scholarly journals Interaction between Selection and Biased Gene Conversion in Mammalian Protein-Coding Sequence Evolution Revealed by a Phylogenetic Covariance Analysis

2012 ◽  
Vol 30 (2) ◽  
pp. 356-368 ◽  
Author(s):  
N. Lartillot
2015 ◽  
Vol 112 (7) ◽  
pp. 2109-2114 ◽  
Author(s):  
Barbara Arbeithuber ◽  
Andrea J. Betancourt ◽  
Thomas Ebner ◽  
Irene Tiemann-Boege

Meiosis is a potentially important source of germline mutations, as sites of meiotic recombination experience recurrent double-strand breaks (DSBs). However, evidence for a local mutagenic effect of recombination from population sequence data has been equivocal, likely because mutation is only one of several forces shaping sequence variation. By sequencing large numbers of single crossover molecules obtained from human sperm for two recombination hotspots, we find direct evidence that recombination is mutagenic: Crossovers carry more de novo mutations than nonrecombinant DNA molecules analyzed for the same donors and hotspots. The observed mutations were primarily CG to TA transitions, with a higher frequency of transitions at CpG than non-CpGs sites. This enrichment of mutations at CpG sites at hotspots could predominate in methylated regions involving frequent single-stranded DNA processing as part of DSB repair. In addition, our data set provides evidence that GC alleles are preferentially transmitted during crossing over, opposing mutation, and shows that GC-biased gene conversion (gBGC) predominates over mutation in the sequence evolution of hotspots. These findings are consistent with the idea that gBGC could be an adaptation to counteract the mutational load of recombination.


PLoS Genetics ◽  
2008 ◽  
Vol 4 (11) ◽  
pp. e1000250 ◽  
Author(s):  
Tobias Warnecke ◽  
Nizar N. Batada ◽  
Laurence D. Hurst

Author(s):  
Loïc Pellissier ◽  
Anna Kostikova ◽  
Glenn Litsios ◽  
Nicolas Salamin ◽  
Nadir Alvarez

Author(s):  
Yichen Dai ◽  
Sonia Trigueros ◽  
Peter W. H. Holland

AbstractGerbils are a subfamily of rodents living in arid regions of Asia and Africa. Recent studies have shown that several gerbil species have unusual amino acid changes in the PDX1 protein, a homeodomain transcription factor essential for pancreatic development and β-cell function. These changes were linked to strong GC-bias in the genome that may be caused by GC-biased gene conversion, and it has been hypothesized that this caused accumulation of deleterious changes. Here we use two approaches to examine if the unusual changes are adaptive or deleterious. First, we compare PDX1 protein sequences between 38 rodents to test for association with habitat. We show the PDX1 homeodomain is almost totally conserved in rodents, apart from gerbils, regardless of habitat. Second, we use ectopic gene overexpression and gene editing in cell culture to compare functional properties of PDX1 proteins. We show that the divergent gerbil PDX1 protein inefficiently binds an insulin gene promoter and ineffectively regulates insulin expression in response to high glucose in rat cells. The protein has, however, retained the ability to regulate some other β-cell genes. We suggest that during the evolution of gerbils, the selection-blind process of biased gene conversion pushed fixation of mutations adversely affecting function of a normally conserved homeodomain protein. We argue these changes were not entirely adaptive and may be associated with metabolic disorders in gerbil species on high carbohydrate diets. This unusual pattern of molecular evolution could have had a constraining effect on habitat and diet choice in the gerbil lineage.


2013 ◽  
Vol 94 (7) ◽  
pp. 1486-1495 ◽  
Author(s):  
Graham J. Belsham

The foot-and-mouth disease virus (FMDV) Leader (L) protein is produced in two forms, Lab and Lb, differing only at their amino-termini, due to the use of separate initiation codons, usually 84 nt apart. It has been shown previously, and confirmed here, that precise deletion of the Lab coding sequence is lethal for the virus, whereas loss of the Lb coding sequence results in a virus that is viable in BHK cells. In addition, it is now shown that deletion of the ‘spacer’ region between these two initiation codons can be tolerated. Growth of the virus precisely lacking just the Lb coding sequence resulted in a previously undetected accumulation of frameshift mutations within the ‘spacer’ region. These mutations block the inappropriate fusion of amino acid sequences to the amino-terminus of the capsid protein precursor. Modification, by site-directed mutagenesis, of the Lab initiation codon, in the context of the virus lacking the Lb coding region, was also tolerated by the virus within BHK cells. However, precise loss of the Lb coding sequence alone blocked FMDV replication in primary bovine thyroid cells. Thus, the requirement for the Leader protein coding sequences is highly dependent on the nature and extent of the residual Leader protein sequences and on the host cell system used. FMDVs precisely lacking Lb and with the Lab initiation codon modified may represent safer seed viruses for vaccine production.


Gene ◽  
2010 ◽  
Vol 463 (1-2) ◽  
pp. 49-55 ◽  
Author(s):  
Yvonne Döring ◽  
Ulrich Zechner ◽  
Christian Roos ◽  
David Rosenkranz ◽  
Hans Zischler ◽  
...  

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