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The timing and effect of the earliest human arrivals in North America 期刊论文
NATURE, 2020
作者:  Lorena Becerra-Valdivia;  Thomas Higham
收藏  |  浏览/下载:27/0  |  提交时间:2020/08/09

The peopling of the Americas marks a major expansion of humans across the planet. However, questions regarding the timing and mechanisms of this dispersal remain, and the previously accepted model (termed '  Clovis-first'  )-suggesting that the first inhabitants of the Americas were linked with the Clovis tradition, a complex marked by distinctive fluted lithic points(1)-has been effectively refuted. Here we analyse chronometric data from 42 North American and Beringian archaeological sites using a Bayesian age modelling approach, and use the resulting chronological framework to elucidate spatiotemporal patterns of human dispersal. We then integrate these patterns with the available genetic and climatic evidence. The data obtained show that humans were probably present before, during and immediately after the Last Glacial Maximum (about 26.5-19 thousand years ago)(2,3)but that more widespread occupation began during a period of abrupt warming, Greenland Interstadial 1 (about 14.7-12.9 thousand years beforead 2000)(4). We also identify the near-synchronous commencement of Beringian, Clovis and Western Stemmed cultural traditions, and an overlap of each with the last dates for the appearance of 18 now-extinct faunal genera. Our analysis suggests that the widespread expansion of humans through North America was a key factor in the extinction of large terrestrial mammals.


A Bayesian age model suggests that human dispersal to the Americas probably began before the Last Glacial Maximum, overlapping with the last dates of appearance for several faunal genera.


  
Ensuring meiotic DNA break formation in the mouse pseudoautosomal region 期刊论文
NATURE, 2020
作者:  Schuessler, R. X.;  Bekker, H.;  Brass, M.;  Cakir, H.;  Crespo Lopez-Urrutia, J. R.;  Door, M.;  Filianin, P.;  Harman, Z.;  Haverkort, M. W.;  Huang, W. J.;  Indelicato, P.;  Keitel, C. H.;  Koenig, C. M.;  Kromer, K.;  Mueller, M.;  Novikov, Y. N.;  Rischka, A.;  Schweiger, C.;  Sturm, S.;  Ulmer, S.;  Eliseev, S.;  Blaum, K.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

In mice, the pseudoautosomal region of the sex chromosomes undergoes a dynamic structural rearrangement to promote a high rate of DNA double-strand breaks and to ensure X-Y recombination.


Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation(1,2). How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its chromosome axes elongate and the sister chromatids separate. These processes are linked to heterochromatic mo-2 minisatellite arrays, and require MEI4 and ANKRD31 proteins but not the axis components REC8 or HORMAD1. We propose that the repetitive DNA sequence of the PAR confers unique chromatin and higher-order structures that are crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, notably, oocytes can be reprogrammed to exhibit spermatocyte-like levels of DSBs in the PAR simply by delaying or preventing synapsis. Thus, the sexually dimorphic behaviour of the PAR is in part a result of kinetic differences between the sexes in a race between the maturation of the PAR structure, formation of DSBs and completion of pairing and synapsis. Our findings establish a mechanistic paradigm for the recombination of sex chromosomes during meiosis.


  
Structure and mechanism of the mitochondrial Ca2+ uniporter holocomplex 期刊论文
NATURE, 2020
作者:  Kalaany, Nada Y.;  Sabatini, David M.
收藏  |  浏览/下载:21/0  |  提交时间:2020/07/03

Mitochondria take up Ca2+ through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca2+ signalling and cell death(1,2). In mammals, the uniporter complex (uniplex) contains four core components: the pore-forming MCU protein, the gatekeepers MICU1 and MICU2, and an auxiliary subunit, EMRE, essential for Ca2+ transport(3-8). To prevent detrimental Ca2+ overload, the activity of MCU must be tightly regulated by MICUs, which sense changes in cytosolic Ca2+ concentrations to switch MCU on and off(9,10). Here we report cryo-electron microscopic structures of the human mitochondrial calcium uniporter holocomplex in inhibited and Ca2+-activated states. These structures define the architecture of this multicomponent Ca2+-uptake machinery and reveal the gating mechanism by which MICUs control uniporter activity. Our work provides a framework for understanding regulated Ca2+ uptake in mitochondria, and could suggest ways of modulating uniporter activity to treat diseases related to mitochondrial Ca2+ overload.


Cryo-electron microscopy reveals the structures of the mitochondrial calcium uniporter holocomplex in low- and high-calcium conditions, showing the gating mechanism that underlies uniporter activation in response to intracellular calcium signals.


  
Skeleton of a Cretaceous mammal from Madagascar reflects long-term insularity 期刊论文
NATURE, 2020
作者:  Petit, L.;  Eenink, H. G. J.;  Russ, M.;  Lawrie, W. I. L.;  Hendrickx, N. W.;  Philips, S. G. J.;  Clarke, J. S.;  Vandersypen, L. M. K.;  Veldhorst, M.
收藏  |  浏览/下载:9/0  |  提交时间:2020/05/13

The fossil record of mammaliaforms (mammals and their closest relatives) of the Mesozoic era from the southern supercontinent Gondwana is far less extensive than that from its northern counterpart, Laurasia(1,2). Among Mesozoic mammaliaforms, Gondwanatheria is one of the most poorly known clades, previously represented by only a single cranium and isolated jaws and teeth(1-5). As a result, the anatomy, palaeobiology and phylogenetic relationships of gondwanatherians remain unclear. Here we report the discovery of an articulated and very well-preserved skeleton of a gondwanatherian of the latest age (72.1-66 million years ago) of the Cretaceous period from Madagascar that we assign to a new genus and species, Adalatherium hui. To our knowledge, the specimen is the most complete skeleton of a Gondwanan Mesozoic mammaliaform that has been found, and includes the only postcranial material and ascending ramus of the dentary known for any gondwanatherian. A phylogenetic analysis including the new taxon recovers Gondwanatheria as the sister group to Multituberculata. The skeleton, which represents one of the largest of the Gondwanan Mesozoic mammaliaforms, is particularly notable for exhibiting many unique features in combination with features that are convergent on those of therian mammals. This uniqueness is consistent with a lineage history for A. hui of isolation on Madagascar for more than 20 million years.


Adalatherium hui, a newly discovered gondwanatherian mammal from Madagascar dated to near the end of the Cretaceous period, shows features consistent with a long evolutionary trajectory of isolation in an insular environment.


  
Global conservation of species' niches 期刊论文
NATURE, 2020, 580 (7802) : 232-+
作者:  Guo, Xiaoyan;  Aviles, Giovanni;  Liu, Yi;  Tian, Ruilin;  Unger, Bret A.;  Lin, Yu-Hsiu T.;  Wiita, Arun P.;  Xu, Ke;  Correia, M. Almira;  Kampmann, Martin
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03

Environmental change is rapidly accelerating, and many species will need to adapt to survive(1). Ensuring that protected areas cover populations across a broad range of environmental conditions could safeguard the processes that lead to such adaptations(1-3). However, international conservation policies have largely neglected these considerations when setting targets for the expansion of protected areas(4). Here we show that-of 19,937 vertebrate species globally(5-8)-the representation of environmental conditions across their habitats in protected areas (hereafter, niche representation) is inadequate for 4,836 (93.1%) amphibian, 8,653 (89.5%) bird and 4,608 (90.9%) terrestrial mammal species. Expanding existing protected areas to cover these gaps would encompass 33.8% of the total land surface-exceeding the current target of 17% that has been adopted by governments. Priority locations for expanding the system of protected areas to improve niche representation occur in global biodiversity hotspots(9), including Colombia, Papua New Guinea, South Africa and southwest China, as well as across most of the major land masses of the Earth. Conversely, we also show that planning for the expansion of protected areas without explicitly considering environmental conditions would marginally reduce the land area required to 30.7%, but that this would lead to inadequate niche representation for 7,798 (39.1%) species. As the governments of the world prepare to renegotiate global conservation targets, policymakers have the opportunity to help to maintain the adaptive potential of species by considering niche representation within protected areas(1,2).


Protected areas would need to expand to 33.8% of the total land surface to adequately represent environmental conditions across the habitats of amphibians, birds and terrestrial mammals, far exceeding the current 17% target.


  
DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis 期刊论文
NATURE, 2020, 579 (7798) : 291-+
作者:  Avellaneda, Mario J.;  Franke, Kamila B.;  Sunderlikova, Vanda;  Bukau, Bernd;  Mogk, Axel;  Tans, Sander J.
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

The DNA-dependent protein kinase (DNA-PK), which comprises the KU heterodimer and a catalytic subunit (DNA-PKcs), is a classical non-homologous end-joining (cNHEJ) factor(1). KU binds to DNA ends, initiates cNHEJ, and recruits and activates DNA-PKcs. KU also binds to RNA, but the relevance of this interaction in mammals is unclear. Here we use mouse models to show that DNA-PK has an unexpected role in the biogenesis of ribosomal RNA (rRNA) and in haematopoiesis. The expression of kinase-dead DNA-PKcs abrogates cNHEJ(2). However, most mice that both expressed kinase-dead DNA-PKcs and lacked the tumour suppressor TP53 developed myeloid disease, whereas all other previously characterized mice deficient in both cNHEJ and TP53 expression succumbed to pro-B cell lymphoma(3). DNA-PK autophosphorylates DNA-PKcs, which is its best characterized substrate. Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice. KU drives the assembly of DNA-PKcs on a wide range of cellular RNAs, including the U3 small nucleolar RNA, which is essential for processing of 18S rRNA(4). U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609. DNA-PK, but not other cNHEJ factors, resides in nucleoli in an rRNA-dependent manner and is co-purified with the small subunit processome. Together our data show that DNA-PK has RNA-dependent, cNHEJ-independent functions during ribosome biogenesis that require the kinase activity of DNA-PKcs and its phosphorylation at the T2609 cluster.


  
Two conserved epigenetic regulators prevent healthy ageing 期刊论文
NATURE, 2020
作者:  Yoshida, Kenichi;  Gowers, Kate H. C.;  Lee-Six, Henry;  Chandrasekharan, Deepak P.;  Coorens, Tim;  Maughan, Elizabeth F.;  Beal, Kathryn;  Menzies, Andrew;  Millar, Fraser R.;  Anderson, Elizabeth;  Clarke, Sarah E.;  Pennycuick, Adam;  Thakrar, Ricky M.;  Butler, Colin R.;  Kakiuchi, Nobuyuki;  Hirano, Tomonori;  Hynds, Robert E.;  Stratton, Michael R.;  Martincorena, Inigo;  Janes, Sam M.;  Campbell, Peter J.
收藏  |  浏览/下载:34/0  |  提交时间:2020/07/03

It has long been assumed that lifespan and healthspan correlate strongly, yet the two can be clearly dissociated(1-6). Although there has been a global increase in human life expectancy, increasing longevity is rarely accompanied by an extended healthspan(4,7). Thus, understanding the origin of healthy behaviours in old people remains an important and challenging task. Here we report a conserved epigenetic mechanism underlying healthy ageing. Through genome-wide RNA-interference-based screening of genes that regulate behavioural deterioration in ageing Caenorhabditis elegans, we identify 59 genes as potential modulators of the rate of age-related behavioural deterioration. Among these modulators, we found that a neuronal epigenetic reader, BAZ-2, and a neuronal histone 3 lysine 9 methyltransferase, SET-6, accelerate behavioural deterioration in C. elegans by reducing mitochondrial function, repressing the expression of nuclear-encoded mitochondrial proteins. This mechanism is conserved in cultured mouse neurons and human cells. Examination of human databases(8,9) shows that expression of the human orthologues of these C. elegans regulators, BAZ2B and EHMT1, in the frontal cortex increases with age and correlates positively with the progression of Alzheimer'  s disease. Furthermore, ablation of Baz2b, the mouse orthologue of BAZ-2, attenuates age-dependent body-weight gain and prevents cognitive decline in ageing mice. Thus our genome-wide RNA-interference screen in C. elegans has unravelled conserved epigenetic negative regulators of ageing, suggesting possible ways to achieve healthy ageing.


Two epigenetic regulators-identified in an RNA interference screen in Caenhorhabditis elegans, and conserved in mammals-diminish mitochondrial function and accelerate the age-related deterioration of behaviour.


  
A claustrum in reptiles and its role in slow-wave sleep 期刊论文
NATURE, 2020, 578 (7795) : 413-+
作者:  Loubeyre, Paul;  Occelli, Florent;  Dumas, Paul
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

The mammalian claustrum, owing to its widespread connectivity with other forebrain structures, has been hypothesized to mediate functions that range from decision-making to consciousness(1). Here we report that a homologue of the claustrum, identified by single-cell transcriptomics and viral tracing of connectivity, also exists in a reptile-the Australian bearded dragon Pogona vitticeps. In Pogona, the claustrum underlies the generation of sharp waves during slow-wave sleep. The sharp waves, together with superimposed high-frequency ripples(2), propagate to the entire neighbouring pallial dorsal ventricular ridge (DVR). Unilateral or bilateral lesions of the claustrum suppress the production of sharp-wave ripples during slow-wave sleep in a unilateral or bilateral manner, respectively, but do not affect the regular and rapidly alternating sleep rhythm that is characteristic of sleep in this species(3). The claustrum is thus not involved in the generation of the sleep rhythm itself. Tract tracing revealed that the reptilian claustrum projects widely to a variety of forebrain areas, including the cortex, and that it receives converging inputs from, among others, areas of the mid- and hindbrain that are known to be involved in wake-sleep control in mammals(4-6). Periodically modulating the concentration of serotonin in the claustrum, for example, caused a matching modulation of sharp-wave production there and in the neighbouring DVR. Using transcriptomic approaches, we also identified a claustrum in the turtle Trachemys scripta, a distant reptilian relative of lizards. The claustrum is therefore an ancient structure that was probably already present in the brain of the common vertebrate ancestor of reptiles and mammals. It may have an important role in the control of brain states owing to the ascending input it receives from the mid- and hindbrain, its widespread projections to the forebrain and its role in sharp-wave generation during slow-wave sleep.


A structure homologous to the mammalian claustrum exists in reptiles and has a role in generating sharp waves in the brain during slow-wave sleep.