Biomedical subjects

Robert Belshaw

Publications and source records attributed to Robert Belshaw.

7 recordsLinked to original sources

PubMed2005

High copy number in human endogenous retrovirus families is associated with copying mechanisms in addition to reinfection.

There are at least 31 families of human endogenous retroviruses (HERVs), each derived from an independent infection by an exogenous virus. Using evidence of purifying selection on HERV genes, we have shown previously that reinfection by replication-competent elements was the predominant mechanism of copying in some families. Here we analyze the evolution of 17 HERV families using d(N)/d(S) ratios and find a positive relationship between copy number and the use of additional copying mechanisms. All families with more than 200 elements have also used one or more of the following mechanisms: (1) complementation in trans (elements copied by other elements of the same family; HERV-H and ERV-9), (2) retrotransposition in cis (elements copying themselves) within germ-line cells (HERV-K(HML3)), and (3) being copied by non-HERV machinery (HERV-W). We discuss why these other mechanisms are rare in most families and suggest why complementation in trans is significant only in the larger families.

Endogenous Retroviruses↗

PubMed2005

Genomewide screening reveals high levels of insertional polymorphism in the human endogenous retrovirus family HERV-K(HML2): implications for present-day activity.

The published human genome sequence contains many thousands of endogenous retroviruses (HERVs) but all are defective, containing nonsense mutations or major deletions. Only the HERV-K(HML2) family has been active since the divergence of humans and chimpanzees; it contains many members that are human specific, as well as several that are insertionally polymorphic (an inserted element present only in some human individuals). Here we perform a genomewide survey of insertional polymorphism levels in this family by using the published human genome sequence and a diverse sample of 19 humans. We find that there are 113 human-specific HERV-K(HML2) elements in the human genome sequence, 8 of which are insertionally polymorphic (11 if we extrapolate to those within regions of the genome that were not suitable for amplification). The average rate of accumulation since the divergence with chimpanzees is thus approximately 3.8 x 10(-4) per haploid genome per generation. Furthermore, we find that the number of polymorphic elements is not significantly different from that predicted by a standard population genetic model that assumes constant activity of the family until the present. This suggests to us that the HERV-K(HML2) family may be active in present-day humans. Active (replication-competent) elements are likely to have inserted very recently and to be present at low allele frequencies, and they may be causing disease in the individuals carrying them. This view of the family from a population perspective rather than a genome perspective will inform the current debate about a possible role of HERV-K(HML2) in human disease.

DNA, Viral↗

PubMed2004

BlastAlign: a program that uses blast to align problematic nucleotide sequences.

UNLABELLED: BlastAlign uses NCBI blastn to build a multiple nucleotide alignment and is intended for use with sequences that have large indels or are otherwise difficult to align globally. The program builds a matrix representing regions of homology along the sequences, from which it selects the 'most representative' sequence and then extracts the blastn query-anchored multiple alignment for this sequence. The matrix is printed and allows subgroups to be identified visually and an option allows other sequences to be used as the 'most representative'. The program contains elements of both Perl and Python and will run on UNIX (including Mac OSX) and DOS. An additional Perl program BlastAlignP uses tblastn to align nucleotide sequences to a single amino acid sequence, thus allowing an open reading frame to be maintained in the resulting multiple alignment. AVAILABILITY: It is freely available at http://www.bio.ic.ac.uk/research/belshaw/BlastAlign.tar and at http://evolve.zoo.ox.ac.uk/software/blastalign.

Algorithms↗

PubMed2004

Long-term reinfection of the human genome by endogenous retroviruses.

Endogenous retrovirus (ERV) families are derived from their exogenous counterparts by means of a process of germ-line infection and proliferation within the host genome. Several families in the human and mouse genomes now consist of many hundreds of elements and, although several candidates have been proposed, the mechanism behind this proliferation has remained uncertain. To investigate this mechanism, we reconstructed the ratio of nonsynonymous to synonymous changes and the acquisition of stop codons during the evolution of the human ERV family HERV-K(HML2). We show that all genes, including the env gene, which is necessary only for movement between cells, have been under continuous purifying selection. This finding strongly suggests that the proliferation of this family has been almost entirely due to germ-line reinfection, rather than retrotransposition in cis or complementation in trans, and that an infectious pool of endogenous retroviruses has persisted within the primate lineage throughout the past 30 million years. Because many elements within this pool would have been unfixed, it is possible that the HERV-K(HML2) family still contains infectious elements at present, despite their apparent absence in the human genome sequence. Analysis of the env gene of eight other HERV families indicated that reinfection is likely to be the most common mechanism by which endogenous retroviruses proliferate in their hosts.

Endogenous Retroviruses↗

PubMed2003

The cytogenetics of thelytoky in a predominantly asexual parasitoid wasp with covert sex.

Asexual lineages in the parasitoid wasp Lysiphlebus fabarum (Hymenoptera: Braconidae: Aphidiinae) have previously been shown to have occasionally undergone sexual reproduction and recombination with males from related sexual populations. In the present study, the cytogenetic system of asexual females in this species is shown by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining to be central fusion automixis. This system has the potential to allow occasional sex and recombination without leading to an elevation of ploidy and with the maintenance of at least some heterozygosity. No evidence of the bacterial symbiont Wolbachia was found, and the observed system was compared with that in parasitoid wasps where asexuality is the result of Wolbachia infection.

Animals↗

PubMed2002

Simultaneous molecular and morphological analysis of braconid relationships (Insecta: Hymenoptera: Braconidae) indicates independent mt-tRNA gene inversions within a single wasp family.

We investigated the phylogeny of the Braconidae (Insecta: Hymenoptera) with a much expanded data set compared with that of previous attempts, employing 16S and 28S rDNA gene fragments, together with a suite of morphological characters, from 74 ingroup taxa. Most notably, parsimony analyses under a range of models recovered the Aphidiinae as sister group to the cyclostomes and the Ichneutinae as sister group to the microgastroids. The cyclostomes were recovered as a natural group only if certain, putatively misplaced genera (Mesostoa, Aspilodemon) were excluded from them. Further, mapping of rearrangement characters onto this phylogeny of the Braconidae indicated parallel inversions of the mt-tRNAD gene, with the two instances of inversion distinguishable by the presence or absence of an additional tRNA gene (tRNAH). This is the first report of a parallel inversion of a mt-tRNA gene and makes the Braconidae the first metazoan family to display both parallel inversions and translocations.

Animals↗

PubMed2002

Robustness of ancestral state estimates: evolution of life history strategy in ichneumonoid parasitoids.

We test hypotheses for the evolution of a life history trait among a group of parasitoid wasps (Hymenoptera: Ichneumonoidea), namely, the transition among koinobiont parasitoids (parasitoids whose hosts continue development after oviposition) between attacking exposed hosts and attacking hosts that are concealed within plant tissue. Using a range of phylogeny estimates based on 28S rDNA sequences, we use maximum parsimony (MP) and maximum likelihood (ML) methods to estimate the ancestral life history traits for the main clades in which both traits occur (using the programs MacClade and Discrete, respectively). We also assess the robustness of these estimates; for MP, we use step matrices in PAUP* to find the minimum weight necessary to reverse estimates or make them ambiguous, and for ML, we measure the differences in likelihood after fixing the ancestral nodes at the alternative states. We also measure the robustness of the MP ancestral state estimate against uncertainties in the phylogeny estimate, manipulating the most-parsimonious tree in MacClade to find the shortest suboptimal tree in which the ancestral state estimate is reversed or made ambiguous. Using these methods, we find strong evidence supporting two transitions among koinobiont Ichneumonoidea: (1) to attacking exposed hosts in a clade consisting of the Helconinae and related subfamilies, and (2) the reverse transition in a clade consisting of the Euphorinae and related subfamilies. In exploring different methods of analyzing variable-length DNA sequences, we found that direct optimization with POY gave some clearly erroneous results that had a profound effect on the overall phylogeny estimate. We also discuss relationships within the superfamily and expand the Mesostoinae to include all the gall-associated braconids that form the sister group of the Aphidiinae.

Animals↗