Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations

Abstract

The transition from land to water in whales and dolphins (cetaceans) was accompanied by remarkable adaptations. To reveal genomic changes that occurred during this transition, we screened for protein-coding genes that were inactivated in the ancestral cetacean lineage. We found 85 gene losses. Some of these were likely beneficial for cetaceans, for example, by reducing the risk of thrombus formation during diving (F12 and KLKB1), erroneous DNA damage repair (POLM), and oxidative stress–induced lung inflammation (MAP3K19). Additional gene losses may reflect other diving-related adaptations, such as enhanced vasoconstriction during the diving response (mediated by SLC6A18) and altered pulmonary surfactant composition (SEC14L3), while loss of SLC4A9 relates to a reduced need for saliva. Last, loss of melatonin synthesis and receptor genes (AANAT, ASMT, and MTNR1A/B) may have been a precondition for adopting unihemispheric sleep. Our findings suggest that some genes lost in ancestral cetaceans were likely involved in adapting to a fully aquatic lifestyle.

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

“…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 we have previously shown that apparent gene-inactivating mutations can sometimes be sequencing or assembly errors (Hecker, et al 2017;Sharma, et al 2018b;Hecker, et al 2019a;Huelsmann, et al 2019), we carefully validated the correctness of all such putative mutations and performed additional analyses to establish which of these 17 species truly lost TLR5.…”

“…In general, loss of a gene can be due to relaxed selection to preserve its function or provide an evolutionary advantage (Albalat, et al 2016;Sharma, et al 2018a;Hecker, et al 2019b;Huelsmann, et al 2019). Interestingly, in humans, the TLR5 stop codon mutation is associated with both positive and negative consequences.…”

“…Gene-inactivating mutations that are shared between related species are strong evidence against assembly base errors and indicate that gene loss is fixed in the respective clade (Hecker, et al 2019b;Huelsmann, et al 2019;. Therefore, in addition to the 119 non-human mammals included in the 120-mammal genome alignment, we analyzed TLR5 in six additional mammals that are close sister species to TLR5-loss species (two river dolphins, two guinea pigs, tree pangolin and Antarctic fur seal; NCBI assembly accession numbers are listed in Supplementary Table 1).…”

Recapitulating evolutionary divergence in a singlecis-regulatory element is sufficient to cause expression changes of the lens geneTdrd7

“…Understanding the contribution of mutations in such genes or regulatory elements to the evolution of a trait requires an experimentallytractable system, such as the mouse, where specific mutations can be introduced and their effects quantified. Gene knockout studies in mice contributed to our understanding of the functional role of many genes naturally lost in a variety of mammalian species (39)(40)(41)(42)(43)(44)(45)(46). However, the effect of other, much more frequent genomic changes, such as amino-acid changing mutations in protein-coding sequences and sequence changes in regulatory elements has rarely been explored.…”

Loss of critical developmental and human disease-causing genes in 58 mammals

“…However, their overly inclusive approach predicted hundreds of gene losses per species across 62 mammals, of which only 21 total were reported, presumably because manual inspection found many loss predictions to 3 be spurious. Similar technique was used to further semi-manually annotate 85 gene losses in cetaceans [16]. Other computational approaches for gene annotation, like the Ensembl pipeline [17], combine ab initio predictions with protein sequence evidence [18] and with gene models inferred from RNA-seq data.…”