Biology subjects

Venkataram, S.

Publications and source records attributed to Venkataram, S..

3 recordsLinked to original sources

bioRxiv2018

Stress response, behavior, and development are shaped by transposable element-induced mutations in Drosophila

Mapping genotype to phenotype is challenging because of the difficulties in identifying both the traits under selection and the specific genetic variants underlying these traits. Most of the current knowledge of the genetic basis of adaptive evolution is based on the analysis of single nucleotide polymorphisms (SNPs). Despite increasing evidence for their causal role, the contribution of structural variants to adaptive evolution remains largely unexplored. In this work, we analyzed the population frequencies of 1,615 Transposable Element (TE) insertions in 91 samples from 60 worldwide natural populations of Drosophila melanogaster. We identified a set of 300 TEs that are present at high population frequencies, and located in genomic regions with high recombination rate, where the efficiency of natural selection is high. The age and the length of these 300 TEs are consistent with relatively young and long insertions reaching high frequencies due to the action of positive selection. Indeed, we, and others, found evidence of selective sweeps and/or population differentiation for 65 of them. The analysis of the genes located nearby these 65 candidate adaptive insertions suggested that the functional response to selection is related with the GO categories of response to stimulus, behavior, and development. We further showed that a subset of the candidate adaptive TEs affect expression of nearby genes, and five of them have already been linked to an ecologically relevant phenotypic effect. Our results provide a more complete understanding of the genetic variation and the fitness-related traits relevant for adaptive evolution. Similar studies should help uncover the importance of TE-induced adaptive mutations in other species as well.

evolutionary biology↗

bioRxiv2017

High-Resolution Mapping Of cis-Regulatory Variation In Budding Yeast

Genetic variants affecting gene expression levels are a major source of phenotypic variation. The approximate locations of these variants can be mapped as expression quantitative trait loci (eQTLs); however a major limitation of eQTLs is their low resolution, which precludes investigation of the causal variants and their molecular mechanisms. Here we report RNA-seq and full genome sequences for 85 diverse isolates of the yeast Saccharomyces cerevisiae--including wild, domesticated, and human clinical strains--which allowed us to perform eQTL mapping with 50-fold higher resolution than previously possible. In addition to variants in promoters, we uncovered an important role for variants in 3 untranslated regions, especially those affecting binding of the PUF family of RNA-binding proteins. The eQTLs are predominantly under purifying selection, particularly those affecting essential genes and conserved genes. However, applying the sign test for lineage-specific selection revealed the polygenic up-regulation of dozens of biofilm suppressor genes in strains isolated from human patients, consistent with the key role of biofilms in fungal pathogenicity. In addition, a single variant in the promoter of a biofilm suppressor, NIT3, showed the strongest genome-wide association with clinical origin. Altogether our results demonstrate the power of high-resolution eQTL mapping in understanding the molecular mechanisms of regulatory variation, as well as the natural selection acting on this variation that drives adaptation to environments ranging from laboratories to vineyards to the human body.

genetics↗

bioRxiv2016

Pervasive adaptation in Plasmodium-interacting proteins in mammals

The protozoan genus Plasmodium causes malaria in dozens of mammal species, including humans, non-human primates, rodents, and bats. In humans, Plasmodium infections have caused hundreds of millions of documented deaths, imposing strong selection on certain populations and driving the emergence of several resistance alleles. Over the deep timescale of mammalian evolution, however, little is known about host adaptation to Plasmodium. In this work, we expand the collection of known Plasmodium-interacting-proteins (PIPs) in mammalian hosts from ~10 to 410, by manually curating thousands of scientific abstracts. We use comparative tests of adaptation to show that PIPs have experienced >3 times more positive selection than similar mammalian proteins, consistent with Plasmodium as a major and long-standing selective pressure. PIP adaptation is strongly linked to gene expression in the blood, liver, and lung, all of which are clinically relevant tissues in Plasmodium infection. Interestingly, we find that PIPs with immune functions are especially enriched for additional interactions with viruses or bacteria, which together drive a 3.7-fold excess of adaptation. These pleiotropic interactions with unrelated pathogens, along with pressure from other Plasmodium-like Apicomplexan parasites, may help explain the PIP adaptation we observe in all clades of the mammalian tree. As a case study, we also show that alpha-spectrin, the major membrane component of mammalian red blood cells, has experienced accelerated adaptation in domains known to interact specifically with Plasmodium proteins. Similar interactions with Plasmodium-like parasites appear to have driven substantial adaptation in hundreds of host proteins throughout mammalian evolution.

evolutionary biology↗