【2011新英格兰】Microbial Genomics and Infectious Diseases

蓝鱼o_0

N Engl J Med 2011;365:347-57.

The pace of technical advancement in microbial genomics has been breathtaking. Since 1995, when the first complete genome sequence of a free-living organism, Haemophilus influenzae, was published,1 1554 complete bacterial genome sequences (the majority of which are from pathogens) and 112 complete archaeal genome sequences have been determined, and more than 4800 and 90, respectively, are in progress.2 A total of 41 complete eukaryotic genome sequences
have been determined (19 from fungi), and more than 1100 are in progress. Complete reference genome sequences are available for 2675 viral species, and for some of these species, a large number of strains have been completely sequenced. Nearly
40,000 strains of influenza virus3 and more than 300,000 strains of human immunodeficiency virus (HIV) type 1 have been partially sequenced.4 However, the selection of microbes and viruses for genome sequencing is heavily biased toward the tiny minority that are amenable to cultivation in the laboratory, numerically dominant in particular habitats of interest (e.g., the human body), and associated with disease. In 2006, investigators reported in-depth metagenomic sequence data from a human
mixed microbial community5; in 2007 more than 1000 genes from single cells of cultivation-resistant bacteria were identified.6 Since then, a flood of such data has ensued (Fig. 1).7-9 Individual investigators can now produce a draft sequence of a
bacterial genome containing 4 million base pairs in about a day.10-12 The revolution in DNA-sequencing technology has to a large extent democratized microbial genomics and altered the way infectious diseases are studied.11 However, gene annotation
and error correction still take time and effort. Today, the major challenges in microbial genomics are to predict the function of gene products and the behavior of organisms and communities from their sequences and to use genomic data to develop
improved tools for managing infectious diseases.