Convergent evolution of a genotoxic stress response in a parasite-specific p53 homolog.
Convergent evolution of a genotoxic stress response in a parasite-specific p53 homolog.
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DOI：
10.1073/pnas.2205201119
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发表时间：
2022-09-13
影响因子：
11.1
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中科院分区：
文献类型：
--
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P53是一种重要的肿瘤抑制因子，存在于所有后生动物中，包括不发生恶性肿瘤的无脊椎动物。关于为什么这些无脊椎动物拥有肿瘤抑制因子的流行理论是，P53最初是为了保护早期后生动物的种系免受遗传毒性应激（如紫外线辐射）而进化的。在这里，我们研究了两个P53同源物在寄生扁平虫曼氏血吸虫中的功能。第一个基因与典型P53同源，调控扁形虫干细胞的维持和分化。第二个P53基因是寄生虫特有的平行基因，是对基因毒性应激的正常反应所必需的。这种寄生虫特异性平行体的存在意味着寄生扁虫对基因毒性应激的反应能力可能来自趋同进化。P53是一种被广泛研究的肿瘤抑制因子，在细胞周期调节、细胞死亡和DNA损伤修复中发挥重要作用。P53在所有后生动物中都存在，甚至在没有恶性肿瘤的无脊椎动物中也存在。关于为什么这些无脊椎动物拥有肿瘤抑制因子的流行理论是，P53最初是为了保护早期后生动物的种系免受遗传毒性应激（如紫外线辐射）而进化的。这一理论主要是基于三种无脊椎动物的功能数据，忽略了包括扁虫在内的重要动物群体。先前对淡水涡虫地中海Schmidtea的研究表明，涡虫P53在干细胞维持和皮肤生成中起重要作用，但这些研究没有直接检测任何肿瘤抑制功能。为了更好地了解不同扁虫中P53同源物的功能，我们检测了两种不同P53同源物在寄生扁虫曼氏血吸虫中的功能。第一个P53同源物（P53 -1）与地中海S. P53（sme - P53）和人类TP53同源，调节扁形虫干细胞维持和皮肤生成。第二个P53同源物（P53 -2）是寄生虫特有的同源物，在寄生扁形虫中是保守的，是曼氏梭菌对基因毒性应激的正常反应所必需的。然后我们发现，在涡虫对基因毒性应激的反应中，smd -p53似乎没有发挥任何作用。寄生扁虫中这种具有肿瘤抑制样功能的寄生虫特异性平行体的存在表明，寄生扁虫对基因毒性应激的反应能力可能来自趋同进化。
P53 is an important tumor suppressor that is found throughout metazoans, including invertebrates that do not develop malignancies. The prevailing theory for why these invertebrates possess a tumor suppressor is that P53 originally evolved to protect the germline of early metazoans from genotoxic stress such as ultraviolet radiation. Here, we examine the function of two P53 homologs in the parasitic flatworm Schistosoma mansoni. The first is orthologous to canonical P53 and regulates flatworm stem cell maintenance and differentiation. The second P53 gene is a parasite-specific paralog that is required for the normal response to genotoxic stress. The existence of this parasite-specific paralog implies that the ability to respond to genotoxic stress in parasitic flatworms may have arisen from convergent evolution. P53 is a widely studied tumor suppressor that plays important roles in cell-cycle regulation, cell death, and DNA damage repair. P53 is found throughout metazoans, even in invertebrates that do not develop malignancies. The prevailing theory for why these invertebrates possess a tumor suppressor is that P53 originally evolved to protect the germline of early metazoans from genotoxic stress such as ultraviolet radiation. This theory is largely based upon functional data from only three invertebrates, omitting important groups of animals including flatworms. Previous studies in the freshwater planarian flatworm Schmidtea mediterranea suggested that flatworm P53 plays an important role in stem cell maintenance and skin production, but these studies did not directly test for any tumor suppressor functions. To better understand the function of P53 homologs across diverse flatworms, we examined the function of two different P53 homologs in the parasitic flatworm Schistosoma mansoni. The first P53 homolog (p53-1) is orthologous to S. mediterranea P53(Smed-p53) and human TP53 and regulates flatworm stem cell maintenance and skin production. The second P53 homolog (p53-2) is a parasite-specific paralog that is conserved across parasitic flatworms and is required for the normal response to genotoxic stress in S. mansoni. We then found that Smed-p53 does not seem to play any role in the planarian response to genotoxic stress. The existence of this parasite-specific paralog that bears a tumor suppressor–like function in parasitic flatworms implies that the ability to respond to genotoxic stress in parasitic flatworms may have arisen from convergent evolution.
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影响因子：
4.6
作者：
Pearson, Bret J.;Alvarado, Alejandro Sanchez
通讯作者：
Alvarado, Alejandro Sanchez
影响因子：
14.9
作者：
Blum M;Chang HY;Chuguransky S;Grego T;Kandasaamy S;Mitchell A;Nuka G;Paysan-Lafosse T;Qureshi M;Raj S;Richardson L;Salazar GA;Williams L;Bork P;Bridge A;Gough J;Haft DH;Letunic I;Marchler-Bauer A;Mi H;Natale DA;Necci M;Orengo CA;Pandurangan AP;Rivoire C;Sigrist CJA;Sillitoe I;Thanki N;Thomas PD;Tosatto SCE;Wu CH;Bateman A;Finn RD
通讯作者：
Finn RD
影响因子：
1.5
作者：
Howe KL;Bolt BJ;Shafie M;Kersey P;Berriman M
通讯作者：
Berriman M
影响因子：
14.9
作者：
Howe KL;Bolt BJ;Cain S;Chan J;Chen WJ;Davis P;Done J;Down T;Gao S;Grove C;Harris TW;Kishore R;Lee R;Lomax J;Li Y;Muller HM;Nakamura C;Nuin P;Paulini M;Raciti D;Schindelman G;Stanley E;Tuli MA;Van Auken K;Wang D;Wang X;Williams G;Wright A;Yook K;Berriman M;Kersey P;Schedl T;Stein L;Sternberg PW
通讯作者：
Sternberg PW
影响因子：
10.7
作者：
Darriba, Diego;Posada, David;Flouri, Tomas
通讯作者：
Flouri, Tomas