Working papers

Sexually antagonistic selection and sex chromosome evolution in Stickleback

January 25, 2017

Submission to the 2017 Society for Molecular Biology & Evolution meeting at Austin, TX.

Changde Cheng, Andrius J. Dagilis, Jason M. Sardell, Asano Ishikawa, Jun Kitano, Matthew P. Josephson, Catherine L. Peichel, Mark Kirkpatrick

Why do females and males differ (Darwin 1871)? What are the evolutionary forces behind the differences between the sexes?

Sexually antagonistic selection (“SA selection”), which increases the fitness of an allele in one sex and decreases it in the other (Fisher 1958, Arnqvist and Rowe 2005), is a top candidate. SA selection is also thought to be important in the evolution of sex chromosomes by favoring reduced recombination between sex-determining loci and loci under SA selection (van Doorn and Kirkpatrick 2007).

Despite its theoretical importance, we know little about the strength and genomic targets of SA selection in natural populations. SA selection can be widespread in the genome. Eight percent of genes have been estimated to be under SA selection in Drosophila by measuring the fitness of females and males in the lab (Innocenti and Morrow 2010). However, there is little understanding of the strengths and targets of SA selection in natural populations (Cheng and Kirkpatrick 2016).

Sex chromosomes offer unique opportunities to advance our understanding of SA selection. Theory predicts genes under SA selection should be enriched on sex chromosomes (Rice 1992). Furthermore, SA selection is predicted to cause the evolution of reduced recombination between X and Y (or Z and W) by chromosomal rearrangements (Charlesworth and Charlesworth 1980).

The young and still recombining sex chromosomes in Japan Sea stickleback (Gasterosteus nipponicus) provide a rare opportunity to study SA selection. We sequenced and phased whole sex chromosomes by analyzing genetic inheritance in family quartets. We aimed to look for footprints of SA selection by detecting regions of significantly elevated divergence between X and Y chromosomes. We estimated the strength and targets of SA selection by fitting a population genetics model to the data. We investigated the phenotypic effects of loci under SA selection by integrating results from previous QTL studies. Our study is among the first to reveal the nature of the forces acting in the earliest stages of sex chromosome evolution using genomic data. Our work will provide insight into evolutionary forces that establish genes with conflicting effects in females and males, which are detrimental to health, including our own species.

Innate T cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation.

February 1, 2022

Among patients hospitalized for cardiac arrest (CA), most deaths are driven by neurological injury. Despite its clinical importance, there are no effective pharmacological therapies targeting post-CA neurological injury. In single-cell RNA-sequencing of peripheral blood mononuclear cells …

Tomoyoshi Tamura#, Kei Hayashida#, Kohei Ikeda#, Changde Cheng#, Louis T. Merriam, Jack Varon, Jiyoung Choi, Aidan M. Cullen, Jingyu Guo, Benjamin A. Olenchock, Mayra A. Pinilla-Vera, Ana B. Villasenor-Altamirano, Reshmi Manandhar, Muhammad Dawood Amir Sheikh, Peter C. Hou, Patrick R. Lawler, William M. Oldham, Raghu R. Seethala, Immunology of Cardiac Arrest Network (I-CAN)9, Rebecca M. Baron, Erin A. Bohula, David A. Morrow, Alexandra Weissman, Xiang Chen, Michael B. Brenner, Fumito Ichinose*, Edy Y. Kim*, Immunology of Cardiac Arrest Network (I-CAN); Innate T cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation

Genomic analysis of bilateral Wilms tumor: a Children’s Oncology Group and St. Jude Children’s Research Hospital study

May 22, 2022

We aimed to determine the landscape of genetic and epigenetic predisposition for synchronous bilateral Wilms tumor (BWT) formation using samples from 70 patients with BWT from the Children’s Oncology Group and St. Jude Children’s Research Hospital. We performed whole exome or whole genome sequencing, total-strand RNA-seq, and 850K MethylationEPIC Beadchip analysis. We found that 41% of patients evaluated had germline genetic variants in Wilms tumor or pediatric cancer predisposition genes, with WT1 (16%), NYNRIN (6.6%), TRIM28 (5%) and the BRCA-related genes (5%) BRCA-1, BRCA-2, and PALB2 being the most common. WT1 germline variants were strongly associated with paternal uniparental disomy overlapping the 11p15.5 locus and 11p13/WT1 locus in tumor samples and subsequent somatic CTNNB1 variants. Somatic variants were almost never shared between paired synchronous BWT. However, 11p15.5 status (loss of imprinting, loss of heterozygosity, retention of imprinting) was shared among paired synchronous BWT in all but one case. The predominant methods of predisposition for BWT formation are germline genetic variants or post-zygotic epigenetic hypermethylation at the 11p15.5 ICR1 locus (loss of imprinting). 11p15.5 status correlates with an overall methylation profile in BWT.

Andrew J Murphy#, *, Changde Cheng*, Justin Williams, Timothy I Shaw, Emilia M Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay Renfro, Brett Tornwall, Vicki Huff, Andy Hong, Elizabeth Mullen, Brian Crompton, Jim Geller, Peter Ehrlich, Heather Mulder, Janet Partridge, Alfonso Fernandez Gonzalez, Hyea Jin Gil, Carolyn Jablonowski, Andrew Fleming, Prahalathan Pichavaram, John Easton, Kim Nichols, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P Zambetti, Zhaoming Wang, Andrew M Davidoff, Xiang Chen#Genomic analysis of bilateral Wilms tumor: a Children’s Oncology Group and St. Jude Children’s Research Hospital study

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