Biology subjects

Yakir, B.

Publications and source records attributed to Yakir, B..

3 recordsLinked to original sources

bioRxiv2024

RoAM: computational reconstruction of ancient methylomes and identification of differentially methylated regions

Identifying evolutionary changes in DNA methylation bears a huge potential for unraveling adaptations that have occurred in modern humans. Over the past decade, computational methods to reconstruct DNA methylation patterns from ancient DNA sequences have been developed, allowing for the exploration of DNA methylation changes during the past hundreds of thousands of years of human evolution. Here, we introduce a new version of RoAM (Reconstruction of Ancient Methylation), a flexible tool that allows for the reconstruction of ancient methylomes, as well as the identification of differentially methylated regions between ancient populations. RoAM incorporates a series of filtering and quality control steps, resulting in highly reliable DNA methylation maps that exhibit similar characteristics to modern maps. To showcase RoAMs capabilities, we used it to compare ancient methylation patterns between pre- and post-Neolithic revolution samples from the Balkans. Differentially methylated regions separating these populations are shown to be associated with genes related to regulation of sugar metabolism. Notably, we provide evidence for overexpression of the gene PTPRN2 in post-Neolithic revolution samples. PTPRN2 is a key regulator of insulin secretion, and our finding is compatible with hypoinsulinism in pre-Neolithic revolution hunter-gatherers. Additionally, we observe methylation changes in the genes EIF2AK4 and SLC2A5, which provide further evidence to metabolic adaptations to a changing diet during the Neolithic transition. RoAM offers powerful algorithms that position it as a key asset for researchers seeking to identify evolutionary regulatory changes through the lens of paleoepigenetics.

evolutionary biology↗

bioRxiv2023

Improved detection of methylation in ancient DNA

Reconstructing premortem DNA methylation levels in ancient DNA (aDNA) has led to breakthrough studies such as the prediction of anatomical features of the Denisovan, as well as the castration status of ancient horses. These studies relied on computationally inferring methylation levels from damage signals in naturally deaminated cytosines. Because of statistical constraints, this inference requires high-coverage sequencing, and is thus not only expensive but also restricted to samples with exceptional DNA preservation. Instead, a method to directly measure methylation levels in aDNA, as exists in modern DNA samples, would open the door to a more thorough and cost effective ability to study ancient DNA methylation. We have tested two methods for direct methylation measurement developed for modern DNA based on either bisulfite or enzymatic methylation treatments. We find that both methods preserve sufficient DNA yields to allow for methylation measurement. Bisulfite treatment, combined with a single stranded library preparation, shows the least reduction in DNA yields compared to no methylation treatment, as well as the least biases during methylation conversion. In addition, we show that applying bisulfite treatment to [~]0.4-fold coverage sample provides a methylation signal that is comparable to, or even better, than the computationally inferred one. We thus present a method to directly measure methylation in ancient DNA that is cost effective and can be used on a wide variety of ancient samples.

genomics↗

bioRxiv2017

Recent Regulatory Changes Shaped the Human Facial and Vocal Anatomy

SummaryRegulatory changes are broadly accepted as key drivers of phenotypic divergence. However, identifying regulatory changes that underlie human-specific traits has proven very challenging. Here, we use 63 DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes affecting the face and vocal tract went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-affecting 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.View Full Text

evolutionary biology↗