Tapeworm loses its telomeres

一个完全解决,chromosome-level基因组组装of a tapeworm provides thefirst complete picture在动物生命的三个主要分支之一的代表中,Lophotrochozoa提供了不含抽样误差的资源,并揭示了对染色体进化的意外见解。

tape虫是所有类别的脊椎动物的无处不在寄生虫,并且具有复杂的生命周期,通常涉及至少一个无脊椎动物中间宿主和一个脊椎动物的最终宿主,其中成人,分段的蠕虫位于肠系统中。当我们扮演中间宿主的角色时,人类感染最严重,获得了tape虫的幼虫形式,该形式通常与中枢神经系统相关联肠系统外部。例如,人类感染“猪肉”的幼虫taenia soliumis estimated to be responsible for a third of cases of epilepsy in Latin America.

Although such species are important to investigate, their life cycles cannot be practically maintained in the laboratory and hence much of our fundamental understanding of tapeworm biology is based instead on species with life cycles involving beetles and rodents, as such hosts are themselves used as laboratory models.

Sanger Institute寄生虫基因组学群体领导的寄生虫基因组的表征是我们努力征服这些病原体引起的慢性疾病的最重要的全球进步。在大约十年的时间里,已经表征了最重要的扁虫物种(即platyhelminths)和round虫(即线虫)寄生虫的基因组,并且可以免费提供数据。

Some of these genomes have now been assembled to the level of complete chromosomes, allowing investigation not only of genome content but also of the genetic landscape arrayed along their chromosomes. One of these is the mouse bile-duct tapeworm,Hymenolepis microstoma,一个重要的实验室模型,基因组草案是published in 2013

Getting it together

The first genome level sequencing technologies were based on a divide and conquer approach: the genome is fragmented into millions of short (100s of bases) pieces which are then sequenced in parallel, generating millions of short ‘reads’ that must be assembled on a computer. While these technologies are sufficient in terms of covering all or most of the bases, short reads are problematic to assemble, as repetitive and low complexity sequences in the genome mean that many reads cannot be unambiguously aligned to single positions.

As a result, most characterised genomes to date are still made up of far more un-assembled fragments of sequence than the number of chromosomes the organism has, obscuring their syntenic relationships (i.e. the relative positions of the various genetic elements).

最新的技术允许对长读数进行测序 - 很长的读取 - 生成数十万到数百万个基础的连续序列,而免费方法(如光学映射)(一种基于基于序列的方法来物理映射染色体片段的相对位置))提供其他证据以帮助高级组装。这些技术用于改变基因组草案Hmicrostomainto a fully assembled, chromosome-level reference genome – the first entirely resolved genome of a representative of the Lophotrochozoa: the great animal group encompassing molluscs, annelids, flatworms and a diverse array of smaller phyla of invertebrate animals.

垃圾最重要

A fully characterised and assembled genome is invaluable in research for many reasons, not least because it is free from sampling error (e.g. is a gene really missing, or has the genome been incompletely characterised?). Beyond the content of the genome, it also provides the opportunity to investigate its architecture: how the different elements of the genome – from the parts that code for proteins to those that represent genomic invaders – are arrayed along the different chromosomes (the longest contiguous stretches of a eukaryotic genome).

It has been known since the early days of sequencing of the human genome that much of it is comprised of short, non-coding sequence motifs. Initially known as ‘junk DNA’, their importance to genome evolution is still only starting to be appreciated. These sequences are the result of ‘transposable elements’ (TEs) which are bits of foreign, viral DNA that are incorporated into the genome and are variously removed or amplified in copy number through the course of evolution. All eukaryotic genomes investigated to date contain TEs, which can comprise over half of the genome in some species.

Today it is accepted that far from being junk, TEs are in fact responsible for some of the most significant aspects of genome evolution, such as gene duplication and reshuffling. But they are also responsible for the evolution of linear chromosomes themselves (a hallmark of eukaryotes) which are ‘capped’ (terminate) by short sequence motifs called telomeres. These 6 base sequence repeats act to maintain both the linearity and full lengths of chromosomes during replication.

同时,称为Centromere的更长(〜370个碱基)序列基序充当纺锤体附着的部位,使同源染色体在细胞分裂过程中隔离。Centromeres在TES中也具有其进化起源,尽管在TES的动态演化中矛盾地具有特异性的序列身份,尽管在有丝分裂中扮演了完全保守和基本作用。

Chromosomal FISH of telomere repeats. Both panels show chromosomal fluorescent in situ hybridisation using probes against the canonical telomere sequence (TTAGGGx7). Left: In haploid spermatozoa, only one focus is visible for each of the six chromosomes (arrows), whereas two foci per chromosome (= 12) would be expected if telomeric repeats were present on both ends. Right: Chromosomes (blue) of H. microstoma during mitosis when sister chromatids are still attached by their centromeres. Note a single telomeric array (pink) is detected at the opposing ends of each sister chromatid (arrows). (Photo credit: A Baillie).

Losing your telomeres

完整组装H. microstomagenome revealed that its chromosomes are capped by telomeres only on one end, whereas the opposing ends terminate instead with what turned out to be centromeric sequence arrays. Classically, the position of the centromere relative to the ends of chromosomes has been used as a means of describing a species ‘karyotype’. Those found to be near the ends of the chromosome are known as ‘telocentric’ (‘near the telomeres’) and, given the limited resolving abilities of karyological techniques, were assumed to nevertheless terminate in telomere sequence.

However, theH. microstoma基因组明确地表明,染色体确实可以终止在丝粒阵列中,大概是通过进化过程取代端粒的。

终端必须使丝粒扮演端粒在保护染色体末端的作用。同时,它还必须保持其作为细胞分裂期间纺锤体附着的底物的祖先作用。然而,扮演双重作用的发展远不及直截了当,因为有一些端粒特异性蛋白与端粒序列直接相互作用以维持染色体长度的稳态,并且这些可能还必须与Centromere序列基序相互作用。H. microstoma。This and other implications with respect to the underlying mechanisms that orchestrate these fundamental processes inH. microstoma需要进一步调查。同时,是否在用雌性中心核型描述的其他物种中发现了末端丝状,等待着其他基因组的完整组装。

Parasites are just organisms

即使在生物学家中,也很常见的是,将寄生虫视为与自由生活的动物完全分开,没有什么可以教给我们(最终)我们自己的生物学的人。同样徒劳地,其生物学中的任何新颖性通常都与他们的寄生生活方式有关。但是,寄生虫只是一种营养策略,在大多数主要有机体群体中至少有一些谱系所利用的策略。例如,很少有人会争辩说,我们从草食动物的研究中没有什么可学习的,而不是理解草食。这些发现在适用于所有生物体的染色体进化中的基本课程中,而不是“寄生虫”对基因组的影响。

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