内容提要：
The mammalian genome is 1% coding and 99% dark-matter, with that 99% controlling how the 1% is expressed. In primates, the loss of the tail in humans and apes is a major evolutionary change that may have helped with bipedalism. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. We provide compelling evidence that an Alu element insertion in the hominoid ancestor likely led to tail loss. We demonstrate that this Alu element-inserted into an intron of the TBXT gene-pairs with a neighboring ancestral Alu element to induce a hominoid-specific alternative splicing event. In mouse models, this splicing resulted in either no tail or a shortened tail. Additionally, our results suggest that losing the tail may come with an adaptive cost, leading to potential health issues like neural tube defects.
Moreover, I will talk about our technology development for studying the non-coding regulatory elements, focusing on 3D genome organization. Traditional genetic screen typically requires a large-scale experimental setup, which is limited by the available resource and experimental feasibility. To solve this challenge, we recently proposed and developed an in silico genetic screen (ISGS) approach to study 3D genome, building on predictive AI model. From model development to the fundamental discoveries, I will talk about how in silico genetic screen approaches can accelerate our discoveries in genome regulation, and how this approach can be used in both normal and disease-related biological systems.
讲者简介：
夏波，麻省理工学院-哈佛大学博德研究所（Broad Institute）PI，哈佛大学哈佛学会青年学者（Junior Fellow of the Society of Fellows）。夏波实验室旨在理解基因组调控的基本规律和机制，从而理解生命过程中细胞命运决定的机制并开发新的细胞功能调控手段。夏波博士早期在北京大学伊成器教授实验室担任本科生研究助理，期间领导并开发了一系列用于分析表观基因组的化学技术。2022年获得纽约大学医学院博士学位，师从Itai Yanai教授和Jef D. Boeke教授。期间开创了多项关于基因组调控及其对人类发育和演化影响的创新研究，包括揭示人类和猿类尾巴消失的遗传基础。夏波博士的文章主要发表于Nature Methods (2015)、Cell Stem Cell (2017)、Cell (2020, cover)、Nature Biotechnology (2023)、Nature (2024, cover)、Med (2024, cover)等。夏波博士曾荣获多个重要奖项，包括2020年Regeneron创新奖、2022年Harold M. Weintraub研究生奖、2022年国家自费留学生奖-特别优秀奖、2024年MIT Technology Review Innovator Under 35-Asia Pacific，以及NIH Director's Early Independence Award（DP5 award）等。
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