The laboratory of Liran Carmel

• [Freethought Blogs ] [2023] A complete story with a satisfying conclusion
• [Al Jazeera English] [2022] Who were the Denisovans? News Al Jazeera

• LINADMIX: evaluating the effect of ancient admixture events on modern populations.
  Bioinformatics (Oxford, England) [2023] Abstract
  Lily Agranat-Tamir, Shamam Waldman, Naomi Rosen, Benjamin Yakir, Shai Carmi, Liran Carmel

LINADMIX: evaluating the effect of ancient admixture events on modern populations.

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The rise in the number of genotyped ancient individuals provides an opportunity to estimate population admixture models for many populations. However, in models describing modern populations as mixtures of ancient ones, it is typically difficult to estimate the model mixing coefficients and to evaluate its fit to the data.
• Alu exaptation enriches the human transcriptome by introducing new gene ends.
  RNA biology [2022] Abstract Free full text
  Eitan Lavi, Liran Carmel

Alu exaptation enriches the human transcriptome by introducing new gene ends.

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In mammals, transposable elements are largely silenced, but under fortuitous circumstances may be co-opted to play a functional role. Here, we show that when Alu elements are inserted within or nearby genes in sense orientation, they may contribute to the transcriptome diversity by forming new cleavage and polyadenylation sites. We mapped these new gene ends in human onto the Alu sequence and identified three hotspots of cleavage and polyadenylation site formation. Interestingly, the native Alu sequence does not contain any canonical polyadenylation signal. We therefore studied what evolutionary processes might explain the formation of these specific hotspots of novel gene ends. We show that two of the three hotspots might have emerged from mutational processes that turned sequences that resemble polyadenylation signals into full-blown canonical signals, whereas one hotspot is tightly linked to the process of Alu insertion into the genome. Overall, Alu elements may lie behind the formation of 302 new gene end variants, affecting a total of 243 genes. Intergenic Alu elements may elongate genes by creating a downstream cleavage site, intronic Alu elements may lead to gene variants which code for truncated proteins, and 3UTR Alu elements may result in gene variants with alternative 3UTR.
• Lead in Archeological Human Bones Reflecting Historical Changes in Lead Production.
  Environmental science technology [2021] Abstract
  Yigal Erel, Ron Pinhasi, Alfredo Coppa, Adi Ticher, Ofir Tirosh, Liran Carmel

Lead in Archeological Human Bones Reflecting Historical Changes in Lead Production.

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Forty years ago, in a seminal paper published in Science, Settle and Patterson used archeological and historical data to estimate the rates of worldwide lead production since the discovery of cupellation, approximately 5000 years ago. Here, we record actual lead exposure of a human population by direct measurements of the concentrations of lead in petrous bones of individuals representing approximately 12?000 years of inhabitation in Italy. This documentation of lead pollution throughout human history indicates that, remarkably, much of the estimated dynamics in lead production is replicated in human exposure. Thus, lead pollution in humans has closely followed anthropogenic lead production. This observation raises concerns that the forecasted increase in the production of lead and other metals might affect human health in the near future.
• Differential DNA methylation of vocal and facial anatomy genes in modern humans.
  Nature communications [2021] Abstract Free full text
  David Gokhman, Malka Nissim-Rafinia, Lily Agranat-Tamir, Genevieve Housman, Raquel Garca-Prez, Esther Lizano, Olivia Cheronet, Swapan Mallick, Maria A Nieves-Coln, Heng Li, Songl Alpaslan-Roodenberg, Mario Novak, Hongcang Gu, Jason M Osinski, Manuel Ferrando-Bernal, Pere Gelabert, Iddi Lipende, Deus Mjungu, Ivanela Kondova, Ronald Bontrop, Ottmar Kullmer, Gerhard Weber, Tal Shahar, Mona Dvir-Ginzberg, Marina Faerman, Ellen E Quillen, Alexander Meissner, Yonatan Lahav, Leonid Kandel, Meir Liebergall, Mara E Prada, Julio M Vidal, Richard M Gronostajski, Anne C Stone, Benjamin Yakir, Carles Lalueza-Fox, Ron Pinhasi, David Reich, Tomas Marques-Bonet, Eran Meshorer, Liran Carmel

Differential DNA methylation of vocal and facial anatomy genes in modern humans.

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Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and experimentally measured DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that likely emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes associated with face and vocal tract anatomy went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-associated genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract.
• Harnessing epigenetics to study human evolution.
  Current opinion in genetics development [2021] Abstract
  Yoav Mathov, Daniel Batyrev, Eran Meshorer, Liran Carmel

Harnessing epigenetics to study human evolution.

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Recent advances in ancient DNA extraction and high-throughput sequencing technologies enabled the high-quality sequencing of archaic genomes, including the Neanderthal and the Denisovan. While comparisons with modern humans revealed both archaic-specific and human-specific sequence changes, in the absence of gene expression information, understanding the functional implications of such genetic variations remains a major challenge. To study gene regulation in archaic humans, epigenetic research comes to our aid. DNA methylation, which is highly correlated with transcription, can be directly measured in modern samples, as well as reconstructed in ancient samples. This puts DNA methylation as a natural basis for comparative epigenetics between modern humans, archaic humans and nonhuman primates.
• Reconstructing Denisovan Anatomy Using DNA Methylation Maps.
  Cell [2020] Abstract
  David Gokhman, Nadav Mishol, Marc de Manuel, David de Juan, Jonathan Shuqrun, Eran Meshorer, Tomas Marques-Bonet, Yoel Rak, Liran Carmel

Reconstructing Denisovan Anatomy Using DNA Methylation Maps.

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Denisovans are an extinct group of humans whose morphology remains unknown. Here, we present a method for reconstructing skeletal morphology using DNA methylation patterns. Our method is based on linking unidirectional methylation changes to loss-of-function phenotypes. We tested performance by reconstructing Neanderthal and chimpanzee skeletal morphologies and obtained 85 precision in identifying divergent traits. We then applied this method to the Denisovan and offer a putative morphological profile. We suggest that Denisovans likely shared with Neanderthals traits such as an elongated face and a wide pelvis. We also identify Denisovan-derived changes, such as an increased dental arch and lateral cranial expansion. Our predictions match the only morphologically informative Denisovan bone to date, as well as the Xuchang skull, which was suggested by some to be a Denisovan. We conclude that DNA methylation can be used to reconstruct anatomical features, including some that do not survive in the fossil record.
• Nucleotide composition affects codon usage toward the 3-end.
  PloS one [2020] Abstract Free full text
  Fouad Zahdeh, Liran Carmel

Nucleotide composition affects codon usage toward the 3-end.

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The 3-end of the coding sequence in several species is known to show specific codon usage bias. Several factors have been suggested to underlie this phenomenon, including selection against translation efficiency, selection for translation accuracy, and selection against RNA folding. All are supported by some evidence, but there is no general agreement as to which factors are the main determinants. Nor is it known how universal this phenomenon is, and whether the same factors explain it in different species. To answer these questions, we developed a measure that quantifies the codon usage bias at the gene end, and used it to compute this bias for 91 species that span the three domains of life. In addition, we characterized the codons in each species by features that allow discrimination between the different factors. Combining all these data, we were able to show that there is a universal trend to favor AT-rich codons toward the gene end. Moreover, we suggest that this trend is explained by avoidance from forming RNA secondary structures around the stop codon, which may interfere with normal translation termination.