$ perl vert2.pl
ok 1 - same results
ok 2 - same results
ok 3 - same results
            (warning: too few iterations for a reliable count)
            (warning: too few iterations for a reliable count)
            (warning: too few iterations for a reliable count)
            (warning: too few iterations for a reliable count)
          Rate   seek    buk substr  slurp
seek   0.920/s     --   -61%   -84%   -88%
buk     2.36/s   157%     --   -58%   -69%
substr  5.66/s   515%   140%     --   -26%
slurp   7.69/s   736%   226%    36%     --
1..3

##</code><code>##

use strict;
use warnings;
use feature 'say';
use String::Random 'random_regex';
use Benchmark 'cmpthese';
use Test::More 'no_plan';

my $fn  = 'dna.txt';
my $POS = 10;

unless ( -e $fn ) {
    open my $fh, '>', $fn;
    print $fh random_regex( '[ACTG]{42}' ), "\n"
        for 1 .. 1e6;
}

is_deeply _seek(), _substr(), 'same results';
is_deeply slurp(), _substr(), 'same results';
is_deeply buk(),   _substr(), 'same results';

cmpthese( 3, {
    substr => \&_substr,
    seek   => \&_seek,
    buk    => \&buk,
    slurp  => \&slurp,
});


sub slurp {
    open my $fh, '<', $fn;
    my $s = do { local $/ = undef; <$fh> };
    my $count;
    $count-> { substr $s, $POS - 1 + 43 * $_, 1 }++
        for 0 .. length( $s ) / 43 - 1;
    return $count
}

sub buk {
    open my $fh, '<', $fn;
    my $buf = chr( 0 ) x 43;
    my $ref = \substr( $buf, $POS - 1, 1 );
    my $count;
    until ( eof $fh ) {
        substr( $buf, 0 ) = <$fh>;
        $count-> { $$ref }++
    }
    return $count
}

sub _seek {
    open my $fh, '<', $fn;
    my $L = length( <$fh> ) - 1;
    seek $fh, $POS - 1, 0;
    my $count;
    until ( eof $fh ) {
        $count-> { getc $fh }++;
        seek $fh, $L, 1
    }
    return $count
}

sub _substr {
    open my $fh, '<', $fn;
    my $count;
    $count-> { substr $_, $POS - 1, 1 }++
        while <$fh>;
    return $count
}

##</code><code>##

$ perl -v

This is perl 5, version 26, subversion 0 (v5.26.0) built for x86_64-linux-thread-multi
(with 1 registered patch, see perl -V for more detail)