Genomics of Ancient Pathogens: First Advances and Prospects

Abstract

Paleogenomics is one of the urgent and promising areas of interdisciplinary research in the today's world science. New genomic methods of ancient DNA (aDNA) analysis, such as next generation sequencing (NGS) technologies, make it possible not only to obtain detailed genetic information about historical and prehistoric human populations, but also to study individual microbial and viral pathogens and microbiomes from different ancient and historical objects. Studies of aDNA of pathogens by reconstructing their genomes have so far yielded complete sequences of the ancient pathogens that played significant role in the history of the world: Yersinia pestis (plague), Variola virus (smallpox), Vibrio cholerae (cholera), HBV (hepatitis B virus), as well as the equally important endemic human infectious agents: Mycobacterium tuberculosis (tuberculosis), Mycobacterium leprae (leprosy), and Treponema pallidum (syphilis). Genomic data from these pathogens complemented the information previously obtained by paleopathologists and allowed not only to identify pathogens from the past pandemics, but also to recognize the pathogen lineages that are now extinct, to refine chronology of the pathogen appearance in human populations, and to reconstruct evolutionary history of the pathogens that are still relevant to public health today. In this review, we describe state-of-the-art genomic research of the origins and evolution of many ancient pathogens and viruses and examine mechanisms of the emergence and spread of the ancient infections in the mankind history.

Keywords: ancient DNA; cholera; human populations; leprosy; paleogenomics; paleopathology; pathogen; plague; smallpox; syphilis; tuberculosis.

Fig. 1.

Schematic representation of the smallpox virus genome structure. Abbreviations: PTR, palindrome terminal region; CCT, concatemer; TR, tandem repeats; US, unique sequence (repeat-free). The structures of genomes of the cowpox virus (CPXV) [104], the ancient smallpox virus (aVARV) from archaeological remains found in Northern Europe and dating back to the Viking Age (600-1050 AD) [105], modern variola virus (VARV) [103], smallpox vaccinia virus (VACV) are shown. The diagram displays the auxiliary viral genes that distinguish the presented genomes. The genes are sorted from left to right into categories depending on function (color-coded), and then by their position in the genome, relative to each other. Yellow, lilac, and red colors indicate genes that are present and functioning (presumably functioning, in the case of aVARV); grey color indicates genes that are absent or inactivated (in the case of aVARV, these are absent or presumably inactive genes); the partially colored genes indicate that they are functioning/inactivated in some aVARV/VARV/VACV; white color indicates genes for which there is no information in the case of aVARV [105, 106].

Fig. 2.

Schematic model of the smallpox vaccine virus VACV evolution compiled on the basis of the genomes of modern smallpox vaccine VACV strains and historical smallpox vaccine strains obtained from various sources. Evolution processes are shown, which facilitated diversity of the strains of smallpox vaccine VACV viruses. The modern vaccine strains are shown in red color, the historic vaccine strains are shown in gray; aVACV presents the pool from different historic precursors of all present-day smallpox vaccine strains; HPXV is the horse smallpox virus, which is a hypothetic precursor of the historic vaccine virus; CPXV is the cowpox virus, which is a hypothetical precursor of the historical smallpox vaccine virus; the dotted line shows one of the probable evolutionary processes of the origin of horse smallpox virus HPXV from the CPXV virus.