Mixed peoples, mixed microbes: Human and Helicobacter pylori coevolution in the European-African population of Cape Verde

幽门螺杆菌(Hp)感染是世界上最常见的细菌感染之一，自大约10万年前起源于非洲以来，就一直与人类共同进化。正因为如此，来自世界各地的细菌和它们的宿主一样，在基因上是分层的。幽门螺杆菌有一个动态的基因组，随着宿主的选择压力而进化，表现出宿主内的基因组变异，这可能包括导致特定类型的毒力因子和组合的表达，并最终导致疾病。一些关于宿主内进化的研究表明，重组在幽门螺杆菌基因组多样化中发挥着关键作用，特别是在存在多个菌株感染的情况下。这些研究还表明，不同菌株的重组率是不同的。虽然这些研究才刚刚开始揭示幽门螺杆菌微进化的一般模式。该项目的目的是调查来自佛得角的人群中幽门螺杆菌的微进化模式，该人群来自欧洲和西非的混合血统。由于自第一次混合事件以来几代人发生的随机重组，佛得角目前的混合基因组(宿主基因组和惠普基因组)由具有欧洲和非洲血统的片段组成，相对容易通过计算进行追踪。我们可以利用这一性质来刻画惠普重组的历史及其在惠普多元化产生中的作用。其具体目的是描述来自80-100名受感染的佛得角人中每个人的最多5个细菌分离物的基因组变异，并利用这些数据根据非洲和欧洲血统的区块数量来推断分离物的单倍型结构(所谓的当地血统推断)，并评估混合和重组在佛得角总人口内和个人之间在产生细菌多样性方面的作用。

Helicobacter pylori (HP) infection is one of the most common bacterial infections in the world, and is known to have been co-evolving with humans since their origins in Africa ~100,000 years ago. Due to this, bacteria from around the world are genetically stratified as their hosts are. HP has a dynamic genome exhibiting intra-host genomic variation as it evolves in response to the selective pressures of the host, which can inclusively lead to the expression of specific types and combinations of virulence factors and ultimately disease. Several studies on within-host evolution showed the pivotal role of recombination in genomic diversification of HP, especially in the presence of infection with multiple strains. These studies have also shown that recombination rates are different among stains. Although these studies have only started to disclose general patterns of microevolution of HP. The aim of this project is to investigate the patterns of HP microevolution in a cohort from Cape Verde, a population that derives mixed ancestry from Europe and West Africa. Due to the random recombination that occurs over the generations since the first admixture event, present day admixed genomes (both host and HP genomes) in Cape Verde consist of mosaics of segments with European and African ancestry that are relatively easily to trace computationally. We can explore this property to characterize the history of recombination of HP and its role in the generation of diversification in HP. The specific aim is to characterize the genomic variation of up to 5 bacterial isolates from each of 80-100 infected Cape Verdeans and to use this data to infer the haplotypic structure of the isolates in terms of the number of blocks of African and European ancestry (so called inference of local ancestry), and to evaluate the role of admixture and recombination in generating bacterial diversity within and among individuals in the general population of Cape Verde.