A genome alignment of 120 mammals highlights ultraconserved element variability and placenta-associated enhancers

Abstract

Background Multiple alignments of mammalian genomes have been the basis of many comparative genomic studies aiming at annotating genes, detecting regions under evolutionary constraint, and studying genome evolution. A key factor that affects the power of comparative analyses is the number of species included in a genome alignment. Results To utilize the increased number of sequenced genomes and to provide an accessible resource for genomic studies, we generated a mammalian genome alignment comprising 120 species. We used this alignment and the CESAR method to provide protein-coding gene annotations for 119 non-human mammals. Furthermore, we illustrate the utility of this alignment by 2 exemplary analyses. First, we quantified how variable ultraconserved elements (UCEs) are among placental mammals. Leveraging the high taxonomic coverage in our alignment, we estimate that UCEs contain on average 4.7%–15.6% variable alignment columns. Furthermore, we show that the center regions of UCEs are generally most constrained. Second, we identified enhancer sequences that are only conserved in placental mammals. We found that these enhancers are significantly associated with placenta-related genes, suggesting that some of these enhancers may be involved in the evolution of placental mammal-specific aspects of the placenta. Conclusion The 120-mammal alignment and all other data are available for analysis and visualization in a genome browser at https://genome-public.pks.mpg.de/and for download at https://bds.mpi-cbg.de/hillerlab/120MammalAlignment/.

Six reference-quality genomes reveal evolution of bat adaptations

“…Genes showing evidence of positive selection were subsequently explored using protein structure prediction and modelling methods ( Supplementary Data 3). To systematically screen for gene losses, we used a previously developed approach 53 (Supplementary Note 4.5), and required that less than 80% of the ORF was intact in all six bats, excluding genes classified as lost in more than 20% of non-Chiroptera Laurasiatherian mammals contained in our 120-mammal multiple genome alignment 88 (Supplementary Note 4.5). We confirmed the presence of inactivating mutations in independently sequenced bat species.…”

“…4 5 6 7 8 9 10 12 14 16 18 20 22 24 26 28Presence of 197 non-exonic ultraconserved elements Miniopterus (Eckalbar et al 2016) 3 20 align at ≥ 85% identity to the human sequence. UCEs are highly conserved among mammals 88 and are expected to be present in complete assemblies. Bar charts show the number of detected UCEs that align at these stringent parameters.…”

Convergent losses of TLR5 suggest altered extracellular flagellin detection in four mammalian lineages

“…We applied a previously developed approach (Sharma, et al 2018a) to screen for geneinactivating mutations in TLR5 using a genome alignment of 120 placental mammals ( Supplementary Table 1) (Hecker, et al 2020). This screen revealed that the single coding exon of TLR5 exhibits stop codon mutations, smaller frameshifting insertions or deletions, or larger deletions in the genome assemblies of 17 species belonging to 14 distinct lineages (gorilla, orangutan, guinea pig, rabbit, pig, alpaca, Yangtze river dolphin, bighorn sheep, Weddell seal, Hawaiian monk seal, walrus, Malayan and Chinese pangolins, little brown bat, elephant, armadillo).…”

“…Since the two TLR5 transcripts in human GENCODE version 32 (Harrow, et al 2012) annotate an identical single coding exon and only differ in 5' UTR exons, we focused on this single coding exon. We used human as the reference species and initially considered a total of 119 non-human mammals that are part of a 120-mammal genome alignment (Hecker, et al 2020). The TLR5 sequence provided by this alignment was re-aligned with CESAR (Codon Exon Structure Aware Realigner) (Sharma, et al 2016;) to avoid spurious frameshifts due to alignment ambiguities.…”

Demographic history, cold adaptation, and recent NRAP recurrent convergent evolution at amino acid residue 100 in the world northernmost cattle from Russia

“…little brown bat and other hibernating bats and mouse lemur or enter seasonal torpor e.g., cape golden mole and tree shrew. Our statistical analysis using phylogenetic logistic regression(65) considering phylogeny of the 113 species from nine mammalian orders(66) shows phylogeny-independent significant correlation (R 2 0.77, p-value = 2.72e-06, alpha 0.00011) between the presence of the glutamine (Gln, Q) variant and cold adaptation, hibernation or ability to enter torpor…”