any other tRNA gene. Threonine and valine codons were involved in 259 of the 414 amino acid replacements observed. The ratio of nonsynonymous changes from and to threonine and valine differed significantly (P = 0.003) between populations with neutral (22/58) and populations with significantly negative Tajima's D values (70/76), independent of their geographic location. In contrast to a recent suggestion that the excess of nonsilent mutations is characteristic of Arctic populations, implying their role in cold adaptation, we demonstrate that the surplus of nonsynonymous mutations is a general feature of the young branches of the phylogenetic tree, affecting also those that are found only in Africa. We introduce a new calibration method of the mutation rate of synonymous transitions to estimate the coalescent times of mtDNA haplogroups.
Assuntos
DNA Mitocondrial/genética , Evolução Molecular , Genoma Humano , Mitocôndrias/genética , Seleção Genética , Substituição de Aminoácidos , Pareamento de Bases , Sequência de Bases , Códon/genética , Humanos , Dados de Sequência Molecular , Mutação/genética , Filogenia , RNA Ribossômico/genéticaRESUMO
The human Y chromosome haplogroup E-M78 (E3b1a) occurs commonly and is distributed in northern and eastern Africa, western Asia, and all of Europe. Previously, only two rarely observed internal biallelic markers (UEPs) were known within the E-M78 clade. Here we report the identification of six novel UEPs that significantly refine the phylogeny of this haplogroup. Then, we evaluate the correspondence between the newly defined sub-haplogroups and the E-M78 haplotype clusters previously identified by an 11-microsatellite loci-based network encompassing 232 chromosomes (Cruciani et al., 2004). We observed considerable correspondence between the trees generated by the two types of markers, but also noted important discrepancies between microsatellite and UEP findings. Overall, this analysis reveals that the currently visible terminal branches of the Y tree still contain a large amount of information, in terms of undiscovered biallelic markers, and that caution is needed when using the microsatellite alleles as surrogates of unique event polymorphisms.
Assuntos
Cromossomos Humanos Y/classificação , Haplótipos , Repetições de Microssatélites , África Oriental , África do Norte , Cromatografia Líquida de Alta Pressão , Análise Mutacional de DNA , Europa (Continente) , Evolução Molecular , Marcadores Genéticos , Humanos , Masculino , Oriente Médio , Filogenia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Rare mitochondrial lineages with relict distributions can sometimes be disproportionately informative about deep events in human prehistory. We have studied one such lineage, haplogroup R0a, which uniquely is most frequent in Arabia and the Horn of Africa, but is distributed much more widely, from Europe to India. We conclude that: (1) the lineage ancestral to R0a is more ancient than previously thought, with a relict distribution across the Mediterranean/Southwest Asia; (2) R0a has a much deeper presence in Arabia than previously thought, highlighting the role of at least one Pleistocene glacial refugium, perhaps on the Red Sea plains; (3) the main episode of dispersal into Eastern Africa, at least concerning maternal lineages, was at the end of the Late Glacial, due to major expansions from one or more refugia in Arabia; (4) there was likely a minor Late Glacial/early postglacial dispersal from Arabia through the Levant and into Europe, possibly alongside other lineages from a Levantine refugium; and (5) the presence of R0a in Southwest Arabia in the Holocene at the nexus of a trading network that developed after ~3 ka between Africa and the Indian Ocean led to some gene flow even further afield, into Iran, Pakistan and India.
Assuntos
DNA Mitocondrial/genética , Fluxo Gênico , Genoma Mitocondrial , Migração Humana/história , Filogenia , Refúgio de Vida Selvagem , África Oriental , Teorema de Bayes , DNA Mitocondrial/classificação , História Antiga , Migração Humana/tendências , Humanos , Camada de Gelo , Região do Mediterrâneo , Filogeografia , Análise Espaço-TemporalRESUMO
Factors affecting the rate and pattern of the mutational process are being identified for human autosomes, but the same relationships for the male specific portion of the Y chromosome (MSY) are not established. We considered 3,390 mutations occurring in 19 sequence bins identified by sequencing 1.5 Mb of the MSY from each of 104 present-day chromosomes. The occurrence of mutations was not proportional to the amount of sequenced bases in each bin, with a 2-fold variation. The regression of the number of mutations per unit sequence against a number of indicators of the genomic features of each bin, revealed the same fundamental patterns as in the autosomes. By considering the sequences of the same region from two precisely dated ancient specimens, we obtained a calibrated region-specific substitution rate of 0.716 × 10-9/site/year. Despite its lack of recombination and other peculiar features, the MSY then resembles the autosomes in displaying a marked regional heterogeneity of the mutation rate. An immediate implication is that a given figure for the substitution rate only makes sense if bound to a specific DNA region. By strictly applying this principle we obtained an unbiased estimate of the antiquity of lineages relevant to the genetic history of the human Y chromosome. In particular, the two deepest nodes of the tree highlight the survival, in Central-Western Africa, of lineages whose coalescence (291 ky, 95% C.I. 253-343) predates the emergence of anatomically modern features in the fossil record.
Assuntos
Cromossomos Humanos Y , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Mutação , FilogeniaRESUMO
Haplogroup E, defined by mutation M40, is the most common human Y chromosome clade within Africa. To increase the level of resolution of haplogroup E, we disclosed the phylogenetic relationships among 729 mutations found in 33 haplogroup DE Y-chromosomes sequenced at high coverage in previous studies. Additionally, we dissected the E-M35 subclade by genotyping 62 informative markers in 5,222 samples from 118 worldwide populations. The phylogeny of haplogroup E showed novel features compared with the previous topology, including a new basal dichotomy. Within haplogroup E-M35, we resolved all the previously known polytomies and assigned all the E-M35* chromosomes to five new different clades, all belonging to a newly identified subhaplogroup (E-V1515), which accounts for almost half of the E-M35 chromosomes from the Horn of Africa. Moreover, using a Bayesian phylogeographic analysis and a single nucleotide polymorphism-based approach we localized and dated the origin of this new lineage in the northern part of the Horn, about 12 ka. Time frames, phylogenetic structuring, and sociogeographic distribution of E-V1515 and its subclades are consistent with a multistep demic spread of pastoralism within north-eastern Africa and its subsequent diffusion to subequatorial areas. In addition, our results increase the discriminative power of the E-M35 haplogroup for use in forensic genetics through the identification of new ancestry-informative markers.
Assuntos
Cromossomos Humanos Y , Haplótipos , África , Cromossomos Humanos Y/classificação , Evolução Molecular , Técnicas de Genotipagem , Migração Humana , Humanos , Masculino , Mutação , Filogenia , Filogeografia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Despite the importance of cytochrome P450 in the metabolism of many drugs, several aspects of molecular variation at one of the main loci coding for it, CYP2D6, have never been analysed so far. Here we show that it is possible to rapidly and efficiently genotype the main European allelic variants at this locus by a SNaPshot method identifying chromosomal rearrangements and nine single-nucleotide polymorphisms. Haplotypes could be reconstructed from data on 494 chromosomes in six populations of the Mediterranean region. High levels of linkage disequilibrium were found within the chromosome region screened, suggesting that CYP2D6 may be part of a genomic recombination block, and hence that, aside from unequal crossingover that led to large chromosomal rearrangements, its haplotype diversity essentially originated through the accumulation of mutations. With the only, albeit statistically insignificant, exception of Syria, haplotype frequencies do not differ among the populations studied, despite the presence among them of three well-known genetic outliers, which could be the result of common selective pressures playing a role in shaping CYP2D6 variation over the area of Europe that we surveyed.
Assuntos
Citocromo P-450 CYP2D6/genética , Variação Genética , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Região do Mediterrâneo , Mapeamento Físico do Cromossomo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
One hundred and forty-six previously detected mutations were more precisely positioned in the human Y chromosome phylogeny by the analysis of 51 representative Y chromosome haplogroups and the use of 59 mutations from literature. Twenty-two new mutations were also described and incorporated in the revised phylogeny. This analysis made it possible to identify new haplogroups and to resolve a deep trifurcation within haplogroup B2. Our data provide a highly resolved branching in the African-specific portion of the Y tree and support the hypothesis of an origin in the north-western quadrant of the African continent for the human MSY diversity.
Assuntos
Cromossomos Humanos Y/genética , Haplótipos/genética , Mutação , Filogenia , Genoma Humano , Humanos , Repetições de Microssatélites/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Haplogroup E1b1, defined by the marker P2, is the most represented human Y chromosome haplogroup in Africa. A phylogenetic tree showing the internal structure of this haplogroup was published in 2008. A high degree of internal diversity characterizes this haplogroup, as well as the presence of a set of chromosomes undefined on the basis of a derived character. Here we make an effort to update the phylogeny of this highly diverse haplogroup by including seven mutations which have been newly discovered by direct resequencing. We also try to incorporate five previously-described markers which were not, however, reported in the 2008 tree. Additionally, during the process of mapping, we found that two previously reported SNPs required a new position on the tree. There are three key changes compared to the 2008 phylogeny. Firstly, haplogroup E-M2 (former E1b1a) and haplogroup E-M329 (former E1b1c) are now united by the mutations V38 and V100, reducing the number of E1b1 basal branches to two. The new topology of the tree has important implications concerning the origin of haplogroup E1b1. Secondly, within E1b1b1 (E-M35), two haplogroups (E-V68 and E-V257) show similar phylogenetic and geographic structure, pointing to a genetic bridge between southern European and northern African Y chromosomes. Thirdly, most of the E1b1b1* (E-M35*) paragroup chromosomes are now marked by defining mutations, thus increasing the discriminative power of the haplogroup for use in human evolution and forensics.
Assuntos
Cromossomos Humanos Y/genética , Haplótipos/genética , Filogenia , Polimorfismo Genético , África , Europa (Continente) , Genética Populacional , Geografia , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
More than 2700 unrelated individuals from Europe, northern Africa and western Asia were analyzed for the marker M269, which defines the Y chromosome haplogroup R1b1b2. A total of 593 subjects belonging to this haplogroup were identified and further analyzed for two SNPs, U106 and U152, which define haplogroups R1b1b2g and R1b1b2h, respectively. These haplogroups showed quite different frequency distribution patterns within Europe, with frequency peaks in northern Europe (R1b1b2g) and northern Italy/France (R1b1b2h).
Assuntos
Cromossomos Humanos Y , Polimorfismo de Nucleotídeo Único , Haplótipos , HumanosRESUMO
Although human Y chromosomes belonging to haplogroup R1b are quite rare in Africa, being found mainly in Asia and Europe, a group of chromosomes within the paragroup R-P25(*) are found concentrated in the central-western part of the African continent, where they can be detected at frequencies as high as 95%. Phylogenetic evidence and coalescence time estimates suggest that R-P25(*) chromosomes (or their phylogenetic ancestor) may have been carried to Africa by an Asia-to-Africa back migration in prehistoric times. Here, we describe six new mutations that define the relationships among the African R-P25(*) Y chromosomes and between these African chromosomes and earlier reported R-P25 Eurasian sub-lineages. The incorporation of these new mutations into a phylogeny of the R1b haplogroup led to the identification of a new clade (R1b1a or R-V88) encompassing all the African R-P25(*) and about half of the few European/west Asian R-P25(*) chromosomes. A worldwide phylogeographic analysis of the R1b haplogroup provided strong support to the Asia-to-Africa back-migration hypothesis. The analysis of the distribution of the R-V88 haplogroup in >1800 males from 69 African populations revealed a striking genetic contiguity between the Chadic-speaking peoples from the central Sahel and several other Afroasiatic-speaking groups from North Africa. The R-V88 coalescence time was estimated at 9.2-5.6 [corrected] kya, in the early mid Holocene. We suggest that R-V88 is a paternal genetic record of the proposed mid-Holocene migration of proto-Chadic Afroasiatic speakers through the Central Sahara into the Lake Chad Basin, and geomorphological evidence is consistent with this view.