Selection against archaic hominin genetic variation in regulatory regions.
Selection against archaic hominin genetic variation in regulatory regions.
复制标题
DOI：
10.1038/s41559-020-01284-0
复制
发表时间：
2020-11
影响因子：
16.8
通讯作者：
Harris K
中科院分区：
文献类型：
--
作者：
Telis N;Aguilar R;Harris K
尼安德特人和丹尼索瓦人 DNA 的痕迹仍然存在于现代人类基因库中，但已被基因和其他重要功能区域的自然选择系统地清除。这意味着许多古老的等位基因损害了杂交个体的健康，但人们对这种损害的本质知之甚少。在这里，我们发现增强子包含的尼安德特人和丹尼索瓦人变异比预期的要少，这表明选择作用是清除这些区域的古老等位基因，从而破坏了它们的基因调控功能。我们推断，选择主要作用于尼安德特人或丹尼索瓦人在与人类接触前不久出现的年轻古老变异。增强子并没有耗尽这两个古老物种中发现的旧变体。某些类型的增强子似乎比其他增强子更能耐受基因渗入。与组织特异性增强子相比，多效性增强子表现出更强的古老单核苷酸多态性消耗。在某种程度上，进化限制可以预测基因渗入消耗，但考虑到尼安德特人和丹尼索瓦人对新突变的相对耐受性，某些组织的增强子对尼安德特人和丹尼索瓦人等位基因的消耗比预期更多。胎儿大脑和肌肉是其增强子显示出最强烈的古老等位基因消耗的组织，但只有大脑增强子显示出异常严格的纯化选择的证据。我们的结论是，人类和古代等位基因之间的上位不相容性需要解释胎儿肌肉增强剂对古代变异的消耗程度，这可能是由于与人类相比，古代人类对更高肌肉质量的选择不同。
Traces of Neandertal and Denisovan DNA persist in the modern human gene pool, but have been systematically purged by natural selection from genes and other functionally important regions. This implies that many archaic alleles harmed the fitness of hybrid individuals, but the nature of this harm is poorly understood. Here, we show that enhancers contain less Neandertal and Denisovan variation than expected given the background selection they experience, suggesting that selection acted to purge these regions of archaic alleles that disrupted their gene regulatory functions. We infer that selection acted mainly on young archaic variation that arose in Neandertals or Denisovans shortly before their contact with humans; enhancers are not depleted of older variants found in both archaic species. Some types of enhancer appear to have tolerated introgression better than others; compared with tissue-specific enhancers, pleiotropic enhancers show stronger depletion of archaic single-nucleotide polymorphisms. To some extent, evolutionary constraint is predictive of introgression depletion, but certain tissues’ enhancers are more depleted of Neandertal and Denisovan alleles than expected given their comparative tolerance to new mutations. Foetal brain and muscle are the tissues whose enhancers show the strongest depletion of archaic alleles, but only brain enhancers show evidence of unusually stringent purifying selection. We conclude that epistatic incompatibilities between human and archaic alleles are needed to explain the degree of archaic variant depletion from foetal muscle enhancers, perhaps due to divergent selection for higher muscle mass in archaic hominins compared with humans.
登录
查看更多内容
影响因子：
64.8
作者：
Mallick, Swapan;Li, Heng;Lipson, Mark;Mathieson, Iain;Gymrek, Melissa;Racimo, Fernando;Zhao, Mengyao;Chennagiri, Niru;Nordenfelt, Susanne;Tandon, Arti;Skoglund, Pontus;Lazaridis, Iosif;Sankararaman, Sriram;Fu, Qiaomei;Rohland, Nadin;Renaud, Gabriel;Erlich, Yaniv;Willems, Thomas;Gallo, Carla;Spence, Jeffrey P.;Song, Yun S.;Poletti, Giovanni;Balloux, Francois;van Driem, George;de Knijff, Peter;Romero, Irene Gallego;Jha, Aashish R.;Behar, Doron M.;Bravi, Claudio M.;Capelli, Cristian;Hervig, Tor;Moreno-Estrada, Andres;Posukh, Olga L.;Balanovska, Elena;Balanovsky, Oleg;Karachanak-Yankova, Sena;Sahakyan, Hovhannes;Toncheva, Draga;Yepiskoposyan, Levon;Tyler-Smith, Chris;Xue, Yali;Abdullah, M. Syafiq;Ruiz-Linares, Andres;Beall, Cynthia M.;Di Rienzo, Anna;Jeong, Choongwon;Starikovskaya, Elena B.;Metspalu, Ene;Parik, Juri;Villems, Richard;Henn, Brenna M.;Hodoglugil, Ugur;Mahley, Robert;Sajantila, Antti;Stamatoyannopoulos, George;Wee, Joseph T. S.;Khusainova, Rita;Khusnutdinova, Elza;Litvinov, Sergey;Ayodo, George;Comas, David;Hammer, Michael F.;Kivisild, Toomas;Klitz, William;Winkler, Cheryl A.;Labuda, Damian;Bamshad, Michael;Jorde, Lynn B.;Tishkoff, Sarah A.;Watkins, W. Scott;Metspalu, Mait;Dryomov, Stanislav;Sukernik, Rem;Singh, Lalji;Thangaraj, Kumarasamy;Paeaebo, Svante;Kelso, Janet;Patterson, Nick;Reich, David
通讯作者：
Reich, David
影响因子：
64.5
作者：
Long, Hannah K.;Prescott, Sara L.;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
64.5
作者：
Browning SR;Browning BL;Zhou Y;Tucci S;Akey JM
通讯作者：
Akey JM
影响因子：
12.3
作者：
Dannemann M;Prüfer K;Kelso J
通讯作者：
Kelso J
影响因子：
7
作者：
Coolon JD;McManus CJ;Stevenson KR;Graveley BR;Wittkopp PJ
通讯作者：
Wittkopp PJ