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In the 15 years since the discovery of hepatitis C virus (HCV), much has been learned about its role as a major causative agent of human liver disease and its ability to persist in the face of host-cell defences and the immune system. This review describes what is known about the diversity of HCV, the current classification of HCV genotypes within the family Flaviviridae and how this genetic diversity contributes to its pathogenesis. On one hand, diversification of HCV has been constrained by its intimate adaptation to its host. Despite the >30 % nucleotide sequence divergence between genotypes, HCV variants nevertheless remain remarkably similar in their transmission dynamics, persistence and disease development. Nowhere is this more evident than in the evolutionary conservation of numerous evasion methods to counteract the cell's innate antiviral defence pathways; this series of highly complex virus-host interactions may represent key components in establishing its 'ecological niche' in the human liver. On the other hand, the mutability and large population size of HCV enables it to respond very rapidly to new selection pressures, manifested by immune-driven changes in T- and B-cell epitopes that are encountered on transmission between individuals with different antigen-recognition repertoires. If human immunodeficiency virus type 1 is a precedent, future therapies that target virus protease or polymerase enzymes may also select very rapidly for antiviral-resistant mutants. These contrasting aspects of conservatism and adaptability provide a fascinating paradigm in which to explore the complex selection pressures that underlie the evolution of HCV and other persistent viruses.

Citation information in Europe Pubmed Central

Human endogenous retroviruses (HERVs) are the remnants of ancient germ cell infection by exogenous retroviruses and occupy up to 8% of the human genome. It has been suggested that HERV sequences have contributed to primate evolution by regulating the expression of cellular genes and mediating chromosome rearrangements. After integration approximately 28 million years ago, members of the HERV-K (HML-2) family have continued to amplify and recombine. To investigate the utility of HML-2 polymorphisms as markers for the study of more recent human evolution, we compiled a list of the structure and integration sites of sequences that are unique to humans and screened each insertion for polymorphism within the human genome databases. Of the total of 74 HML-2 sequences, 18 corresponded to complete or near-complete proviruses, 49 were solitary long terminal repeats (LTRs), 6 were incomplete LTRs, and 1 was a SVA retrotransposon. A number of different allelic configurations were identified including the alternation of a provirus and solitary LTR. We developed polymerase chain reaction-based assays for seven HML-2 loci and screened 109 human DNA samples from Africa, Europe, Asia, and Southeast Asia. Our results indicate that the diversity of HML-2 elements is higher in African than non-African populations, with population differentiation values ranging from 0.6 to 9.8%. These findings denote a recent expansion from Africa. We compare the phylogenetic relationships of HML-2 sequences that are unique to humans and consider whether these elements have played a role in the remodeling of the hominid genome.

Item #: 9377

Zones: 5a to 9b

Dormancy: Winter

Height: 24" tall

Culture: Sun to Part Sun

Origin: United States

Pot Size: 3.5" pot (24 fl. oz/0.7 L)

Item #: 8349

Zones: 5a to 9b

Dormancy: Winter

Height: 24" tall

Culture: Sun to Part Sun

Origin: United States Hybrid

Pot Size: 3.5" pot (24 fl. oz/0.7 L)

Item #: 11736

Zones: 5b to 9b, at least

Dormancy: Winter

Height: 16" tall

Culture: Sun to Part Sun

Origin: United States Hybrid

Pot Size: 3.5" pot (24 fl. oz/0.7 L)

Item #: 6268

Zones: 4a to 9b

Dormancy: Winter

Height: 8" tall

Culture: Sun to Part Sun

Origin: United States Hybrid

Pot Size: 3.5" pot (24 fl. oz/0.7 L)

Item #: 5246

Zones: 5a to 9b

Dormancy: Winter

Height: 24" tall

Culture: Sun to Part Sun

Origin: United States Hybrid

Pot Size: 3.5" pot (24 fl. oz/0.7 L)

Item #: 3060

Zones: 5a to 9b

Dormancy: Winter

Height: 12" tall

Culture: Sun to Part Sun

Origin: United States Hybrid

Pot Size: 3.5" pot (24 fl. oz/0.7 L)

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