Biology subjects

Philipp Khaitovich

Publications and source records attributed to Philipp Khaitovich.

3 recordsLinked to original sources

bioRxiv2015

A Chronological Atlas of Natural Selection in the Human Genome during the Past Half-million Years

The spatiotemporal distribution of recent human adaptation is a long standing question. We developed a new coalescent-based method that collectively assigned human genome regions to modes of neutrality or to positive, negative, or balancing selection. Most importantly, the selection times were estimated for all positive selection signals, which ranged over the last half million years, penetrating the emergence of anatomically modern human (AMH). These selection time estimates were further supported by analyses of the genome sequences from three ancient AMHs and the Neanderthals. A series of brain function-related genes were found to carry signals of ancient selective sweeps, which may have defined the evolution of cognitive abilities either before Neanderthal divergence or during the emergence of AMH. Particularly, signals of brain evolution in AMH are strongly related to Alzheimers disease pathways. In conclusion, this study reports a chronological atlas of natural selection in Human.

Evolutionary Biology↗

bioRxiv2014

Evaluating intra- and inter-individual variation in the human placental transcriptome

BackgroundGene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta.\n\nResultsWe estimate that on average, 33.2%, 58.9% and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling and metabolism. Many biological traits demonstrated correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome (65% of expressed genes) exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection (26%), directional selection (4.9%), or diversifying selection (4.8%).\n\nConclusionWe apportion placental gene expression variation into individual, population and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.

Genomics↗

bioRxiv2014

Heterochrony explains convergent testis evolution in primates

In independent mammalian lineages where females mate with multiple males (multi-male mating strategies), males have evolved larger testicles relative to those lineages where females mate with fewer males (single-male mating strategies). Here we study published bulk testis transcriptomes from humans, chimpanzees, gorillas and rhesus macaques, as well as mice and rats. Employing a formal model of adaptive evolution, we find that testis transcriptomes have also evolved convergently, reflecting each species mating strategy. Using deconvolution, we infer that testis transcriptome divergence patterns largely reflect convergent shifts in tissue cell type composition. However, we also identify modest amounts of convergent evolution at the cell-autonomous level by analyzing cell-type specific transcriptome data from spermatids and spermatocytes. We further show that in the single-male mating primates, human and gorilla, testis transcriptome profiles are paedomorphic relative to those of multi-male primates, chimpanzee and macaque, suggesting that shifts in timing or rate of testis development could underlie convergent changes in testis mass, histology, and transcriptomes.

Evolutionary Biology↗