Biology subjects

Mark Stoneking

Publications and source records attributed to Mark Stoneking.

10 recordsLinked to original sources

bioRxiv2016

Complete mitochondrial genomes of Thai and Lao populations indicate an ancient origin of Austroasiatic groups and demic diffusion in the spread of Tai-Kadai languages

The Tai-Kadai (TK) language family is thought to have originated in southern China and spread to Thailand and Laos, but it is not clear if TK languages spread by demic diffusion (i.e., a migration of people from southern China) or by cultural diffusion, with native Austroasiatic (AA) speakers switching to TK languages. To address this and other questions, we obtained 1,234 complete mtDNA genome sequences from 51 TK and AA groups from Thailand and Laos. We find high genetic heterogeneity, with 212 haplogroups. TK groups are more genetically homogeneous than AA groups, with the latter exhibiting more ancient/basal mtDNA lineages, and showing more drift effects. Modeling of demic diffusion, cultural diffusion, and admixture scenarios consistently supports the spread of TK languages by demic diffusion. Surprisingly, there is significant genetic differentiation within ethnolinguistic groups, calling into question the common assumption that there is genetic homogeneity within ethnolinguistic groups.

Genetics↗

bioRxiv2015

Refining the Y chromosome phylogeny with southern African sequences

The recent availability of large-scale sequence data for the human Y chromosome has revolutionized analyses of and insights gained from this non-recombining, paternally inherited chromosome. However, the studies to date focus on Eurasian variation, and hence the diversity of early-diverging branches found in Africa has not been adequately documented. Here we analyze over 900 kb of Y chromosome sequence obtained from 547 individuals from southern African Khoisan and Bantuspeaking populations, identifying 232 new sequences from basal haplogroups A and B. We find new branches within haplogroups A2 and A3b1 and suggest that the prehistory of haplogroup B2a is more complex than previously suspected; this haplogroup is likely to have existed in Khoisan groups before the arrival of Bantu-speakers, who brought additional B2a lineages to southern Africa. Furthermore, we estimate older dates than obtained previously for both the A2-T node within the human Y chromosome phylogeny and for some individual haplogroups. Finally, there is pronounced variation in branch length between major haplogroups; haplogroups associated with Bantu-speakers have significantly longer branches. This likely reflects a combination of biases in the SNP calling process and demographic factors, such as an older average paternal age (hence a higher mutation rate), a higher effective population size, and/or a stronger effect of population expansion for Bantu-speakers than for Khoisan groups.

Evolutionary Biology↗

bioRxiv2015

Age-related and heteroplasmy-related variation in human mtDNA copy number

The mitochondrial (mt) genome is present in many copies in human cells, and intra-individual variation in mtDNA sequences is known as heteroplasmy. Recent studies found that heteroplasmies are highly tissue-specific, site-specific, and allele-specific, however the functional implications have not been explored. This study investigates variation in mtDNA copy numbers (mtCN) in 12 different tissues obtained at autopsy from 152 individuals (ranging in age from 3 days to 96 years). Three different methods to estimate mtCN were compared: shotgun sequencing (in 4 tissues), capture-enriched sequencing (in 12 tissues) and droplet digital PCR (ddPCR, in 2 tissues). The highest precision in mtCN estimation was achieved using shotgun sequencing data. However, capture-enrichment data provide reliable estimates of relative (albeit not absolute) mtCNs. Comparisons of mtCN from different tissues of the same individual revealed that mtCNs in different tissues are, with few exceptions, uncorrelated. Hence, each tissue of an individual seems to regulate mtCN in a tissue-related rather than an individual-dependent manner. Skeletal muscle (SM) samples showed an age-related decrease in mtCN that was especially pronounced in males, while there was an age-related increase in mtCN for liver (LIV) samples. MtCN in SM samples was significantly negatively correlated with both the total number of heteroplasmic sites and with minor allele frequency (MAF) at two heteroplasmic sites, 408 and 16327. Heteroplasmies at both sites are highly specific for SM, accumulate with aging and are part of functional elements that regulate mtDNA replication. These data support the hypothesis that selection acting on these heteroplasmic sites is reducing mtCN in SM of older individuals.\n\nAuthor SummaryThe total number of mitochondrial genomes in a human cell differs between individuals and between the tissues of a single individual; however the factors that influence this variation remain unknown. We estimated mtDNA copy number (mtCN) in 12 different tissues of 152 individuals applying three different methods, and found age-related variation for two tissues: mtCN in skeletal muscle is negatively correlated with age (especially in males) while mtCN in liver is positively correlated with age. Overall, mtCNs of different tissues within an individual are mainly independent of each other, indicating that tissue-specific rather than individual-specific processes largely influence mtCN.\n\nHeteroplasmy refers to intra-individual differences in the sequence of the mtDNA genome and heteroplasmic mutations accumulate during aging. Linear and partial regression analyses of mtCN with heteroplasmy (determined in a previous study of these same samples) revealed that the decrease of mtCN in skeletal muscle is mainly correlated with an increasing total number of heteroplasmic sites, and with increasing minor allele frequency at two sites (408 and 16327), that are heteroplasmic almost exclusively in skeletal muscle. As both sites are part of functional elements required for regulation of mtDNA replication, we suggest that selection may be acting via increasing heteroplasmy to reduce mtCN during aging.

Evolutionary Biology↗

bioRxiv2015

A Chronological Atlas of Natural Selection in the Human Genome during the Past Half-million Years

The spatiotemporal distribution of recent human adaptation is a long standing question. We developed a new coalescent-based method that collectively assigned human genome regions to modes of neutrality or to positive, negative, or balancing selection. Most importantly, the selection times were estimated for all positive selection signals, which ranged over the last half million years, penetrating the emergence of anatomically modern human (AMH). These selection time estimates were further supported by analyses of the genome sequences from three ancient AMHs and the Neanderthals. A series of brain function-related genes were found to carry signals of ancient selective sweeps, which may have defined the evolution of cognitive abilities either before Neanderthal divergence or during the emergence of AMH. Particularly, signals of brain evolution in AMH are strongly related to Alzheimers disease pathways. In conclusion, this study reports a chronological atlas of natural selection in Human.

Evolutionary Biology↗

bioRxiv2015

The complex admixture history and recent southern origins of Siberian populations

Although Siberia was inhabited by modern humans at an early stage, there is still debate over whether this area remained habitable during the extremely cold period of the Last Glacial Maximum or whether it was subsequently repopulated by peoples with a recent shared ancestry. Previous studies of the genetic history of Siberian populations were hampered by the extensive admixture that appears to have taken place among these populations, since commonly used methods assume a tree-like population history and at most single admixture events. We therefore developed a new method based on the covariance of ancestry components, which we validated with simulated data, in order to investigate this potentially complex admixture history and to distinguish the effects of shared ancestry from prehistoric migrations and contact. We furthermore adapted a previously devised method of admixture dating for use with multiple events of gene flow, and applied these methods to whole-genome genotype data from over 500 individuals belonging to 20 different Siberian ethnolinguistic groups. The results of these analyses indicate that there have indeed been multiple layers of admixture detectable in most of the Siberian populations, with considerable differences in the admixture histories of individual populations, and with the earliest events dated to not more than 4500 years ago. Furthermore, most of the populations of Siberia included here, even those settled far to the north, can be shown to have a southern origin. These results provide support for a recent population replacement in this region, with the northward expansions of different populations possibly being driven partly by the advent of pastoralism, especially reindeer domestication. These newly developed methods to analyse multiple admixture events should aid in the investigation of similarly complex population histories elsewhere.\n\nAuthor SummaryWe developed a new method that lets us disentangle complex admixture events and date the individual episodes of gene flow. We applied this method to a large dataset of genome-wide SNP genotypes from a linguistically diverse sample of populations covering the extent of Siberia. Our results demonstrate that these populations have been in intense contact with each other, with most of them carrying more than two, and up to six different ancestries. Nevertheless, as shown by the dates we estimate, these various admixture events have taken place over a relatively short time, with the oldest dating to not more than 4500 years ago. Our results emphasize the enormous impact that contact has had on the genetic history of these Siberian populations, and the methods developed here will be of use in the investigation of admixture events in populations around the world.

Genetics↗

bioRxiv2015

Denisovan Ancestry in East Eurasian and Native American Populations.

Although initial studies suggested that Denisovan ancestry was found only in modern human populations from island Southeast Asia and Oceania, more recent studies have suggested that Denisovan ancestry may be more widespread. However, the geographic extent of Denisovan ancestry has not been determined, and moreover the relationship between the Denisovan ancestry in Oceania and that elsewhere has not been studied. Here we analyze genome-wide SNP data from 2493 individuals from 221 worldwide populations, and show that there is a widespread signal of a very low level of Denisovan ancestry across Eastern Eurasian and Native American (EE/NA) populations. We also verify a higher level of Denisovan ancestry in Oceania than that in EE/NA; the Denisovan ancestry in Oceania is correlated with the amount of New Guinea ancestry, but not the amount of Australian ancestry, indicating that recent gene flow from New Guinea likely accounts for signals of Denisovan ancestry across Oceania. However, Denisovan ancestry in EE/NA populations is equally correlated with their New Guinea or their Australian ancestry, suggesting a common source for the Denisovan ancestry in EE/NA and Oceanian populations. Our results suggest that Denisovan ancestry in EE/NA is derived either from common ancestry with, or gene flow from, the common ancestor of New Guineans and Australians, indicating a more complex history involving East Eurasians and Oceanians than previously suspected.

Evolutionary Biology↗

bioRxiv2014

Evaluating intra- and inter-individual variation in the human placental transcriptome

BackgroundGene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta.\n\nResultsWe estimate that on average, 33.2%, 58.9% and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling and metabolism. Many biological traits demonstrated correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome (65% of expressed genes) exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection (26%), directional selection (4.9%), or diversifying selection (4.8%).\n\nConclusionWe apportion placental gene expression variation into individual, population and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.

Genomics↗

bioRxiv2014

Reconstructing Austronesian population history in Island Southeast Asia

Austronesian languages are spread across half the globe, from Easter Island to Madagascar. Evidence from linguistics and archaeology indicates that the \"Austronesian expansion,\" which began 4-5 thousand years ago, likely had roots in Taiwan, but the ancestry of present-day Austronesian-speaking populations remains controversial. Here, focusing primarily on Island Southeast Asia, we analyze genome-wide data from 56 populations using new methods for tracing ancestral gene flow. We show that all sampled Austronesian groups harbor ancestry that is more closely related to aboriginal Taiwanese than to any present-day mainland population. Surprisingly, western Island Southeast Asian populations have also inherited ancestry from a source nested within the variation of present-day populations speaking Austro-Asiatic languages, which have historically been nearly exclusive to the mainland. Thus, either there was once a substantial Austro-Asiatic presence in Island Southeast Asia, or Austronesian speakers migrated to and through the mainland, admixing there before continuing to western Indonesia.

Genetics↗

bioRxiv2014

Migration and interaction in a contact zone: mtDNA variation among Bantu-speakers in southern Africa

Bantu speech communities expanded over large parts of sub-Saharan Africa within the last 4000-5000 years, reaching different parts of southern Africa 1200-2000 years ago. The Bantu languages subdivide in several major branches, with languages belonging to the Eastern and Western Bantu branches spreading over large parts of Central, Eastern, and Southern Africa. There is still debate whether this linguistic divide is correlated with a genetic distinction between Eastern and Western Bantu speakers. During their expansion, Bantu speakers would have come into contact with diverse local populations, such as the Khoisan hunter-gatherers and pastoralists of southern Africa, with whom they may have intermarried. In this study, we analyze complete mtDNA genome sequences from over 900 Bantu-speaking individuals from Angola, Zambia, Namibia, and Botswana to investigate the demographic processes at play during the last stages of the Bantu expansion. Our results show that most of these Bantu-speaking populations are genetically very homogenous, with no genetic division between speakers of Eastern and Western Bantu languages. Most of the mtDNA diversity in our dataset is due to different degrees of admixture with autochthonous populations. Only the pastoralist Himba and Herero stand out due to high frequencies of particular L3f and L3d lineages; the latter are also found in the neighboring Damara, who speak a Khoisan language and were foragers and small-stock herders. In contrast, the close cultural and linguistic relatives of the Herero and Himba, the Kuvale, are genetically similar to other Bantu-speakers. Nevertheless, as demonstrated by resampling tests, the genetic divergence of Herero, Himba, and Kuvale is compatible with a common shared ancestry with high levels of drift and differential female admixture with local pre-Bantu populations.

Evolutionary Biology↗

bioRxiv2014

Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences

To investigate in detail the paternal and maternal demographic histories of humans, we obtained [~]500 kb of non-recombining Y chromosome (NRY) sequences and complete mtDNA genome sequences from 623 males from 51 populations in the CEPH Human Genome Diversity Panel (HGDP). Our results: confirm the controversial assertion that genetic differences between human populations on a global scale are bigger for the NRY than for mtDNA; suggest very small ancestral effective population sizes (<100) for the out-of-Africa migration as well as for many human populations; and indicate that the ratio of female effective population size to male effective population size (Nf/Nm) has been greater than one throughout the history of modern humans, and has recently increased due to faster growth in Nf. However, we also find substantial differences in patterns of mtDNA vs. NRY variation in different regional groups; thus, global patterns of variation are not necessarily representative of specific geographic regions.

Genetics↗