Tanmoy Bhattacharya

Globally, human immunodeficiency virus-type 1 (HIV-1) is extraordinarily variable, and this diversity poses a major obstacle to AIDS vaccine development. Currently, candidate vaccines are derived from isolates, with the hope that they will be sufficiently cross-reactive to protect against circulating viruses. This may be overly optimistic, however, given that HIV-1 envelope proteins can differ in more than 30% of their

Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4(+) T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12-20 mo, viruses exhibited concentrated mutations at 17-34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses.

Background: Concerted evolution is normally used to describe parallel changes at different sites in a genome, but it is also observed in languages where a specific phoneme changes to the same other phoneme in many words in the lexicon—a phenomenon known as regular sound change. We develop a general statistical model that can detect concerted changes in aligned sequence data and apply it to study regular sound changes in the Turkic language family. Results: Linguistic evolution, unlike the genetic substitutional process, is dominated by events of concerted evolutionary change. Our model identified more than 70 historical events of regular sound change that occurred throughout the evolution of the Turkic language family, while simultaneously inferring a dated phylogenetic tree. Including regular sound changes yielded an approximately 4-fold improvement in the characterization of linguistic change over a simpler model of sporadic change, improved phylogenetic inference, and returned more reliable and plausible dates for events on the phylogenies. The historical timings of the concerted changes closely follow a Poisson process model, and the sound transition networks derived from our model mirror linguistic expectations. Conclusions: We demonstrate that a model with no prior knowledge of complex concerted or regular changes can nevertheless infer the historical timings and genealogical placements of events of concerted change from the signals left in contemporary data. Our model can be applied wherever discrete elements—such as genes, words, cultural trends, technologies, or morphological traits—can change in parallel within an organism or other evolving group.

How universal is human conceptual structure? The way concepts are organized in the human brain may reflect distinct features of cultural, historical, and environmental background in addition to properties universal to human cognition. Semantics, or meaning expressed through language, provides indirect access to the underlying conceptual structure, but meaning is notoriously difficult to measure, let alone parameterize. Here, we provide an empirical measure of semantic proximity between concepts using cross-linguistic dictionaries to translate words to and from languages carefully selected to be representative of worldwide diversity. These translations reveal cases where a particular language uses a single " polysemous " word to express multiple concepts that another language represents using distinct words. We use the frequency of such polysemies linking two concepts as a measure of their semantic proximity and represent the pattern of these linkages by a weighted network. This network is highly structured: Certain concepts are far more prone to polysemy than others, and naturally interpretable clusters of closely related concepts emerge. Statistical analysis of the polysemies observed in a subset of the basic vocabulary shows that these structural properties are consistent across different language groups, and largely independent of geography, environment, and the presence or absence of a literary tradition. The methods developed here can be applied to any semantic domain to reveal the extent to which its conceptual structure is, similarly, a universal attribute of human cognition and language use. polysemy | human cognition | semantic universals | conceptual structure | network comparison T he space of concepts expressible in any language is vast. There has been much debate about whether semantic similarity of concepts (i.e., the layout of this space) is shared across languages (1–9). On the one hand, all human beings belong to a single species characterized by, among other things, a shared set of cognitive abilities. On the other hand, the 6,000 or so extant human languages spoken by different societies in different environments across the globe are extremely diverse (10–12). This diversity reflects accidents of history as well as adaptations to local environments. Notwithstanding the vast and multifarious forms of culture and language, most psychological experiments about semantic universality have been conducted on members of Western, educated, industrial, rich, democratic (WEIRD) societies, and it has been questioned whether the results of such research are valid across all types of societies (13). The fundamental problem of quantifying the degree to which conceptual structures expressed in language are due to universal properties of human cognition, as opposed to the particulars of cultural history or the environment inhabited by a society, remains unresolved. A resolution of this problem has been hampered by a major methodological difficulty. Linguistic meaning is an abstract construct that needs to be inferred indirectly from observations, and hence is extremely difficult to measure. This difficulty is even more apparent in the field of lexical semantics, which deals with how concepts are expressed by individual words. In this regard, meaning contrasts both with phonetics, in which instrumental measurement of physical properties of articulation and acoustics is relatively straightforward, and with grammatical structure, for which there is general agreement on a number of basic units of analysis (14). Much lexical semantic analysis relies on linguists' introspection, and the multifaceted dimensions of meaning currently lack a formal characterization. To address our primary question, it is necessary to develop an empirical method to characterize the space of concepts. We arrive at such a measure by noting that translations uncover the alternate ways that languages partition meanings into words. Many words are polysemous (i.e., they have more than one meaning); thus, they refer to multiple concepts to the extent that these meanings or senses can be individuated (15). Translations uncover instances of polysemy where two or more concepts are fundamentally different enough to receive distinct words in some languages, yet similar enough to share a common word in other languages. The frequency with which two concepts share a single polysemous word in a sample of unrelated languages provides a measure of semantic similarity between them. We chose an unbiased sample of 81 languages in a phylogeneti-cally and geographically stratified way, according to the methods of typology and universals research (12, 16–18) (SI Appendix, section I). Our large and diverse sample of languages allows us to avoid the pitfalls of research based solely on WEIRD societies. Using it, we can distinguish the empirical patterns we detect in the linguistic data as contributions arising from universal conceptual structure from those contributions arising from artifacts of the speakers' history or way of life. Significance Semantics, or meaning expressed through language, provides indirect access to an underlying level of conceptual structure. To what degree this conceptual structure is universal or is due to properties of cultural histories, or to the environment inhabited by a speech community, is still controversial. Meaning is notoriously difficult to measure, let alone parameterize, for quantitative comparative studies. Using cross-linguistic dictionaries across languages carefully selected as an unbiased sample reflecting the diversity of human languages, we provide an empirical measure of semantic relatedness between concepts. Our analysis uncovers a universal structure underlying the sampled vocabulary across language groups independent of their phylogenetic relations, their speakers' culture, and geographic environment.

ABSTRACT Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) evade containment by CD8+ T lymphocytes through focused epitope mutations. However, because of limitations in the numbers of viral sequences that can be sampled, traditional sequencing technologies have not provided a true representation of the plasticity of these viruses or the intensity of CD8+ T lymphocyte-mediated selection pressure.