*3.3. uATGs—Number and Conservation*

Among human ABCA genes, there are two (17%; *ABCA5* and *ABCA13*) having no uATG; the others (83%) have at least 1 uATG, ranging from 1 to 14 uATGs (*ABCA10*). The median number of uATGs in the ABCA subfamily was computed to be 2 (average is 3 and mode 1), again showing a great variability among individual members. In total, 37 uATGs were found in the subfamily. The median value of uATG conservation was 1 (on a scale of 0–5), minimum 0 and maximum 5. 49% of the uATGs had a conservation value more than 1, that is, conserved in at least one other vertebrate subgroup except primates. Generally, uATGs and uORFs decrease mRNA translation efficiency and may be considered strong negative translational regulatory signals [28–30]. One of the approaches to address the issue of the functional significance of uATGs is to examine the evolutionary conservation of these

triplets. Churbanov et al. [31] reported that the ATG triplet is conserved to a significantly greater extent than any of the other 63 nucleotide triplets in 5′UTRs of mammalian cDNAs, but not in 3′UTRs or coding sequences, by comparing sequences of human, mouse, and rat orthologous genes. Moreover, they observed that 5′UTRs are significantly depleted in overall ATG content. Approximately 25% of the 5 ′UTRs analyzed in their work contained at least one conserved uATG. In a similar study performed by Iacono and colleagues [32], uATGs and uORFs were detected in about 44% of 5′UTRs. They also concluded that both uATGs and uORFs are less frequent than expected by chance in 5′UTRs. 24% and 38% of human uATGs and uORFs were evolutionary conserved in all three taxa considered (human, mouse, and rat), respectively. Of the population of human and mouse mRNAs with long 5′UTRs (>60 bases), approximately 55% had at least one uAUG, with about 25% having one or more uORFs (average about 1.9 uORFs) [33]. We found that 5′UTRs of ABCA genes contain above-average numbers of uATGs as well as conserved ones. Approximately half of all uATGs in ABCA are conserved not only within primates, but also in other vertebrate subgroups. Considering this high level of conservation among uATGs, they probably play important biological roles in this subfamily.
