Am Velasco

Low complexity regions (LCRs) contribute to the hypervariability of the HIV-1 gp120 protein

Low complexity regions (LCRs) are sequences of nucleic acids or proteins defined by a compositional bias. Their occurrence has been confirmed in sequences of the three cellular lineages (Bacteria, Archaea and Eucarya), and has also been reported in viral genomes. We present here the results of a detailed computer analysis of the LCRs present in the HIV-1 glycoprotein 120 (gp120) encoded by the viral gene env. The analysis was performed using a sample of 3637 Env polyprotein sequences derived from 4117 completely sequenced and translated HIV-1 genomes available in public databases as of December 2012. We have identified 1229 LCRs located in four different regions of the gp120 protein that correspond to four of the five regions that have been identified as hypervariable (V1, V2, V4 and V5). The remaining 29 LCRs are found in the signal peptide and in the conserved regions C2, C3, C4 and C5. No LCR has been identified in the hypervariable region V3. The LCRs detected in the V1, V2, V4, and V5 hypervariable regions exhibit a high Asn content in their amino acid composition, which very likely correspond to glycosylation sites, which may contribute to the retroviral ability to avoid the immune system. In sharp contrast with what is observed in gp120 proteins lacking LCRs, the glycosylation sites present in LCRs tend to be clustered towards the center of the region forming well-defined islands. The results presented here suggest that LCRs represent a hitherto undescribed source of genomic variability in lentivirus, and that these repeats may represent an important source of antigenic variation in HIV-1 populations. The results reported here may exemplify the evolutionary processes that may have increased the size of primitive cellular RNA genomes and the role of LCRs as a source of raw material during the processes of evolutionary acquisition of new functions.

Molecular Biology and the Reconstruction of Microbial Phylogenies: Des Liaisons Dangereuses?

Only half-a-century after the DNA double chain model was first suggested, molecular biology has become one of the most provocative, rapidly developing fields of of scientific research, that has led not only to tantalizing new findings on processes and mechanisms at the molecular level, but also to major conceptual revolutions in life sciences. Is there any hope of developing methodological approaches and theoretical frameworks not only to make sense of the overwhelming growing body of data that this relatively new field is producing, but also to use them to develop a more integrative, truly multidisciplinaiy understanding of biological phenomena? As Peter Bowler wrote a few years ago, Charles Darwin and his followers were accutely aware that “evolutionism’s strength as a theory came fom its ability to make sense out of a vast range of otherwise meaningless facts” (Bowler, 1990). This situation has not changed. Evolutionary biology may be in a state of major turmoil, but its unifying powers have not diminished at all. In fact, they probably represent one of the most promising possibilities of overcoming the perils of reductionism that have plagued molecular biology since its inception.

The Pope, condoms, and the evolution of HIV

This reflection focuses on HIV resistance to antiretroviral therapy and the importance of using condoms. It touches on the Pope’s statements on the use of condoms and their inefficiency to prevent HIV transmission and argues against it stating that condoms play a key role in limiting the HIV pandemic.

Prebiotic organic synthesis and the emergence of life: from the Miller experiment to the start of biological evolution

Laboratory experiments have shown how easy it is to produce a number of biochemical monomers under reducing conditions. Such empirical support began to accumulate in 1953, when Stanley L. Miller, then a graduate student working with Harold C. Urey at the University of Chicago, achieved the first successful synthesis of organic compounds under plausible primordial conditions The action of electric discharges acting for a week over a mixture of CH4, NH3, H2, and H2O; racemic mixtures of several proteinic amino acids were produced, as well as hydroxy acids, urea, and other organic molecules (Miller 1953). The easiness of formation in one-pot reactions of amino acids, purines, and pyrimidines strongly suggest these molecules and many others were components of the prebiotic broth (cf. Miller and Lazcano, 2002).