Genomic Variation and Evolution of HERV-H and other Endogenous Retroviruses (ERVs)

• An exogenous retrovirus (XRV) that integrates into a germ cell may be inherited as a Mendelian gene; it becomes an endogenous retrovirus (ERV). The human genome consists of up to 8% HERVs. The gammaretroviral (ERV class I) HERV-H, with 926 members, is the largest ERV group. Despite millions of years since integration, it has polymorphic envelope open reading frames in at least three loci. Selections for functional envelopes are indicated on chromosomes 1 and 2. However, envelopes were present only in a fraction of the total HERV-H. Mutated polymerases, indicating old ERVs, contradicted relatively intact long terminal repeats. To explain this, we formulated a “Midwife” element theory where proteins are complemented in trans. A phylogenetic analysis did not support separate HERV-H and -F groups. The new taxonomy included HERV-H like (RGH2-like and RTVLH2-like subgroups) and Adjacent HERV-H like. A bioinformatic reconstruction of a putative ancestral HERV-H exposed novel traits. Two nucleocapsid zinc fingers and a pronounced nucleotide bias for C in the HERV-H like were unique among the gammaretroviruses. Two recently integrated gammaretroviral groups (PtNeo-I[PTERV1] and -II) were found in chimpanzees but not in humans. The PtNeo groups were most similar to baboon ERVs and a macaque sequence, but neither to other chimpanzee nor to any human gammaretroviruses. The pattern was consistent with cross-species transfer via predation. To advance the retroviral taxonomy, we projected structural markers over sequence phylogenetic trees. A number of markers were useful to distinguish between genera and to delineate groups. Basic retroviral knowledge is vital to understand emerging infections. Phylogenetic analyses of taxonomically improved sequences, facilitates the search for common retroviral denominators to target. This thesis provided new insights in retroviral evolution and taxonomy using the ERVs, with special focus on the large gammaretroviral HERV-H group, as an additional source of information next to that of XRVs.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Microbiology

Endogenous Retrovirus (ERV)

HERV-H

Phylogeny

Evolution

Sequence Variation

Polymorphism

Recent Integrations

Horizontal Transfer

Master Elements

Taxonomy

Mikrobiologi

Microbiology, immunology, infectious diseases

Mikrobiologi, immunologi, infektionssjukdomar

Publikations- och innehållstyp

vet (ämneskategori)

dok (ämneskategori)