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首页> 外文期刊>Movement disorders >Reaping what you sow: Cross-seeding between aggregation-prone proteins in neurodegeneration.
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Reaping what you sow: Cross-seeding between aggregation-prone proteins in neurodegeneration.

机译:收获:在神经退行性病变中易于聚集的蛋白质之间进行交叉播种。

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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.
机译:由于可用于研究的SNP的收集存在严重偏差,因此尚未充分探索MSY系统发育的最深节点的序列多样性和年龄。我们通过高覆盖率的下一代测序技术对全球68条Y染色体进行了鉴定,其中包括18个根深蒂固的Y染色体,并鉴定了2386个SNP,其中80%是新颖的。该变体库的许多方面类似于在全基因组从头事件中观察到的模式,这表明在MSY中,很大一部分新出现的等位基因在系统发育中幸存下来。某种程度的纯化选择以过量的私人错义变体形式出现。我们的树概括了以前已知的拓扑,但是主要分支的相对长度已被大大修改,并且相关的节点年龄明显更长。当比较罕见的深根A1b非洲血统与树的其余部分时,我们发现明显不同的分支长度。我们的测年结果和系统地理学得出以下主要结论:(1)年龄接近早期AMH化石的父系世系今天仅在中西部非洲生存; (2)只有少数进化成功的MSY谱系在160至115 kya之间幸存; (3)应考虑适合最近的西亚考古学证据的提前退出非洲(70 kya之前)。我们的实验设计产生了无偏倚的新MSY标记资源,可为解剖学上现代的人类基因库的初始形成提供信息,即,我们进化的时期以前被认为是父系遗传标记难以接近的。

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