Biology subjects

Schraiber, J.

Publications and source records attributed to Schraiber, J..

5 recordsLinked to original sources

bioRxiv2023

The landscape of tolerated genetic variation in humans and primates

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human. We show that these variants can be inferred to have non-deleterious effects in human based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases. One Sentence SummaryDeep learning classifier trained on 4.3 million common primate missense variants predicts variant pathogenicity in humans.

genomics↗

bioRxiv2021

Convergent selection on juvenile hormone signaling is associated with the evolution of eusociality in bees

Sweat bees have repeatedly gained and lost eusociality, a transition from individual to group reproduction. Here, we generate chromosome-length genome assemblies for 17 species and identify genomic signatures of evolutionary trade-offs associated with transitions between social and solitary living. Both young genes and regulatory regions show enrichment for these molecular patterns. We also identify loci that show evidence of complementary signals of positive and relaxed selection linked specifically to the convergent gains and losses of eusociality in sweat bees. This includes two proteins that bind and transport juvenile hormone (JH) - a key regulator of insect development and reproduction. We find one of these JH binding proteins is primarily expressed in subperineurial glial cells that form the insect blood-brain barrier and that brain levels of JH vary by sociality. Our findings are consistent with a role of JH in modulating social behavior and suggest eusocial evolution was facilitated by alteration of the proteins that bind and transport JH, revealing how an ancestral, developmental hormone may have been co-opted during one of lifes major transitions. More broadly, our results highlight how trade-offs have structured the molecular basis of eusociality in these bees and demonstrate how both directional selection and release from constraint can shape trait evolution.

evolutionary biology↗

bioRxiv2020

AN ADMIXTURE SIGNAL IN ARMENIANS AROUND THE END OF THE BRONZE AGE REVEALS WIDESPREAD POPULATION MOVEMENT ACROSS THE MIDDLE EAST

The Armenians, a population inhabiting the region in West Asia known as the Armenian Highland, has been argued to show a remarkable degree of population continuity since the Early Neolithic. Here we test the degree of continuity of this population as well as its plausible origin, by collating modern and ancient genomic data, and adding a number of novel contemporary genomes. We show that Armenians have indeed remained unadmixed through the Neolithic and at least until the first part of the Bronze Age, and fail to find any support for historical suggestions by Herodotus of an input from the Balkans. However, we do detect a genetic input of Sardinian-like ancestry during or just after the Middle-Late Bronze Age. A similar input at approximately the same time was detected in East Africa, suggesting large-scale movement both North and South of the Middle East. Whether such large-scale population movement was a result of climatic or cultural changes is unclear, as well as the true source of gene flow remains an open question that needs to be addressed in future ancient DNA studies.

genomics↗

bioRxiv2018

Spectrum of Neandertal introgression across modern-day humans indicates multiple episodes of human-Neandertal interbreeding

1Neandertals and anatomically modern humans overlapped geographically for a period of over 30,000 years following human migration out of Africa. During this period, Neandertals and humans interbred, as evidenced by Neandertal portions of the genome carried by non-African individuals today. A key observation is that the proportion of Neandertal ancestry is [~]12-20% higher in East Asian individuals relative to European individuals. Here, we explore various demographic models that could explain this observation. These include distinguishing between a single admixture event and multiple Neandertal contributions to either population, and the hypothesis that reduced Neandertal ancestry in modern Europeans resulted from more recent admixture with a ghost population that lacked a Neandertal ancestry component (the \"dilution\" hypothesis). In order to summarize the asymmetric pattern of Neandertal allele frequencies, we compile the joint fragment frequency spectrum (FFS) of European and East Asian Neandertal fragments and compare it to both analytical theory and data simulated under various models of admixture. Using maximum likelihood and machine learning, we found that a simple model of a single admixture does not fit the empirical data, and instead favor a model of multiple episodes of gene flow into both European and East Asian populations. These findings indicate more long-term, complex interaction between humans and Neandertals than previously appreciated.

evolutionary biology↗

bioRxiv2017

Assessing the relationship of ancient and modern populations

Genetic material sequenced from ancient samples is revolutionizing our understanding of the recent evolutionary past. However, ancient DNA is often degraded, resulting in low coverage, error-prone sequencing. Several solutions exist to this problem, ranging from simple approach such as selecting a read at random for each site to more complicated approaches involving genotype likelihoods. In this work, we present a novel method for assessing the relationship of an ancient sample with a modern population while accounting for sequencing error and post-mortem damage by analyzing raw read from multiple ancient individuals simultaneously. We show that when analyzing SNP data, it is better to sequence more ancient samples to low coverage: two samples sequenced to 0.5x coverage provide better resolution than a single sample sequenced to 2x coverage. We also examined the power to detect whether an ancient sample is directly ancestral to a modern population, finding that with even a few high cover-age individuals, even ancient samples that are very slightly diverged from the modern population can be detected with ease. When we applied our approach to European samples, we found that no ancient samples represent direct ancestors of modern Europeans. We also found that, as shown previously, the most ancient Europeans appear to have had the smallest effective population sizes, indicating a role for agriculture in modern population growth.

evolutionary biology↗