Bilateral BBSRC-FAPESP: The genetic architecture and evolution of pleiotropy associated with evolutionary changes in developmental trajectories

了解基因组如何使我们在个体中观察到的特征（即，它们的“表型”）也许是生物学中最基本的问题。实现这样的理解一直具有挑战性，因为从基因组到我们观察到的性状有许多途径，这些性状本身可能是复杂的和“多维的”，由一系列性状组成，这些性状通过由共享基因组控制的共同发育过程联系在一起。共同的基因组和发育基础通常有助于性状之间的关联，其中一个性状的表达与其他性状的表达相关。性状之间的这种关联在进化过程中起着重要作用，因为它们使一个性状的进化命运与其他性状的命运联系在一起。此外，个人的成功（即，他们的“达尔文适应性”（Darwinian fitness）是他们所有特征的产物，协调一致地运作，因此自然选择可以偏爱特定的特征组合，从而塑造特征之间的关系。我们建议研究的遗传基础和这些性状之间的关联的进化，通过研究种群的小鼠，已经演变的差异，在其增长模式，以响应人工选择（选择性育种不同的增长模式）。我们关注的八个种群是由四种不同的人工选择模式产生的，这些模式改变了它们在出生后发育早期和晚期的生长速度。这导致了一系列新的生长模式，早期和晚期生长之间的关系与起始代中的模式不同。为了了解选择如何改变生长性状之间的关系，以及这些发育变化如何反过来改变成年性状发育终点的变异性质，我们将混合这八个选择系的种群基因组。使用这个混合种群，我们将问“如何从这些进化上不同的种群中继承基因组区域，使生长模式通过选择而被‘重塑’？”'.我们将研究这些基因组区域如何“映射”到表型的整体模式（即，它们如何影响个体表达的性状的总体模式）以及基因组区域之间的复杂相互作用，这些区域共同决定了复杂的成人表型中的生长模式和变异模式。我们也会问“母体特征的变化在改变后代的生长模式中扮演了什么角色？”'.我们已经知道母亲影响后代生长的方式发生了变化，但我们不知道这些母亲影响的变化是否导致了选择倾向的进化变化，或者它们是否导致了与选择倾向相反的“适应不良”变化。我们将整合我们积累的关于基因组如何构建我们观察到的性状的所有信息，以更好地理解进化如何在分子水平上进行，以及这些遗传变化如何允许选择重塑生长和发育模式。然后，我们将把这些发育变化与成年人发育过程中产生的变异模式联系起来，以了解不断变化的生长模式如何影响发育过程中产生的遗传变异模式。

Understanding how the genome makes the traits we observe in individuals (i.e., their 'phenotype') is perhaps the most fundamental problem in biology. Achieving such an understanding has been challenging because there are many pathways from the genome to the traits we observe, and those traits themselves can be complex and 'multidimensional', being made up of suites of traits that are tied together through the shared process of development controlled by a shared genome. The shared genomic and developmental bases generally contribute to associations between traits, where the expression of one trait is correlated to the expression of other traits. Such associations between traits play a major role in evolutionary processes because they make the evolutionary fate of one trait tied to the fate of other traits. Furthermore, the success of an individual (i.e., their 'Darwinian fitness') is a product of all of their traits, operating in concert, and hence natural selection can favour particular combinations of traits and thereby shape the relationship between traits. We propose to examine the genetic basis and evolution of these associations between traits by studying populations of mice that have evolved differences in their patterns of growth in response to artificial selection (selective breeding for different growth patterns). The eight populations we are focusing on were generated by four different patterns of artificial selection that altered their rate of growth early and late in postnatal development. This resulted in a series of growth patterns that are novel and the relationship between early and late growth is different to the pattern seen in the starting generation. To understand how selection has changed the relationship between growth traits, and how these changes in development, in turn, alter the nature of variation seen at the endpoint of development in adult traits, we will mix the genomes of populations from these eight selection lines. Using this mixed population, we will ask 'how having inherited regions of the genome from these evolutionarily divergent populations allowed patterns of growth to become 'reshaped' by selection?'. We will look at the overall patterns of how these genomic regions 'map' to phenotypes (i.e., how they influence the overall pattern of traits expressed by individuals) as well as complex interactions between regions of the genome that together determine the pattern of growth and patterns of variation in complex adult phenotypes. We will also ask 'what role have changes in maternal traits played in altering patterns of growth in their offspring?'. We already know that something has changed in the way that mothers influence the growth of their offspring, but we do not know whether changes in these maternal influences led to evolutionary changes in the direction favoured by selection or whether they contributed 'maladaptive' changes opposing the direction favoured by selection. We will integrate all of the information we accumulate on how genomes build the traits we observe to develop a better understanding of how evolution proceeds at the molecular level, and how these genetic changes allowed selection to reshape patterns of growth and development. We will then link these developmental changes to the patterns of variation produced as the output of development in adults to understand how shifting growth patterns impacts the patterns of genetic variation that are produced as the output of the developmental process.