학술논문

Whole-genome sequences from wild-type and laboratory-evolved strains define the alleleome and establish its hallmarks
Document Type
article
Source
Proceedings of the National Academy of Sciences of the United States of America. 120(15)
Subject
Genetics
Human Genome
Biotechnology
Genetic Variation
Mutation
Escherichia coli
Genome
Bacterial
Amino Acid Sequence
alignment
allele
laboratory evolution
mutation
sequence
Language
Abstract
The genomic diversity across strains of a species forms the genetic basis for differences in their behavior. A large-scale assessment of sequence variation has been made possible by the growing availability of strain-specific whole-genome sequences (WGS) and with the advent of large-scale databases of laboratory-acquired mutations. We define the Escherichia coli "alleleome" through a genome-scale assessment of amino acid (AA) sequence diversity in open reading frames across 2,661 WGS from wild-type strains. We observe a highly conserved alleleome enriched in mutations unlikely to affect protein function. In contrast, 33,000 mutations acquired in laboratory evolution experiments result in more severe AA substitutions that are rarely achieved by natural selection. Large-scale assessment of the alleleome establishes a method for the quantification of bacterial allelic diversity, reveals opportunities for synthetic biology to explore novel sequence space, and offers insights into the constraints governing evolution.