Signatures of hybridization in Trypanosoma brucei.
Signatures of hybridization in Trypanosoma brucei.
复制标题
DOI：
10.1371/journal.ppat.1010300
复制
发表时间：
2022-03
期刊：
影响因子：
6.7
通讯作者：
Gibson W
中科院分区：
文献类型：
--
作者：
Kay C;Peacock L;Williams TA;Gibson W
致病微生物之间的遗传交换可以产生联合收割机结合不同致病性状的后代。虽然有性生殖已被描述在锥虫，其对人类非洲锥虫（HAT）的流行病学的影响仍然存在争议。然而，人类感染性和非人类感染性布氏锥虫菌株在撒哈拉以南非洲HAT流行地区以相同的传播周期传播，为采采蝇媒介的发育周期提供了交配机会。在这里，我们研究了遗传之间的后代从一个实验室杂交T。然后将这些见解应用于实地收集的分离株的基因组分析，以确定过去遗传交换的特征。两个亲本和四个杂交后代克隆的基因组与一系列的DNA含量进行组装和分析的k-mer和单核苷酸多态性（SNP）的频率，以确定杂合性和染色体遗传。从每个基因组中提取变异表面糖蛋白（VSG）基因和动基体（线粒体）DNA大环和小环，以检查这些组分中的每一个如何在杂交后代中遗传。同样的生物信息学方法应用于另外37个代表T.在撒哈拉以南的非洲和T. evansi SNP分析提供了影响所有11对巨染色体的交叉事件的证据，并证明多倍体杂种是在减数分裂后形成的，而不是通过亲本二倍体细胞的融合。VSGs和动基体DNA微环是双亲遗传的，每个父母的数量大致相等，而大环是单亲遗传的。这些结果外推到外地分离株，使我们能够区分克隆血统杂交比较maxicircle基因型VSG和minicircle剧目。大环基因型和VSG和小环库之间的不一致表明谱系间杂交。值得注意的是，我们发现的一些杂交事件涉及在同一地理区域传播的人类感染性和非人类感染性锥虫。有性生殖允许不同个体的基因在后代中混合。这对致病微生物尤其重要，因为有害性状的新组合可能会出现，可能导致更严重的疾病爆发。采采蝇传播的锥虫是单细胞寄生虫，在热带非洲引起严重的人类和牲畜疾病。在采采蝇的发育周期中，锥虫可以交配并产生杂交锥虫，其具有来自每个亲本的一套染色体。但也经常观察到多倍体杂种，它们具有来自一个或两个亲本的一套以上染色体。在这里，我们已经调查了这些多倍体杂种是如何形成的，通过比较杂交后代的基因组与他们的父母。对二倍体和多倍体杂种的大的成对染色体的分析表明频繁的交换，这是减数分裂的标志，减数分裂是产生单倍体配子的特殊分裂形式。这表明多倍体是在减数分裂后形成的，而不是通过亲本二倍体细胞的融合形成的。我们还研究了锥虫的其他两个特征的遗传：变异表面糖蛋白（VSG）基因的大家族和线粒体（动基体）DNA。杂交克隆从每个亲本中继承了大约一半的VSG基因，并且还显示了动基体DNA的一个组成部分小环的双亲遗传。我们通过比较它们的VSG和小环库以及大环基因型来评估实地收集的锥虫的相关性。虽然大多数分离株共享很少的VSG或小环，但来自乌干达的一组主要感染人类的菌株有很大比例的共同谱。大多数这些锥虫可能是相关的克隆下降，但我们也确定了一些杂交的不匹配之间的maxicircle基因型和VSG和minicircle剧目。这些杂交信号也在其他一些野外采集的分离株中检测到，表明遗传交换在自然界中广泛存在。值得注意的是，杂交事件涉及在相同地理区域中循环的人类感染性和非人类感染性锥虫，提供了产生新的、可能更具致病性的锥虫菌株的机制，从而引起人类疾病。
Genetic exchange among disease-causing micro-organisms can generate progeny that combine different pathogenic traits. Though sexual reproduction has been described in trypanosomes, its impact on the epidemiology of Human African Trypanosomiasis (HAT) remains controversial. However, human infective and non-human infective strains of Trypanosoma brucei circulate in the same transmission cycles in HAT endemic areas in subsaharan Africa, providing the opportunity for mating during the developmental cycle in the tsetse fly vector. Here we investigated inheritance among progeny from a laboratory cross of T. brucei and then applied these insights to genomic analysis of field-collected isolates to identify signatures of past genetic exchange. Genomes of two parental and four hybrid progeny clones with a range of DNA contents were assembled and analysed by k-mer and single nucleotide polymorphism (SNP) frequencies to determine heterozygosity and chromosomal inheritance. Variant surface glycoprotein (VSG) genes and kinetoplast (mitochondrial) DNA maxi- and minicircles were extracted from each genome to examine how each of these components was inherited in the hybrid progeny. The same bioinformatic approaches were applied to an additional 37 genomes representing the diversity of T. brucei in subsaharan Africa and T. evansi. SNP analysis provided evidence of crossover events affecting all 11 pairs of megabase chromosomes and demonstrated that polyploid hybrids were formed post-meiotically and not by fusion of the parental diploid cells. VSGs and kinetoplast DNA minicircles were inherited biparentally, with approximately equal numbers from each parent, whereas maxicircles were inherited uniparentally. Extrapolation of these findings to field isolates allowed us to distinguish clonal descent from hybridization by comparing maxicircle genotype to VSG and minicircle repertoires. Discordance between maxicircle genotype and VSG and minicircle repertoires indicated inter-lineage hybridization. Significantly, some of the hybridization events we identified involved human infective and non-human infective trypanosomes circulating in the same geographic areas. Sexual reproduction allows genes from different individuals to be mixed up in the offspring. This is particularly important for disease-causing microbes, because new combinations of harmful traits can arise, potentially leading to more severe outbreaks of disease. Tsetse-transmitted trypanosomes are single-celled parasites that cause severe human and livestock diseases in tropical Africa. During their developmental cycle in the tsetse fly, trypanosomes can mate and produce hybrid trypanosomes, which have one set of chromosomes from each parent. But polyploid hybrids, with more than one set of chromosomes from one or both parents, are often observed too. Here we have investigated how these polyploid hybrids are formed by comparing the genomes of hybrid progeny with those of their parents. Analysis of the large, paired chromosomes of both diploid and polyploid hybrids showed frequent crossovers, which are the hallmark of meiosis, the special form of division that produces haploid gametes. This indicates that the polyploids were formed after meiosis rather than by fusion of the parental diploid cells. We also investigated the inheritance of two other features of trypanosomes: the large family of variant surface glycoprotein (VSG) genes, and the mitochondrial (kinetoplast) DNA. Hybrid clones had inherited about half the VSG genes from each parent, and also showed biparental inheritance of one component of the kinetoplast DNA, the minicircles. We assessed the relatedness of field-collected trypanosomes by comparing their VSG and minicircle repertoires, together with maxicircle genotype. While most isolates shared few VSGs or minicircles, a group of mostly human-infective strains from Uganda had a large proportion of their repertoires in common. Most of these trypanosomes were probably related by clonal descent, but we also identified that some were hybrids by the mismatch between their maxicircle genotype and their VSG and minicircle repertoires. These signals of hybridization were also detected in some of the other field-collected isolates, suggesting that genetic exchange is widespread in nature. Significantly, the hybridization events involved human infective and non-human infective trypanosomes circulating in the same geographic areas, providing a mechanism for the generation of new, potentially more pathogenic, trypanosome strains causing human disease.
登录
查看更多内容
影响因子：
64.8
作者：
Gaunt, MW;Yeo, M;Miles, MA
通讯作者：
Miles, MA
DOI：
10.1016/0169-4758(86)90011-6
发表时间：
1986-01-01
期刊：
Parasitology Today
影响因子：
--
作者：
GIBSON W C
通讯作者：
GIBSON W C
DOI：
10.1099/00221287-143-3-909
发表时间：
1997-03-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Gibson, W;Winters, K;Bailey, M
通讯作者：
Bailey, M
DOI：
10.1126/science.1169464
发表时间：
2009-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Akopyants NS;Kimblin N;Secundino N;Patrick R;Peters N;Lawyer P;Dobson DE;Beverley SM;Sacks DL
通讯作者：
Sacks DL
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.