Scattering of genes from evolutionary breakpoint region due to chromosomal rearrangements

Lemaitre et al., (2009) define Evolutionary Breakpoint Regions (EBRs) as those genomic regions that have undergone at least one structural change that results in an altered karyotype between lineages. Characteristic features of EBRs have been analyzed using large-scale datasets to identify the prevalence of repeat regions, GC features, and epigenetic attributes associated with EBRs. Most changes in the gene order occur due to the chromosomal rearrangements that occur at the EBR loci. In addition to these changes in gene order, it has been proposed that gene loss can occur at these loci. For instance, the loss of approximately ~2000 genes is thought to have occurred in the ancestor of all birds. A vast majority of these gene loss events are proposed to coincide with EBRs. However, the challenges involved in sequencing and assembling the EBR regions have made it challenging to verify the validity of these claims. 

Similar to birds, the evolution of EBRs in rodent genomes has proved difficult to analyze and interpret. A recent study by Shinde et al. explores the EBR corresponding to the human chr7p13 in rodents and marsupials by a careful comparison of gene orders in several closely related species. Interestingly, they find that the same region has undergone rearrangement in both rodents and marsupials. However, the result of the rearrangement is slightly different in the two groups. While in rodents, both the STK17A and COA1/MITRAC15 genes are likely lost, the STK17A gene is retained after the rearrangement in marsupial species. 

The study is not entirely focused on the EBR though. Shinde et al. investigate the evolutionary history of the COA1 gene in various vertebrate species, more than 300 by their count. Recurrent loss of this gene is noted in galliform birds, several rodent species, and cheetah. Functional studies have implicated a role for COA1/MITRAC15 in promoting mitochondrial translation and complex I and IV biogenesis (Wang et al., 2020). Although COA1/MITRAC15 gene is widely conserved among vertebrate species, knockout studies exhibit a mild effect on function and can easily be compensated by overexpression of other genes (Pierrel et al., 2007; Hess et al., 2009). However, the prevalence of positive selection in primates suggests that the COA1/MITRAC15 can contribute to adaptation in the OXPHOS pathway (Van Der Lee et al., 2017). The loss of this gene following relaxed selection in the cheetah, Galliform birds, and several rodent species provides an example of gene dispensability in the OXPHOS pathway.

Salient features:

1.     Verification of the base-pair level changes leading to gene loss utilizes genome sequencing reads and transcriptomes.

2.   Several precautions based on the 5-step procedure proposed recently by Sharma et al., 2020 ensure gene loss validity.

3.     The timing of gene loss is estimated based on the widely used method proposed by Meredith et al. (Meredith et al., 2009). Signatures of relaxed selection characterized using the latest methods implemented in the HyPhy package and the models available in codeml.

4.    The role of evolutionary breakpoint regions (EBR) in gene loss is explored by investigating gene loss across multiple rodent species. Genomic regions that have translocated to different chromosomes after the rearrangement are studied in detail by comparing several pre-CR and post-CR species.

Novelty:

1. This study is probably the first report documenting the loss of a known oncogene in birds and might help understand the lower prevalence of cancer in birds than mammals.
2. Shinde et al., identify the origin of novel isoforms of COA1/MITRAC15 in Carnivore species through alternative splicing.

After two rounds of review, this manuscript is finally published in the journal Scientific Reports with the title "Recurrent erosion of COA1/MITRAC15 exemplifies conditional gene dispensability in oxidative phosphorylation". For any press releases or promotions, please note that the correct citation of the journal is “Scientific Reports” not “Nature Scientific Reports”.

References

 Hess, D. C. et al. (2009) ‘Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis’, PLoS Genetics. Edited by S. K. Kim, 5(3), p. e1000407. doi: 10.1371/journal.pgen.1000407.

Van Der Lee, R. et al. (2017) ‘Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts’, Nucleic Acids Research, 45(18), pp. 10634–10648. doi: 10.1093/nar/gkx704.

Meredith, R. W. et al. (2009) ‘Molecular decay of the tooth gene enamelin (ENAM) mirrors the loss of enamel in the fossil record of placental mammals’, PLoS Genetics, 5(9). doi: 10.1371/journal.pgen.1000634.

Pierrel, F. et al. (2007) ‘Coa1 links the Mss51 post-translational function to Cox1 cofactor insertion in cytochrome c oxidase assembly’, EMBO Journal, 26(20), pp. 4335–4346. doi: 10.1038/sj.emboj.7601861.

Sharma, S. et al. (2020) ‘Evidence for the loss of plasminogen receptor KT gene in chicken’, Immunogenetics, 72(9–10), pp. 507–515. doi: 10.1007/s00251-020-01186-2.

Wang, C. et al. (2020) ‘MITRAC15/COA1 promotes mitochondrial translation in a ND2 ribosome–nascent chain complex’, EMBO reports, 21(1). doi: 10.15252/embr.201948833.