Why are protein-coding regions rich in GC?

Question

I have been searching for an answer for this question and have some possible solutions, but I am not sure. GC regions are more stable as there are 3 hydrogen bonds instead of 2 with AT, however I am not sure if this would influence the number of protein-coding genes in GC regions? Protein-coding regions would have to be less condensed than noncoding regions so transcription factors could access them. Would a high GC content influence this as well?

Answer 1

Transcription factors generally bind to promoters, enhancers, silencers, and other regulatory regions that lie outside coding regions, through there are "duons" which code for amino acids and also bind TFs to regulatory effect. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967546/

One paper suggests GC content helps balance recombination events with genetic stability, and so there may be an evolutionary benefit from organisms that undergo sexual reproduction having GC-rich coding regions. https://www.frontiersin.org/articles/10.3389/fpls.2016.01433/full

In eukaryotes, meiotic exchange of genetic information, or recombination, between homologous chromosomes is a critical step in generating genetic diversity required for adaptation. Recombination is also a crucial tool in plant improvement efforts. Local genome architecture is sculpted by the recombination process, and genome architecture, in turn, drives recombination. This interplay helps to create variability in genomic space, defining relatively stable and plastic genomic regions. This fluctuation in genomic stability is critical for balancing adaptation and stability on the phenotypic level.

Recombination has direct implications for GC patterns and vice versa. GC content refers to the percentage of guanine and cytosine bases in a DNA sequence, as opposed to adenine and thymidine bases. There have been many studies substantiating the positive correlation between recombination and GC content (Ikemura and Wada, 1991; Eyre-Walker, 1993; Fullerton et al., 2001; Galtier et al., 2001; Marais et al., 2001; Duret and Arndt, 2008; Haudry et al., 2008; Escobar et al., 2010; Muyle et al., 2011). Crossovers have been found to be correlated with high GC content in rat, mouse, human, zebrafish, bee, and maize at a broad scale (Jensen-Seaman et al., 2004; Beye et al., 2006; Gore et al., 2009; Backstrom et al., 2010; Giraut et al., 2011), while other studies detected strong correlation only at a fine scale (∼5 kb for yeast, ∼15–128 kb for human) and rather weak correlation at a broad scale (∼30 kb for yeast, ∼1 Mb for human; Gerton et al., 2000; Myers et al., 2006; Marsolier-Kergoat and Yeramian, 2009).

GC-richness may offer the ability for organisms to create offspring that evolve to changes to the environment and fend off parasites, while also being viable enough to procreate, themselves.