fem and csd. a drama of the paralogs.

    Gene duplication events represent  the possibility for major evolutionary innovation, and possibly hold the key to the evolution of complex molecular and phenotypic regimes.  To this end, neofunctionalization, that is the processes whereby a newly duplicated gene gains a function not present in the progenitor gene, and its real-world representatives (ie newly paralogous genes) provide an interesting avenue for molecular and evolutionary study.  De and Babu (2010) found that, in areas surrounding gene duplication events (and indels etc), sequence divergence is much higher than surrounding genomic divergence levels (likely due to the mechanics associated with DNA break, repair and template-dependent DNA synthesis), possibly fueling this exaptation of duplicated genes.  Furthermore, due to the possibly relaxed selective pressures on duplicated genes, such genes might be better suited to explore sequence space through neutral or nearly-neutral mutations, providing an exploratory power not available to the initial (parent) gene, however it may also be argued that evolutionary interference or genetic "hitchhiking" (often associated with such gene duplications and diversifications) might confound evolutionary studies. 
   
     For these reasons, Hasselmann et al studied the duplication of a gene (complimentary sex determiner--csd) involved in the Hymenopteran sex-determination cascade (and the novel functions therein), in an effort to better understand the shifting of selective constraints and molecular mechanisms associated with such duplication and whether the parent gene's evolutionary patterns are affected by the presence of this ontologically similar paralog.  csd is a particularly interesting candidate for evolutionary studies as it is (almost certainly) the product of the duplication of the sex-determining tra Hymenopteran ortholog (in dipterans and other insects) feminizer (fem), is held under a heterozygous advantage due to its specific ontology, and is relatively recently diverged from fem (between ~70-10mya).

    The authors found a reduced n/s ratio in Apis lineages which experienced such gene duplication when contrasted to related non-Apis lineages which did not experience the duplication of fem.  This might imply increased purifying selection associated with the gene duplication event at the fem locus.  Alternatively, they speculate that this could be due to increased synonymous substitution rate in the lineage of Apis fem, possibly resulting from an increased mutation rate (associated with said duplication).   In an effort to test these two hypotheses the authors applied a "relative rate test" to identify accelerations of synonymous substitution rates in the Apis tree branches as an indicator for increased mutation rates--which found no such increased mutation rates.  The authors also found one protein-binding region of fem which exhibited a low dn/ds ratio between Apis and non-Apis and high dn/ds in non-Apis comparisons indicating lineage-specific evolutionary constraints.
   
    Through this analysis the authors demonstrate that the origin of the fem paralog csd led to increased evolutionary constraints on the feminizer gene related to sex-determination in social Hymenopterans.  They demonstrate a marked decrease in the dn/ds rates associated with Apis lineages when compared to non-Apis lineages--ie after vs before csd origin--indicating a functional interference in evolutionary rates associated with the origin of csd.  They also conclude that these similar dn/ds values between Apis fem and csd are not the product of genetic linkage, but some other functional interference, possibly related to the balancing selection associated with complimentary sex determination (sex determination mechanism in Hymenoptera wherein homo or hemizygous individuals become one sex--male-- and heterozygous individuals become another--associated with haplodiploidy).  Their results also support other authors   An interesting, if not somewhat incomplete-feeling, study.




-Hasselmann,, Lechner, Schulte and Beye (2010). Origin of a function by tandem gene duplication limits the evolutionary capability of its sister copy. PNAS 107 (30): 13378-13383
-De and Babu (2010). A time-invariant principle of genome evolution. PNAS 107 (29): 13004-13010