Finding genes that determine variation in sperm morphology and motility

在不同的动物类群中，精子可能是所有类型细胞中最多样化的。然而，在所有物种中，它们都有一个主要功能：使卵子受精。在许多不同的生物学和医学分支学科中，人们对精子形态如何影响精子的活力(游泳速度)和生育能力有相当大的兴趣。我们可能都有这样一个卡通形象：尾巴最长的精子游得比尾巴短的精子快。因此，也许令人惊讶的是，在人们研究精子长度和精子活力之间关系的大多数生物体中，他们要么没有找到任何关系，要么只发现了与精子的特定组成部分(例如头部、中段)的关系。斑马雀是神经生物学和行为生态学的重要模式生物，在我们的研究中，我们发现，在雄性之间，精子特征有相当大的差异，但在雄性体内，精子的形态和运动能力具有高度的可重复性。我们还证明，精子长的男性精子最快，精子长度和精子速度都是可遗传的。最后(也是独一无二的)，我们发现精子长度和精子活动率之间存在遗传相关性，这强烈表明这种关系是因果关系，而不是因为这两个精子特征同时受到环境因素(如饮食、条件)的影响。在研究斑马雀精子生物学的同时，我们也一直走在斑马雀基因组学工具开发的前沿。例如，我们构建了第一个斑马雀遗传连锁图谱，我们是一个国际团队的成员，该团队对斑马雀基因组进行了测序和组装。在这个项目中，我们将整合我们之前斑马雀工作的两条链(精子生物学和基因组学)。我们将进行全基因组关联研究，以定位和识别导致男性间精子形态和活力差异的基因。目前还没有在任何物种中发现导致精子活力差异的基因。我们将开发一种芯片，一次探测20,000个遗传标记，并用该芯片对1000只雄鸟(具有已知精子形态/活力)进行分型。我们还将从20名精子较短的男性和20名精子较长的男性的睾丸中对转录组(包含编码蛋白质的基因组部分)进行测序。这些雄性来自我们现有的选育系，这些选系已经显示出精子长度的巨大差异。通过整合GWAs和转录组数据，我们将首次描述决定精子形态和活力变异的基因。因此，我们的发现将与人类生育医学、动物育种/农业、保护生物学和进化生物学的研究人员相关。

Across different animal taxa, sperm are perhaps the most diverse of all types of cell. However, in all species they have one principal function; to fertilise an egg. In many different biological and medical sub-disciplines there has been considerable interest in how sperm morphology can influence sperm motility (swimming speed) and fertility. We probably all have a 'cartoon' image of sperm with the longest tail swimming faster than sperm with short tails. Therefore, it is perhaps surprising that within most organisms where people have looked at the relationship between sperm length and sperm motility they have either failed to find any relationship, or have only found a relationship with particular components of the sperm (e.g. the head, the midpiece). In our study organism, the zebra finch, which is an important model organism in neurobiology and behavioural ecology, we have shown that there is considerable inter-male variation in sperm traits, but that within males sperm morphology and motility are highly repeatable. We have also demonstrated that males with long sperm have the fastest sperm, and that both sperm length and sperm speed are heritable. Finally (and uniquely) we have shown that there is a genetic correlation between sperm length and sperm motility, which strongly suggests that the relationship is causative rather than because both sperm traits are simultaneously influenced by environmental factors (e.g. diet, condition). While investigating zebra finch sperm biology we have also been at the forefront of the development of zebra finch genomics tools. For example, we constructed the first zebra finch genetic linkage map and we were part of an international team that sequenced and assembled the zebra finch genome. In this project we will integrate the two strands (sperm biology and genomics) of our previous zebra finch work. We will perform genome-wide association studies (GWAS) to map and identify the genes responsible for inter-male differences in sperm morphology and motility. Genes responsible for differences in sperm motility have not yet been identified in any species. We will do this by developing a chip that probes 20,000 genetic markers at once and typing 1000 male birds (of known sperm morphology/motility) with the chip. We will also sequence the transcriptome (which contains the part of the genome that encodes proteins) from the testes of 20 males with short sperm and 20 males with long sperm. These males come from our existing selection lines which already show a large difference in sperm length. By integrating the GWAS and the transcriptomics data we will provide the first ever description of the genes that determine variation in sperm morphology and motility. Therefore, our findings will be relevant to researchers in human fertility medicine, animal breeding/agriculture, conservation biology and evolutionary biology.