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

了解基因组如何形成我们在个体中观察到的特征（即他们的“表型”）可能是生物学中最基本的问题。实现这样的理解是具有挑战性的，因为从基因组到我们观察到的特征有许多途径，而这些特征本身可能是复杂的和“多维的”，由一系列特征组成，这些特征通过由共享基因组控制的共同发展过程联系在一起。共享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。性状之间的这种联系在进化过程中起着重要作用，因为它们使一种性状的进化命运与其他性状的命运联系在一起。此外，个体的成功（即他们的“达尔文适应度”）是他们所有特征协同工作的产物，因此自然选择可以倾向于特定的特征组合，从而塑造特征之间的关系。我们建议通过研究在人工选择（对不同生长模式的选择性育种）下进化出不同生长模式的小鼠种群，来研究这些性状之间关联的遗传基础和进化。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的早期和晚期的生长速度。这导致了一系列新颖的生长模式，早期和晚期生长之间的关系与开始一代的模式不同。为了理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，我们将混合来自这8个选择系的种群基因组。利用这个混合种群，我们将问“从这些进化上不同的种群中遗传基因组区域如何允许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”到表型的总体模式（即，它们如何影响个体表达的总体特征模式），以及基因组区域之间复杂的相互作用，这些区域共同决定了复杂成人表型的生长模式和变异模式。我们还会问“母性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一些变化，但我们不知道这些母亲影响的变化是否导致了有利于选择的进化方向的变化，或者它们是否导致了与选择有利的方向相反的“适应不良”变化。我们将整合我们所积累的关于基因组如何构建我们所观察到的特征的所有信息，以更好地理解进化是如何在分子水平上进行的，以及这些遗传变化是如何允许选择重塑生长和发育模式的。然后，我们将把这些发育变化与作为成人发育输出的变异模式联系起来，以了解生长模式的变化如何影响作为发育过程输出的遗传变异模式。

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.