近年研究主題

適應性演化的分子機制、基因的序列空間

研究室簡介

生命的語言以A、T、G、C四個字母所構成,透過不同的排列組合及演化歷程, 這四個鹼基創造出功能多樣的基因群並交織成芸芸眾生的生命文本。生命的語言有幾種表述法?舉例來說,一串10個鹼基的DNA序列便有百萬種變化 (4^10 ~ 1,000,000),一條長度20個氨基酸的蛋白序列更有超越天文數字的可能 (20^20 ~ 100,000,000,000,000,000,000,000,000)!

這偌大的序列空間 (sequence space) 中究竟隱藏了多少種生物功能?是否存在功能相近但排列組合迥異的序列?為何有些序列賦予的功能專一,有些卻同時具有多種功用?我們能否找到自然界中不存在但具備創新特性的序列?

本實驗室以微生物及其基因為素材,運用遺傳工程、高通量基因選殖 (high-throughput screening/sequencing)、和實驗演化 (experimental evolution) 的手法探索良性突變的生理效應、代謝系統的演進過程、基因表現的起動機制、蛋白質多功性(promiscuity)的成因、和物種共同演化(coevolution)的分子基礎及交互作用。

<招募對象> 對演化生物學如癡如醉,想修習合成生物學的精妙武功,可左手拿pipette右手抓滑鼠的「奮」青。本團隊之研究議題很適合欲跨足生物領域之理工或資訊背景的同學發揮長才,如有興趣加入本團隊請與老師詳談。


Research

Molecular Mechanisms of Adaptive Evolution, Sequence Space and Fitness Landscape

Lab Introduction

The language of life consists of four alphabets: A, T, G, C. Through combination and permutation, these four basic elements create a diverse array of gene families, which together build up the blueprints of life forms ranging from viruses to humans. The possibility of this language (a.k.a. sequence space) is infinite: a 10-bp DNA sequence has ~1,000,000 (4^10) variants; the number of variants of a 20-aa protein sequence, ~100,000,000,000,000,000,000,000,000 (20^20), even exceeds the number of planets in the universe (~10^24)!

How many biological functions are harbored in the sequence space? Does there exist functionally similar variants with distinct sequence compositions? Why do some sequence variants carry just one function while others are multi-functional (promiscuity)? Could we invent artificial sequences with novel and useful properties?

Using microbes and their genes as the research materials, we apply genetic engineering, high-throughput screening/sequencing, and experimental evolution to explore the physiological basis of adaptive mutations, the evolutionary process of metabolic systems, genetic factors controlling the efficiency of gene expression, the biochemical basis of protein promiscuity, and the molecular mechanisms of species-species interaction underlying coevolution.

Recruitment Target Those who share passion for evolution or synthetic biology and can endure lab work (wet or dry) for whole days without getting bored. On-going projects are particularly adequate for those interested in biology but coming from engineering, physics, chemistry, or informatics backgrounds.


代表著作

Publications

  1. Chou HH, Marx CJ, Sauer U (2015) Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production. PLoS Genet. 11(2): e1005007.
  2. Chou HH, Delaney NF, Draghi JA, Marx CJ (2014) Mapping the fitness landscape of gene expression uncovers the cause of antagonism and sign epistasis between adaptive mutations. PLoS Genet. 10(2): e1004149.
  3. Chou HH, Marx CJ (2012) Optimization of gene expression through divergent mutational paths. Cell Reports 1:133-140.
  4. Chou HH, Chiu HC, Delaney NF, Segre D, Marx CJ (2011) Diminishing returns epistasis among beneficial mutations decelerates adaptation. Science 332:1190-1192.
  5. Chou HH, Berthet J, Marx CJ (2009) Fast growth increases the selective advantage of a mutation arising recurrently during evolution under metal limitation. PLoS Genet. 5(9): e1000652.