Comparative transcriptome in large-scale human and cattle populations

Abstract

Background Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes. Results Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues. Conclusions In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.

A Multi-Tissue Gene Expression Atlas of Water Buffalo (Bubalus bubalis) Reveals Transcriptome Conservation between Buffalo and Cattle

“…Firstly, the correlation of the numbers of genes expressed in each tissue between the two species is 0.59, which was consistent with the findings of a previous comparative transcriptome study in cattle and humans [23]. The correlation in expression patterns within the same tissue between the two species was much higher than that within the same species in different tissues, as previously reported [23]. This finding further confirmed the conservation of tissue expression patterns between species [29].…”

“…Buffalo and cattle exhibited conservation in their overall expression patterns, TSGs, and HKGs. Firstly, the correlation of the numbers of genes expressed in each tissue between the two species is 0.59, which was consistent with the findings of a previous comparative transcriptome study in cattle and humans [23]. The correlation in expression patterns within the same tissue between the two species was much higher than that within the same species in different tissues, as previously reported [23].…”

“…We used the function IntegrateData in the R package Seurat [ 22 ] to combine gene expression datasets of buffalo and cattle, following the approach presented in a comparative transcriptome study between humans and cattle [ 23 ]. This methodology not only corrects for technical variations but also aligns the shared gene expression features across the datasets [ 22 ].…”

Learning functional conservation between pig and human to decipher evolutionary mechanisms underlying gene expression and complex trait

“…5a; Supplementary Figs. 5 and 6 ), which suggests that regulatory variants are functionally conserved between species 35,36 . Of note, sQTLs showed a higher DeepGCF score than eQTLs in both species (Mann–Whitney U test P < 1e-8), probably due to their larger impacts on the transcriptome function (underlying a stronger purifying selection).…”

FarmGTEx TWAS-server: an interactive web server for customized TWAS analysis in both human and farm animals

“…In addition, translating genetic findings across species is also important in the field of evolution, biology, and genetics. For instance, previous studies demonstrated the conserved functional impacts of orthologous variants on gene expression and complex traits between livestock and humans (23)(24)(25)(26)(27)(28). Liang et al (29) also proposed polygenic transcriptomic risk scores (PTRS), which paved the way to translate polygenic signals across human ancestry groups.…”